Delay effects on the stability of large ecosystems.

The common intuition among the ecologists of the midtwentieth century was that large ecosystems should be more stable than those with a smaller number of species. This view was challenged by Robert May, who found a stability bound for randomly assembled ecosystems; they become unstable for a sufficiently large number of species. In the present work, we show that May's bound greatly changes when the past population densities of a species affect its own current density. This is a common feature in real systems, where the effects of species' interactions may appear after a time lag rather than instantaneously. The local stability of these models with self-interaction is described by bounds, which we characterize in the parameter space. We find a critical delay curve that separates the region of stability from that of instability, and correspondingly, we identify a critical frequency curve that provides the characteristic frequencies of a system at the instability threshold. Finally, we calculate analytically the distributions of eigenvalues that generalize Wigner's as well as Girko's laws. Interestingly, we find that, for sufficiently large delays, the eigenvalues of a randomly coupled system are complex even when the interactions are symmetric.

Brain-heart interaction disruption in major depressive disorder: disturbed rhythm modulation of the cardiac cycle on brain transient theta bursts.

Brain neurons support arousal and cognitive activity in the form of spectral transient bursts and cooperate with the peripheral nervous system to adapt to the surrounding environment. However, the temporal dynamics of brain-heart interactions have not been confirmed, and the mechanism of brain-heart interactions in major depressive disorder (MDD) remains unclear. This study aimed to provide direct evidence for brain-heart synchronization in temporal dynamics and clarify the mechanism of brain-heart interaction disruption in MDD. Eight-minute resting-state (closed eyes) electroencephalograph and electrocardiogram signals were acquired simultaneously. The Jaccard index (JI) was used to measure the temporal synchronization between cortical theta transient bursts and cardiac cycle activity (diastole and systole) in 90 MDD patients and 44 healthy controls (HCs) at rest. The deviation JI was used to reflect the equilibrium of brain activity between diastole and systole. The results showed that the diastole JI was higher than the systole JI in both the HC and MDD groups; compared to HCs, the deviation JI attenuated at F4, F6, FC2, and FC4 in the MDD patients. The eccentric deviation JI was negatively correlated with the despair factor scores of the HAMD, and after 4 weeks of antidepressant treatment, the eccentric deviation JI was positively correlated with the despair factor scores of the HAMD. It was concluded that brain-heart synchronization existed in the theta band in healthy individuals and that disturbed rhythm modulation of the cardiac cycle on brain transient theta bursts at right frontoparietal sites led to brain-heart interaction disruption in MDD.

Global dynamics of a time-delayed nonlocal reaction-diffusion model of within-host viral infections.

In this paper, we study a time-delayed nonlocal reaction-diffusion model of within-host viral infections. We introduce the basic reproduction number R 0 and show that the infection-free steady state is globally asymptotically stable when R 0 ≤ 1 , while the disease is uniformly persistent when R 0 > 1 . In the case where all coefficients and reaction terms are spatially homogeneous, we obtain an explicit formula of R 0 and the global attractivity of the positive constant steady state. Numerically, we illustrate the analytical results, conduct sensitivity analysis, and investigate the impact of drugs on curtailing the spread of the viruses.

Energetics of sinusoidal exercise below and across critical power and the effects of fatigue.

PURPOSE: Previous studies investigating sinusoidal exercise were not devoted to an analysis of its energetics and of the effects of fatigue. We aimed to determine the contribution of aerobic and anaerobic lactic metabolism to the energy balance and investigate the fatigue effects on the cardiorespiratory and metabolic responses to sinusoidal protocols, across and below critical power (CP). METHODS: Eight males (26.6 ± 6.2 years; 75.6 ± 8.7 kg; maximum oxygen uptake 52.8 ± 7.9 ml·min-1·kg-1; CP 218 ± 13 W) underwent exhausting sinusoidal cycloergometric exercises, with sinusoid midpoint (MP) at CP (CPex) and 50 W below CP (CP-50ex). Sinusoid amplitude (AMP) and period were 50 W and 4 min, respectively. MP, AMP, and time-delay (tD) between mechanical and metabolic signals of expiratory ventilation ( V ˙ E ), oxygen uptake ( V ˙ O 2 ), and heart rate ( f H ) were assessed sinusoid-by-sinusoid. Blood lactate ([La-]) and rate of perceived exertion (RPE) were determined at each sinusoid. RESULTS: V ˙ O 2 AMP was 304 ± 11 and 488 ± 36 ml·min-1 in CPex and CP-50ex, respectively. Asymmetries between rising and declining sinusoid phases occurred in CPex (36.1 ± 7.7 vs. 41.4 ± 9.7 s for V ˙ O 2 tD up and tD down, respectively; P < 0.01), with unchanged tDs. V ˙ O 2 MP and RPE increased progressively during CPex. [La-] increased by 2.1 mM in CPex but remained stable during CP-50ex. Anaerobic contribution was larger in CPex than CP-50ex. CONCLUSION: The lower aerobic component during CPex than CP-50ex associated with lactate accumulation explained lower V ˙ O 2 AMP in CPex. The asymmetries in CPex suggest progressive decline of muscle phosphocreatine concentration, leading to fatigue, as witnessed by RPE.

