Intermittent Strategy Research Articles

Characterization of Post Coronary Artery Bypass Grafting Atrial Fibrillation Patterns: Rationale and Design of an Investigator-Initiated Observational Study

New-onset postoperative atrial fibrillation (POAF) after cardiac surgery is associated with increased rates of adverse events (including mortality and stroke). Its incidence after coronary artery bypass grafting (CABG) is considered to be approximately 30 % and it is thought to be a transient condition. However, studies investigating POAF after CABG fail to provide appropriate data on incidence and arrhythmia patterns due to the use of intermittent rhythm detection strategies. These methods have a low sensitivity as compared to continuous monitoring. Subsequently, studies utilizing these techniques most likely do not identify all patients with arrhythmia and do not adequately demonstrate the long-term incidence of arrhythmia, which in turn may affect its association with adverse events. The CABG-AF study (German Clinical Trials Register Nr.: DRKS00018887) tests the hypothesis that the incidence of AF in the first 12 months after CABG is significantly underestimated. CABG-AF is an investigator-initiated multicenter, prospective, observational study in which 196 patients with no history of arrhythmia undergoing first-time CABG, receive an insertable cardiac monitor for continuous postoperative rhythm monitoring. The primary endpoint of the study is any episode of AF within the first 12 months after surgery. Secondary endpoints include AF burden, AF density and the ratio of silent to symptomatic AF episodes. Endpoints will be investigated by automatic and patient-initiated data transfers from the implanted device, by telephone interview of patients and by follow-up forms sent to patients by mail. The patients will be followed for a planned follow-up of 3 years. In conclusion, the CABG-AF study will provide information on the true incidence of AF after CABG as well as on the temporal patterns of the arrhythmia.

Synchronization of Euler-Lagrangian networks: a periodic intermittent dynamic event-triggered control strategy

In this paper, the synchronization problem of Euler–Lagrange networks is studied by designing periodic intermittent dynamic event-triggered control strategy. The synchronization of all agents is successfully realized by injecting negative comments into the discontinuous interval of the agents described by the Euler–Lagrange systems. Different from the traditional intermittent event-triggered control strategy, the control strategy proposed in this study introduces internal dynamic variables to expand the sampling interval of the event-triggered mechanism, thereby improving resource utilization efficiency. In addition, the event trigger instants of each agent are asynchronous. By using graph theory and Lyapunov method, the synchronization criteria of Euler–Lagrange networks are derived. The effectiveness of the proposed control scheme is verified by simulations for the Euler-Lagrangian network composed of six two-link rotating manipulators.

Biovalorization of lignin-derived substrates to vanillylamine via a self-sufficient amino donor and cofactor recycling whole-cell platform

Lignin valorization through bioconversion to high-value chemicals is crucial for sustainable bioprocessing. Vanillin (VN), a primary lignin derivative, can be transaminated into vanillylamine (VM), a key precursor for capsaicin and pharmaceuticals. This study established a novel self-sufficient redox-complementary whole-cell system, facilitating the recycling of L-alanine and cofactors for efficient VM biosynthesis. Ammonium formate (AF) was employed as amino donor and co-substrate. Recombinant E. coli strain, co-expressing ω-transaminase (CvTA), L-alanine dehydrogenase (ALD), and formate dehydrogenase (FDH), showed higher yield in shorter reaction time compared to the strain expressing only CvTA and ALD. Intermittent feeding strategy was developed to mitigate VN cytotoxicity problem and a remarkable yield of 97.3 ± 1.0% was achieved of VM from 60 mM VN under optimized biotransamination conditions (37 °C, pH 8.0, VN:AF = 1:5, and 1.5 mM NAD+). Notably, a double-plasmid E. coli recombinant harboring CvTA, ALD, FDH, and aromatic dioxygenase (ADO) was constructed to convert isoeugenol into VM with a 73.2 ± 1.1% yield. This efficient biotransamination platform not only offers a sustainable route to VM for capsaicin production but also promotes lignin valorization for a greener bioeconomy.

A Retrospective Analysis of Intravenous Push versus Extended Infusion Meropenem in Critically Ill Patients.

Meropenem is a broad-spectrum antibiotic used for the treatment of multi-drug-resistant infections. Due to its pharmacokinetic profile, meropenem's activity is optimized by maintaining a specific time the serum concentration remains above the minimum inhibitory concentration (MIC) via extended infusion (EI), continuous infusion, or intermittent infusion dosing strategies. The available literature varies regarding the superiority of these dosing strategies. This study's primary objective was to determine the difference in time to clinical stabilization between intravenous push (IVP) and EI administration. We performed a retrospective pilot cohort study of 100 critically ill patients who received meropenem by IVP (n = 50) or EI (n = 50) during their intensive care unit (ICU) admission. There was no statistically significant difference in the overall achievement of clinical stabilization between IVP and EI (48% vs. 44%, p = 0.17). However, the median time to clinical stability was shorter for the EI group (20.4 vs. 66.2 h, p = 0.01). EI administration was associated with shorter hospital (13 vs. 17 days; p = 0.05) and ICU (6 vs. 9 days; p = 0.02) lengths of stay. Although we did not find a statistically significant difference in the overall time to clinical stabilization, the results of this pilot study suggest that EI administration may produce quicker clinical resolutions than IVP.

Stochastic resetting can optimize the intermittent search strategy in a two-dimensional confined topography

Based on the intermittent two-state random walk model, by calculating and discussing the mean first capture time, the search efficiency of the intermittent search strategy in a two-dimensional confined topography in the absence and presence of stochastic resetting is studied. Results reveal that for the close target, the regular Brownian motion is the efficient search strategy, whereas, for the target far from the starting point, the typical intermittent search strategy with relocation times being power-law distributed turns out to be the advantageous one, and the search efficiency impressively enhances with the distance of the target from the starting point increasing. We demonstrate that though in the absence of stochastic resetting there does not exist a universal optimal search strategy in the confined topography, the introduction of stochastic resetting makes the Brownian motion surprisingly to be the universal optimal search process, and distinctly outperforms the ones without stochastic resetting.

Aperiodically Intermittent Event-Triggered Optimal Average Consensus for Nonlinear Multi-Agent Systems.

This article is concerned with average consensus of multi-agent systems via intermittent event-triggered strategy. First, a novel intermittent event-triggered condition is designed and the corresponding piecewise differential inequality for the condition is established. Using the established inequality, several criteria on average consensus are obtained. Second, the optimality has been investigated based on average consensus. The optimal intermittent event-triggered strategy in the sense of Nash equilibrium and corresponding local Hamilton-Jacobi-Bellman equation are derived. Third, the adaptive dynamic programming algorithm for the optimal strategy and its neural network implementation with actor-critic architecture are also given. Finally, two numerical examples are presented to show the feasibility and effectiveness of our strategies.

Generalized synchronization of two-layer networks based on intermittent control strategy

Generalized synchronization of two-layer networks based on intermittent control strategy

Meropenem pharmacokinetics in cerebrospinal fluid: comparing intermittent and continuous infusion strategies in critically ill patients-a prospective cohort study.

This study is registered with ClinicalTrials.gov as NCT04426383.

How the brain can be trained to achieve an intermittent control strategy for stabilizing quiet stance by means of reinforcement learning

The stabilization of human quiet stance is achieved by a combination of the intrinsic elastic properties of ankle muscles and an active closed-loop activation of the ankle muscles, driven by the delayed feedback of the ongoing sway angle and the corresponding angular velocity in a way of a delayed proportional (P) and derivative (D) feedback controller. It has been shown that the active component of the stabilization process is likely to operate in an intermittent manner rather than as a continuous controller: the switching policy is defined in the phase-plane, which is divided in dangerous and safe regions, separated by appropriate switching boundaries. When the state enters a dangerous region, the delayed PD control is activated, and it is switched off when it enters a safe region, leaving the system to evolve freely. In comparison with continuous feedback control, the intermittent mechanism is more robust and capable to better reproduce postural sway patterns in healthy people. However, the superior performance of the intermittent control paradigm as well as its biological plausibility, suggested by experimental evidence of the intermittent activation of the ankle muscles, leaves open the quest of a feasible learning process, by which the brain can identify the appropriate state-dependent switching policy and tune accordingly the P and D parameters. In this work, it is shown how such a goal can be achieved with a reinforcement motor learning paradigm, building upon the evidence that, in general, the basal ganglia are known to play a central role in reinforcement learning for action selection and, in particular, were found to be specifically involved in postural stabilization.

An output feedback method to polynomial stabilization of hybrid pantograph stochastic systems with aperiodic sampling

This paper focuses on the polynomial stabilization problem of hybrid pantograph stochastic systems (HPSSs) with aperiodic sampling in the presence of randomly occurring transmission delay. Firstly, a sufficient condition is provided to ensure the existence, uniqueness and boundedness of solution to such systems. Next, taking advantage of the Lyapunov stability theory and the comparison method, the criteria of pth moment polynomial stability are established for the HPSSs under the feedback control and aperiodic intermittent control strategy, respectively. Finally, the proposed theoretical results of two control methods are simultaneously validated through a numerical example.