Efficient EPID-based quality assurance of beam time delay for respiratory-gated radiotherapy with validation on Catalyst™ and AlignRT™ systems.

PURPOSE: To propose a straightforward and time-efficient quality assurance (QA) approach of beam time delay for respiratory-gated radiotherapy and validate the proposed method on typical respiratory gating systems, Catalyst™ and AlignRT™. METHODS: The QA apparatus was composed of a motion platform and a Winston-Lutz cube phantom (WL3) embedded with metal balls. The apparatus was first scanned in CT-Sim and two types of QA plans specific for beam on and beam off time delay, respectively, were designed. Static reference images and motion testing images of the WL3 cube were acquired with EPID. By comparing the position differences of the embedded metal balls in the motion and reference images, beam time delays were determined. The proposed approach was validated on three linacs with either Catalyst™ or AlignRT™ respiratory gating systems. To investigate the impact of energy and dose rate on beam time delay, a range of QA plans with Eclipse (V15.7) were devised with varying energy and dose rates. RESULTS: For all energies, the beam on time delays in AlignRT™ V6.3.226, AlignRT™ V7.1.1, and Catalyst™ were 92.13 ± $ \pm $ 5.79 ms, 123.11 ± $ \pm $ 6.44 ms, and 303.44 ± $ \pm $ 4.28 ms, respectively. The beam off time delays in AlignRT™ V6.3.226, AlignRT™ V7.1.1, and Catalyst™ were 121.87 ± $ \pm $ 1.34 ms, 119.33 ± $ \pm $ 0.75 ms, and 97.69 ± $ \pm $ 2.02 ms, respectively. Furthermore, the beam on delays decreased slightly as dose rates increased for all gating systems, whereas the beam off delays remained unaffected. CONCLUSIONS: The validation results demonstrate the proposed QA approach of beam time delay for respiratory-gated radiotherapy was both reproducible and time-efficient to practice for institutions to customize accordingly.

A Reduced Complexity Acoustic-Based 3D DoA Estimation with Zero Cyclic Sum.

Accurate direction of arrival (DoA) estimation is paramount in various fields, from surveillance and security to spatial audio processing. This work introduces an innovative approach that refines the DoA estimation process and demonstrates its applicability in diverse and critical domains. We propose a two-stage method that capitalizes on the often-overlooked secondary peaks of the cross-correlation function by introducing a reduced complexity DoA estimation method. In the first stage, a low complexity cost function based on the zero cyclic sum (ZCS) condition is used to allow for an exhaustive search of all combinations of time delays between pairs of microphones, including primary peak and secondary peaks of each cross-correlation. For the second stage, only a subset of the time delay combinations with the lowest ZCS cost function need to be tested using a least-squares (LS) solution, which requires more computational effort. To showcase the versatility and effectiveness of our method, we apply it to the challenging acoustic-based drone DoA estimation scenario using an array of four microphones. Through rigorous experimentation with simulated and actual data, our research underscores the potential of our proposed DoA estimation method as an alternative for handling complex acoustic scenarios. The ZCS method demonstrates an accuracy of 89.4%±2.7%, whereas the ZCS with the LS method exhibits a notably higher accuracy of 94.0%±3.1%, showcasing the superior performance of the latter.

Multi-Parameter Characterization of Liquid-to-Ice Phase Transition Using Bulk Acoustic Waves.

The detection of the liquid-to-ice transition is an important challenge for many applications. In this paper, a method for multi-parameter characterization of the liquid-to-ice phase transition is proposed and tested. The method is based on the fundamental properties of bulk acoustic waves (BAWs). BAWs with shear vertical (SV) or shear horizontal (SH) polarization cannot propagate in liquids, only in solids such as ice. BAWs with longitudinal (L) polarization, however, can propagate in both liquids and solids, but with different velocities and attenuations. Velocities and attenuations for L-BAWs and SV-BAWs are measured in ice using parameters such as time delay and wave amplitude at a frequency range of 1-37 MHz. Based on these measurements, relevant parameters for Rayleigh surface acoustic waves and Poisson's modulus for ice are determined. The homogeneity of the ice sample is also detected along its length. A dual sensor has been developed and tested to analyze two-phase transitions in two liquids simultaneously. Distilled water and a 0.9% solution of NaCl in water were used as examples.

Distributed State Observer for Systems with Multiple Sensors under Time-Delay Information Exchange.

The issues of state estimations based on distributed observers for linear time-invariant (LTI) systems with multiple sensors are discussed in this paper. We deal with the scenario when the information exchange has known time delays, and aim at designing a distributed observer for each subsystem such that each distributed observer can estimate the system state asymptotically by rejecting the time delay. To begin with, by rewriting the target system in a connecting form, a subsystem which is affected by the time-delay states of other nodes is established. And then, for this subsystem, a distributed observer with time delay is constructed. Moreover, an equivalent state transformation is made for the observer error dynamic system based on the observable canonic decomposition theorem. Further, in order to ensure that the distributed observer error dynamic system is asymptotically stable even if there exists a time delay, a linear matrix inequality (LMI) which is relative to the Laplace matrix is elaborately set up, and a special Lyapunov function candidate based on the LMI is considered. Next, based on the Lyapunov function and Lyapunov stability theory, we prove that the error dynamic system of the distributed observer is asymptotically stable, and the observer gain is determined by a feasible solution of the LMI. Finally, a simulation example is given to illustrate the effectiveness of the proposed method.

Time Delay Study of Ultrasonic Gas Flowmeters Based on VMD-Hilbert Spectrum and Cross-Correlation.

The accuracy of ultrasonic flowmeter time delay measurement is directly affected by the processing method of the ultrasonic echo signal. This paper proposes a method for estimating the time delay of the ultrasonic gas flowmeter based on the Variational Mode Decomposition (VMD)-Hilbert Spectrum and Cross-Correlation (CC). The method improves the accuracy of the ultrasonic gas flowmeter by enhancing the quality of the echo signal. To denoise forward and reverse ultrasonic echo signals collected at various wind speeds, a Butterworth filter is initially used. The ultrasonic echo signals are then analyzed by Empirical Mode De-composition (EMD) and VMD analysis to obtain the Intrinsic Mode Function (IMF) containing distinct center frequencies, respectively. The Hilbert spectrum time-frequency diagram is used to evaluate the results of the VMD and EMD decompositions. It is found that the IMF decomposed by VMD has a better filtering performance and better anti-interference performance. Therefore, the IMF with a better effect is selected for signal reconstruction. The ultrasonic time delay is then calculated using the Cross-Correlation algorithm. The self-developed ultrasonic gas flowmeter was tested on the experimental platform of the gas flow standard devices using this signal processing method. The results show a maximum indication error of 0.84% within the flow range of 60-606 m3/h, with a repeatability of no more than 0.29%. These results meet the 1-level accuracy requirements as outlined in the national ultrasonic flowmeters calibration regulation JJG1030-2007.

Balancing the Efficiency and Sensitivity of Defect Inspection of Non-Patterned Wafers with TDI-Based Dark-Field Scattering Microscopy.

In semiconductor manufacturing, defect inspection in non-patterned wafer production lines is essential to ensure high-quality integrated circuits. However, in actual production lines, achieving both high efficiency and high sensitivity at the same time is a significant challenge due to their mutual constraints. To achieve a reasonable trade-off between detection efficiency and sensitivity, this paper integrates the time delay integration (TDI) technology into dark-field microscopy. The TDI image sensor is utilized instead of a photomultiplier tube to realize multi-point simultaneous scanning. Experiments illustrate that the increase in the number of TDI stages and reduction in the column fixed pattern noise effectively improve the signal-to-noise ratio of particle defects without sacrificing the detecting efficiency.

Guided Lamb Wave Array Time-Delay-Based MUSIC Algorithm for Impact Imaging.