Assessing the impacts of vaccination and viral evolution in contact networks

A key lesson learned with COVID-19 is that public health measures were very different from country to country. In this study, we provide an analysis of epidemic dynamics using three well-known stochastic network models—small-world networks (Watts–Strogatz), random networks (Erdös–Rényi), and scale-free networks (Barabási–Albert)—to assess the impact of different viral strains, lockdown strategies, and vaccination campaigns. We highlight the significant role of highly connected nodes in the spread of infections, particularly within Barabási–Albert networks. These networks experienced earlier and higher peaks in infection rates, but ultimately had the lowest total number of infections, indicating their rapid transmission dynamics. We also found that intermittent lockdown strategies, particularly those with 7-day intervals, effectively reduce the total number of infections, serving as viable alternatives to prolonged continuous lockdowns. When simulating vaccination campaigns, we observed a bimodal distribution leading to two distinct outcomes: pandemic contraction and pandemic expansion. For WS and ER networks, rapid mass vaccination campaigns significantly reduced infection rates compared to slower campaigns; however, for BA networks, differences between vaccination strategies were minimal. To account for the evolution of a virus into a more transmissible strain, we modeled vaccination scenarios that varied vaccine efficacy against the wild-type virus and noted a decline in this efficacy over time against a second variant. Our results showed that vaccination coverage above 40% significantly flattened infection peaks for the wild-type virus, while at least 80% coverage was required to similarly reduce peaks for variant 2. Furthermore, the effect of vaccine efficacy on reducing the peak of variant 2 infection was minimal. Although vaccination strategies targeting hub nodes in scale-free networks did not substantially reduce the total number of infections, they were effective in increasing the probability of preventing pandemic outbreaks. These findings underscore the need to consider the network structure for effective pandemic control.

Heat Transfer Performance and Operation Scheme of the Deeply Buried Pipe Energy Pile Group

This paper describes a study on the heat transfer properties of the deeply buried pipeline energy pile group, which is an efficient and convenient geothermal development technology. Through in situ experiments and a simulation algorithm, the research investigated the heat transmission characteristics of the deeply buried pipe energy pile group and optimized different intermittent operation schemes. The findings suggest that prolonged operation of the pile cluster intensifies heat buildup within the pile foundation, thereby adversely affecting the system’s overall heat exchange efficiency. Employing an intermittent operating mode can alleviate this heat accumulation phenomenon, thereby promoting sustained heat exchange performance of the piles over time. To evaluate the comprehensive thermal interaction and energy efficiency ratio of the energy pile heat exchange system, various intermittent operation strategies were compared in the study. Among them, the intermittent operational scheme with a ratio of n = 5 was found to be optimal, with the total average heat transfer rate of the pile set only 0.51% lower than that of the continuous operational mode, but the overall energy efficiency ratio improved by 19.6%. The intermittent operational mode proposed in this study can achieve the goal of saving energy and efficiently extracting geothermal resources, providing theoretical guidance for the extraction and utilization of subsurface geothermal power by energy piles.

Fixed‐time event‐dependent intermittent control for reaction‐diffusion systems

AbstractThis article discusses the fixed‐time stabilization (FxTS) problem for reaction‐diffusion systems (RDSs). First, this article designs a fixed‐time event‐dependent intermittent control strategy by introducing four nonlinear functions. The switching of the controller between the working and resting phases is no longer time‐dependent, avoiding the relatively stringent constraint on the control ratio in the existing studies of FxTS based on discontinuous‐time control. Under the presented event‐dependent intermittent control strategy, RDSs can be stabilized within a fixed time and the settling time can be estimated as the zero point of the pre‐defined nonlinear function. In contrast to the existing estimation methods, the estimation method of this article is more universal and less conservative. Moreover, this article derives several generalized stabilization criteria for RDSs under event‐dependent intermittent control employing the Lyapunov method and mathematical induction. Finally, an example is given to clarify the validity of the fixed‐time control strategy and the FxTS criteria.

Cross-correlation adjustment full-waveform inversion with source encoding in ultrasound computed tomography

Full-waveform inversion (FWI) is one of the leading-edge techniques in ultrasound computed tomography (USCT). FWI reconstructs the images of sound speed by iteratively minimizing the difference between the predicted and measured signals. The challenges of FWI are to improve its stability and reduce its computational cost. In this paper, a new USCT algorithm based on cross-correlation adjustment FWI with source encoding (CCAFWI-SE) is proposed. In this algorithm, the gradient is adjusted using the intermediate signals as the inversion target rather than the measured signals during iteration. The intermediate signals are generated using the travel time difference calculated by cross-correlation. In the case of conventional FWI failure, using the proposed algorithm, the estimated sound speed can converge toward the ground truth. To reduce the computational cost, an intermittent update strategy is implemented. This strategy only requires one time for the calculation of the travel time difference per stage, so that the source encoding can be used. Simulation and laboratory experiments are implemented to validate this approach. The experiment results show it has successfully recovered the sound speed model, while conventional FWI failed when the initial model greatly differed from the ground truth. This verifies that our approach improves the stability of the reconstruction in USCT. In practice, additional computational costs can be reduced by combining our approach with existing methods. The proposed approach increases the robustness of the FWI and expands its application.