Composite materials, valued in aerospace for their stiffness, strength and lightness, require impact monitoring for structural health, especially against low-velocity impacts. The MUSIC algorithm, known for efficient directional scanning and easy sensor deployment, is gaining prominence in this area. However, in practical engineering applications, the broadband characteristics of impact response signals and the time delay errors in array elements' signal reception lead to inconsistencies between the steering vector and the actual signal subspace, affecting the precision of the MUSIC impact localization method. Furthermore, the anisotropy of composite materials results in time delay differences between array elements in different directions. If the MUSIC algorithm uses a fixed velocity value, this also introduces time delay errors, further reducing the accuracy of localization. Addressing these challenges, this paper proposes an innovative MUSIC algorithm for impact imaging using a guided Lamb wave array, with an emphasis on time delay management. This approach focuses on the extraction of high-energy, single-frequency components from impact response signals, ensuring accurate time delay measurement across array elements and enhancing noise resistance. It also calculates the average velocity of single-frequency components in varying directions for an initial impact angle estimation. This estimated angle then guides the selection of a specific single-frequency velocity, culminating in precise impact position localization. The experimental evaluation, employing equidistantly spaced array elements to capture impact response signals, assessed the effectiveness of the proposed method in accurately determining array time delays. Furthermore, impact localization tests on reinforced composite structures were conducted, with the results indicating high precision in pinpointing impact locations.

Adaptive Fuzzy Integral Sliding Mode Cooperative Control Based on Time-Delay Estimation for Free-Floating Close-Chain Manipulators.

Space manipulators are expected to perform more challenging missions in on-orbit service (OOS) systems, but there are some unique characteristics that are not found on ground-based robots, such as dynamic coupling between space bases and manipulators, limited fuel supply, and working with unfixed bases. This paper focuses on trajectory-tracking control and internal force control for free-floating close-chain manipulators. First, the kinematics and dynamics of free-floating close-chain manipulators are given using the momentum conservation and spatial operator algebra (SOA) methodologies, respectively. Furthermore, an adaptive fuzzy integral sliding mode controller (AFISMC) based on time delay estimation (TDE) was designed for trajectory-tracking control, and a proportional-integral (PI) control strategy was adopted for internal force control. The global asymptotic stability of the proposed controller was proven by using the Lyapunov methodology. Three cases were conducted to verify the efficiency of the controller by using numerical simulations on two six-link manipulators with a free-floating base. The controller presents the desired tracking capability.

Research on Delamination Damage Quantification Detection of CFRP Bending Plate Based on Lamb Wave Mode Control.

The carbon-fiber-reinforced polymer (CFRP) bending structure is widely used in aviation. The emergence and spread of delamination damage will decrease the safety of in-service bending structures. Lamb waves can effectively identify delamination damage as a high-damage-sensitivity detection tool. For this present study, the signal difference coefficient (SDC) was introduced to quantify delamination damage and evaluate the sensitivity of A0-mode and S0-mode Lamb waves to delamination damage. The simulation results show that compared with the S0-mode Lamb wave, the A0-mode Lamb wave exhibits higher delamination damage sensitivity. The delamination damage can be quantified based on the strong correlation between the SDC and the delamination damage size. The control effect of the linear array PZT phase time-delay method on the Lamb wave mode was investigated by simulation. The phase time-delay method realizes the generation of a single-mode Lamb wave, which can separately excite the A0-mode and S0-mode Lamb wave to identify delamination damage of different sizes. The A0-mode Lamb wave was excited by the developed one-dimensional miniaturized linear comb transducer (LCT), which was used to conduct the detection experiment on the CFRP bending plate with delamination damage sizes of Φ6.0 mm, Φ10.0 mm, and Φ15.0 mm. The experimental results verify the correctness of the simulation. According to the Hermite interpolation results of the finite-element simulation data, the relationship between the delamination damage size and the SDC was fitted by the Gaussian function and Rational function, which can accurately quantify the delamination damage. The absolute error of the delamination damage quantification with Gaussian and Rational fitting expression does not exceed 0.8 mm and 0.7 mm, and the percentage error is not more than 8% and 7%. The detection and signal processing methods employed in the present research are easy to operate and implement, and accurate delamination damage quantification results have been obtained.

Accurate and Efficient Simulation of Very High-Dimensional Neural Mass Models with Distributed-Delay Connectome Tensors.

This paper introduces methods and a novel toolbox that efficiently integrates high-dimensional Neural Mass Models (NMMs) specified by two essential components. The first is the set of nonlinear Random Differential Equations (RDEs) of the dynamics of each neural mass. The second is the highly sparse three-dimensional Connectome Tensor (CT) that encodes the strength of the connections and the delays of information transfer along the axons of each connection. To date, simplistic assumptions prevail about delays in the CT, often assumed to be Dirac-delta functions. In reality, delays are distributed due to heterogeneous conduction velocities of the axons connecting neural masses. These distributed-delay CTs are challenging to model. Our approach implements these models by leveraging several innovations. Semi-analytical integration of RDEs is done with the Local Linearization (LL) scheme for each neural mass, ensuring dynamical fidelity to the original continuous-time nonlinear dynamic. This semi-analytic LL integration is highly computationally-efficient. In addition, a tensor representation of the CT facilitates parallel computation. It also seamlessly allows modeling distributed delays CT with any level of complexity or realism. This ease of implementation includes models with distributed-delay CTs. Consequently, our algorithm scales linearly with the number of neural masses and the number of equations they are represented with, contrasting with more traditional methods that scale quadratically at best. To illustrate the toolbox's usefulness, we simulate a single Zetterberg-Jansen and Rit (ZJR) cortical column, a single thalmo-cortical unit, and a toy example comprising 1000 interconnected ZJR columns. These simulations demonstrate the consequences of modifying the CT, especially by introducing distributed delays. The examples illustrate the complexity of explaining EEG oscillations, e.g., split alpha peaks, since they only appear for distinct neural masses. We provide an open-source Script for the toolbox.

Structural basis of envelope and phase intrinsic coupling modes in the cerebral cortex.

Intrinsic coupling modes (ICMs) can be observed in ongoing brain activity at multiple spatial and temporal scales. Two families of ICMs can be distinguished: phase and envelope ICMs. The principles that shape these ICMs remain partly elusive, in particular their relation to the underlying brain structure. Here we explored structure-function relationships in the ferret brain between ICMs quantified from ongoing brain activity recorded with chronically implanted micro-ECoG arrays and structural connectivity (SC) obtained from high-resolution diffusion MRI tractography. Large-scale computational models were used to explore the ability to predict both types of ICMs. Importantly, all investigations were conducted with ICM measures that are sensitive or insensitive to volume conduction effects. The results show that both types of ICMs are significantly related to SC, except for phase ICMs when using measures removing zero-lag coupling. The correlation between SC and ICMs increases with increasing frequency which is accompanied by reduced delays. Computational models produced results that were highly dependent on the specific parameter settings. The most consistent predictions were derived from measures solely based on SC. Overall, the results demonstrate that patterns of cortical functional coupling as reflected in both phase and envelope ICMs are both related, albeit to different degrees, to the underlying structural connectivity in the cerebral cortex.

On-scene time delays for epileptic seizures in emergencies during a social pandemic: A population-based study.

OBJECTIVES: The on-scene time of Emergency Medical Services (EMS), including time for hospital selection, is critical for people in an emergency. However, the outbreak of the novel coronavirus disease 2019 (COVID-19) led to longer delays in providing immediate care for individuals with non-COVID-19-related emergencies, such as epileptic seizures. This study aimed to examine factors associated with on-scene time delays for people with epilepsy (PWE) with seizures needing immediate amelioration. MATERIALS & METHODS: We conducted a population-based retrospective cohort study for PWE transported by EMS between 2016 and 2021. We used data from the Hiroshima City Fire Service Bureau database, divided into three study periods: "Pre period", the period before the COVID pandemic (2016-2019); "Early period", the early period of the COVID pandemic (2020); and "Middle period", the middle period of the COVID pandemic (2021). We performed linear regression modeling to identify factors associated with changes in EMS on-scene time for PWE during each period. In addition, we estimated the rate of total EMS call volume required to maintain the same on-scene time for PWE transported by EMS during the pandemic expansion. RESULTS: Among 2,205 PWE transported by EMS, significant differences in mean age and prevalence of impaired consciousness were found between pandemic periods. Total EMS call volume per month for all causes during the same month <5,000 (-0.55 min, 95% confidence interval [CI] -1.02 - -0.08, p = 0.022) and transport during the Early period (-1.88 min, 95%CI -2.75 - -1.00, p < 0.001) decreased on-scene time, whereas transport during the Middle period (1.58 min, 95%CI 0.70 - 2.46, p < 0.001) increased on-scene time for PWE transported by EMS. The rate of total EMS call volume was estimated as 0.81 (95%CI -0.04 - 1.07) during the expansion phase of the pandemic to maintain the same degree of on-scene time for PWE transported by EMS before the pandemic. CONCLUSIONS: On-scene time delays on PWE in critical care settings were observed during the Middle period. When the pandemic expanded, the EMS system required resource allocation to maintain EMS for time-sensitive illnesses such as epileptic seizures. Timely system changes are critical to meet dramatic social changes.