Martensitic transformation induced strength-ductility synergy in additively manufactured maraging 250 steel by thermal history engineering

Maraging steels are known for their exceptional strength but suffer from limited work hardening and ductility. Here, we report an intermittent printing strategy to tailor the microstructure and mechanical properties of maraging 250 steel via tuning the thermal history during wire-arc directed energy deposition. By introducing a dwell time between adjacent layers, the maraging 250 steel is cooled below the martensite start temperature, triggering thermally-driven martensitic transformation during the printing process. Thermal cycling during subsequent layer deposition results in the formation of reverted austenite which shows a refined microstructure and induces elemental segregation between martensite and reverted austenite. The Ni enrichment in the austenite promotes stabilization of the reverted austenite upon cooling to room temperature. The reverted austenite is metastable during deformation, leading to strain-induced martensitic transformation under loading. Specifically, a 3 min interlayer dwell time produces a maraging 250 steel with approximately 8% reverted austenite, resulting in improved work hardening via martensitic transformation induced plasticity during deformation. Meanwhile, the higher cooling rate and refined prior austenite grains lead to substantially refined martensitic grains (by approximately fivefold) together with an increased dislocation density. With 3 min interlayer dwell time, the yield strength of the printed maraging 250 steel increases from 836 MPa to 990 MPa, and the uniform elongation is doubled from 3.2% to 6.5%. This intermittent deposition strategy demonstrates the potential to tune the microstructure of maraging steels for achieving strength-ductility synergy by engineering the thermal history during additive manufacturing.

Revealing the impacts of intermittent aeration on nitrogen and phosphorus removal in powder carrier system from interfacial thermodynamics and metagenomic analysis

Intermittent aeration strategy has attracted significant attention due to its benefits of low oxygen and carbon source consumption. However, the feasibility of intermittent aeration in the powder carrier process and its effect on micro-granule formation remain unclear. This study investigated the impacts of intermittent aeration on the powder carrier system through interfacial thermodynamics and metagenomic analysis. The results demonstrated that total nitrogen removal efficiency increased from 61.1 ± 2.6 % to 89.7 ± 3.7 % under intermittent aeration, while the PO43-–P removal efficiency increased from 47.6 ± 4.7 % to 81.6 ± 3.9 %. The interfacial free energy of micro-granules was reduced from –4.85 mJ/m2 to –16.03 mJ/m2 due to aeration mode, resulting in a larger micro-granule size (185.24 ± 15.25 μm) and enhanced aggregation ability. Significant enhancements in tryptophan-like substances and hydrophobic functional groups (β-sheet, protonated amines, and C-(C/H)) in EPS under intermittent aeration likely contributed to the increased hydrophobicity and reduced interfacial free energy. The abundances of norank_NS9_marine_group (4.17 %), norank_Comamonadaceae (4.57 %), and Terrimonas (3.44 %) were increased, further driving the synergy of nitrogen removal of simultaneous partial nitrification and denitrification and endogenous denitrification. Correlation analysis confirmed that intermittent aeration primarily affected gene expression involved in the partial nitrification process, and that denitrification genes were enriched by increased hydrophobic components and micro-granule size. These results provide deeper insights into the key influencing factors and mechanisms of the powder carrier system, and offer a theoretical basis for process optimization.

Secure intermittent impulsive consensus control for fractional-order multiagent systems under denial-of-service and deception attacks

This article addresses the secure consensus problem of fractional-order multiagent systems (FOMASs) under denial-of-service (DoS) and deception attacks in the intermittent impulsive control framework. Unlike previous cyber attack models, the multiple attacks are considered, which the agent-to-agent communication channels and the controller-to-actuator channels are randomly subjected to deception and DoS attacks, respectively. Some random variables that follow the Bernoulli distribution are proposed, which are related to the communication channels between adjacent agents to describe deceptive attack behavior. To reduce control costs and resist cyber attacks, a novel intermittent impulsive control strategy is designed to make the FOMASs achieve consensus faster, when DoS attacks are sleeping. The designed intermittent impulsive control includes the advantages of discrete sampling control and intermittent control, which means that it can reduce the injection of erroneous data by constraining the frequency of information transmission. Furthermore, some sufficient criteria including the parameters of multiple attacks are yielded to ensure mean-square quasi-consensus of FOMASs. Finally, two examples are provided to validate the rationality for the presented security control method in this study from the perspective of numerical simulation experiments.