A Nonlinear Delay Model for Metabolic Oscillations in Yeast Cells.

We introduce two time-delay models of metabolic oscillations in yeast cells. Our model tests a hypothesis that the oscillations occur as multiple pathways share a limited resource which we equate to the number of available ribosomes. We initially explore a single-protein model with a constraint equation governing the total resource available to the cell. The model is then extended to include three proteins that share a resource pool. Three approaches are considered at constant delay to numerically detect oscillations. First, we use a spectral element method to approximate the system as a discrete map and evaluate the stability of the linearized system about its equilibria by examining its eigenvalues. For the second method, we plot amplitudes of the simulation trajectories in 2D projections of the parameter space. We use a history function that is consistent with published experimental results to obtain metabolic oscillations. Finally, the spectral element method is used to convert the system to a boundary value problem whose solutions correspond to approximate periodic solutions of the system. Our results show that certain combinations of total resource available and the time delay, lead to oscillations. We observe that an oscillation region in the parameter space is between regions admitting steady states that correspond to zero and constant production. Similar behavior is found with the three-protein model where all proteins require the same production time. However, a shift in the protein production rates peaks occurs for low available resource suggesting that our model captures the shared resource pool dynamics.

Global stability of latency-age/stage-structured epidemic models with differential infectivity.

In this paper, we first formulate a system of ODEs-PDE to model diseases with latency-age and differential infectivity. Then, based on the ways how latent individuals leave the latent stage, one ODE and two DDE models are derived. We only focus on the global stability of the models. All the models have some similarities in the existence of equilibria. Each model has a threshold dynamics for global stability, which is completely characterized by the basic reproduction number. The approach is the Lyapunov direct method. We propose an idea on constructing Lyapunov functionals for the two DDE and the original ODEs-PDE models. During verifying the negative (semi-)definiteness of derivatives of the Lyapunov functionals along solutions, a novel positive definite function and a new inequality are used. The idea here is also helpful in applying the Lyapunov direct method to prove the global stability of some epidemic models with age structure or delays.

Dynamical analysis of a glucose-insulin regulatory system with insulin-degrading enzyme and multiple delays.

This paper investigates the dynamics of a glucose-insulin regulatory system model that incorporates: (1) insulin-degrading enzyme in the insulin equation; and (2) discrete time delays respectively in the insulin production term, hepatic glucose production term, and the insulin-degrading enzyme. We provide rigorous results of our model including the asymptotic stability of the equilibrium solution and the existence of Hopf bifurcation. We show that analytically and numerically at a certain value the time delays driven stability or instability occurs when the corresponding model has an interior equilibrium. Moreover, we illustrate the oscillatory regulation and insulin secretion via numerical simulations, which show that the model dynamics exhibit physiological observations and more information by allowing parameters to vary. Our results may provide useful biological insights into diabetes for the glucose-insulin regulatory system model.

Cost-effectiveness of improvement strategies for reperfusion treatments in acute ischemic stroke: a systematic review.

BACKGROUND: Reducing delays along the acute stroke pathway significantly improves clinical outcomes for acute ischemic stroke patients eligible for reperfusion treatments. The economic impact of different strategies reducing onset to treatment (OTT) is crucial information for stakeholders in acute stroke management. This systematic review aimed to provide an overview on the cost-effectiveness of several strategies to reduce OTT. METHODS: A comprehensive literature search was conducted in EMBASE, PubMed, and Web of Science until January 2022. Studies were included if they reported 1/ stroke patients treated with intravenous thrombolysis and/or endovascular thrombectomy, 2/ full economic evaluation, and 3/ strategies to reduce OTT. The Consolidated Health Economic Evaluation Reporting Standards statement was applied to assess the reporting quality. RESULTS: Twenty studies met the inclusion criteria, of which thirteen were based on cost-utility analysis with the incremental cost-effectiveness ratio per quality-adjusted life year gained as the primary outcome. Studies were performed in twelve countries focusing on four main strategies: educational interventions, organizational models, healthcare delivery infrastructure, and workflow improvements. Sixteen studies showed that the strategies concerning educational interventions, telemedicine between hospitals, mobile stroke units, and workflow improvements, were cost-effective in different settings. The healthcare perspective was predominantly used, and the most common types of models were decision trees, Markov models and simulation models. Overall, fourteen studies were rated as having high reporting quality (79%-94%). CONCLUSIONS: A wide range of strategies aimed at reducing OTT is cost-effective in acute stroke care treatment. Existing pathways and local characteristics need to be taken along in assessing proposed improvements.