A phase I/Ib study of the aurora kinase A inhibitor alisertib in combination with osimertinib in advanced osimertinib-resistant EGFR-mutated lung cancer.

8572 Background: The third-generation Epidermal Growth Factor Receptor (EGFR) tyrosine kinase inhibitor (TKI) osimertinib is effective for the treatment of advanced EGFR-mutated lung adenocarcinoma (LUAD), however treatment resistance invariably occurs. We previously identified Aurora Kinase A (AURKA) activation as a mechanism of resistance to osimertinib. Alisertib is an oral, selective, small-molecule inhibitor of AURKA. We evaluated the combination of alisertib with osimertinib in a phase I/Ib study of patients with advanced EGFR-mutated LUAD who experienced disease progression on prior treatment with osimertinib monotherapy. Methods: 21 total patients were treated in an open-label, single-center phase I trial (NCT04085315). 10 patients were treated in a 3+3 dose escalation phase with alisertib using an intermittent dosing strategy of 30 mg (n = 6) or 40 mg (n = 4) twice daily (BID) on days (d) 1-3, 8-11, and 15-17 of a 28-day cycle in combination with osimertinib 80 mg daily. 11 additional patients were treated at the 30 mg alisertib intermittent dosing schedule in combination with osimertinib 80 mg daily in a Phase Ib dose expansion. Primary endpoints were safety, maximum tolerated dose (MTD), and recommended phase II dose (RP2D) of the alisertib and osimertinib combination. Secondary endpoints were investigator-assessed objective response rate (ORR) by RECIST 1.1 criteria, depth of response (DoR), disease control rate (DCR) for at least 12 weeks, progression-free survival (PFS) and overall survival (OS). Results: 21 patients with stage IV EGFR-mutated LUAD (76.1% exon 19 deletion; 14.3% L858R; 9.5 % L861Q) who had progressed on osimertinib were enrolled. 10 (47.6%) patients had received only first-line osimertinib, while 11 (52.3%) had received ≥ 2 lines of prior therapy. Common treatment-related adverse events were neutropenia (42.9%), anemia (42.9%), and diarrhea (38.1%). 2 patients had dose limiting toxicities from grade 4 neutropenia at the alisertib 40mg BID dose level. 2 patients had serious adverse events related to the study drugs, including grade 3 constipation and grade 4 anemia. There were no treatment-related deaths. Intermittent alisertib 30 mg BID with osimertinib 80 mg daily was the MTD and R2PD. ORR for all enrolled patients was 9.5% (95% CI: 1.2% to 30.4%), DCR was 81% (95% CI: 58.1% to 94.6%), and median DoR was -4 % (95% CI: -15% to 10%). The median PFS was 5.5 months (95% CI: 3.7 – 13.2 months) and median OS was 23.5 months (95% CI: 11.9 months – NR). Conclusions: Intermittent dosing of alisertib 30 mg BID in combination with osimertinib 80 mg daily demonstrated no dose limiting toxicities and was identified as the RP2D. While ORR was < 10%, DCR was > 80% and the median PFS was 5.5 months. These results are comparable to other emerging therapies for patients with advanced osimertinib resistant EGFR-mutated LUAD and warrants further exploration. Clinical trial information: NCT04085315 .

Event-Based Intermittent Formation Control of Multi-UAV Systems Under Deception Attacks.

This article investigates the problem of event-based intermittent formation control for multi-UAV systems subject to deception attacks. Compared to the available research studies on multi-UAV systems with continuous control strategy, the proposed intermittent control strategy saves a large amount of computation resources. An average method is introduced in developing the event-triggered mechanism (ETM) such that the amount of unexpected triggering events induced by uncertain disturbances is greatly reduced. Moreover, such a mechanism can further decrease the average data-releasing rate, thereby alleviating the burden of network bandwidth. Sufficient conditions for multi-UAV systems with deception attacks to achieve the predefined formation are obtained with the aid of Lyapunov stability theory. Finally, the validity of the proposed theoretical results is demonstrated via a simulation example.

Assessing impact of intermittent window opening strategies on pathogen-laden droplet dispersion in a coach bus

Assessing impact of intermittent window opening strategies on pathogen-laden droplet dispersion in a coach bus