Nitrous oxide emissions and emission factors in hairy vetch-maize sequences: The role of vetch termination timing on nitrogen synchronization

Evaluate the efficacy and safety of a novel partial rebreathing device for early treatment of acute attacks of migraine with aura. Earlier clinical studies have indicated a potential for CO2-enriched gas to be effective for acute treatment of migraine with aura, especially when applied during the early part of the aura stage. We developed a partial rebreathing device inducing moderate, steady-state hypercapnia with normoxia in order to provide a carbon dioxide delivery system combining efficacy, usability, safety, and affordability. This randomized, double-blind, sham-controlled, parallel-group, group-sequential study was conducted at 15 study sites, nine located in the United States and six in Germany, between March 2023 and February 2025. The study enrolled patients aged 18-65 years with migraine with aura. The study had a sequential two-stage study design. At the beginning of stage 1, participants were randomized to active or sham and treated up to four attacks. Participants were instructed to treat from the onset of aura and until 5 min after aura cessation. After having reported four attacks in stage 1, participants had the option to continue into stage 2, an open-label extension in which they could treat up to five attacks with the active device. During stage 1, participants recorded symptom scores in a study diary app at the onset of aura and after 1, 2, 24, and 48 h. The study was terminated at the interim analysis point due to the lack of effect, at which point 142 participants had been enrolled (mean age 39.2 years, 81% women [115/142]). Sixty-seven participants had reported at least one study attack by the time of the study termination. None of the primary or secondary endpoints reached statistical significance. The primary endpoint Absence of Moderate or Severe Pain at 2 hours was 69.7% (46/66) [95.2% confidence interval (CI), 48.5, 90.9] in the sham group and 60.0% (42/70) [95.2% CI, 37.6, 82.4] in the active group (p = 0.379), whereas Pain Freedom at 2 hours was 18.2% (12/66) [95.2% CI, 1.3, 35.1] in the sham group and 21.4% (15/70) [95.2% CI, 3.6, 39.2] in the active group (p = 0.717). Partial rebreathing inducing moderate hypercapnia with normoxia was not effective for aura-stage treatment of migraine-with-aura attacks. The study was preregistered at ClinicalTrials.gov (registration number NCT05546385).

In this paper, we research optimal control problems with incomplete statistical information of parameters. Focusing on a nonlinear switched continuous-time dynamical (NSCTD) system with an uncertain system parameter to characterize the bioconversion of 1,3-propanediol (1,3-PD), we model it as a stochastic variable with known first-moment distribution. Our aim is to develop a distributionally robust optimal control (DROC) strategy to maximize 1,3-PD concentration at the terminal time, considering initial concentrations as control inputs. Solving the DROC problem is tough due to the nonlinear relation between the objective function and the uncertain system parameter. We solve this by deriving an exact Koopman representation to linearize state transitions, converting the NSCTD system into a linear parameter-varying (LPV) system. Then, using duality principles and smoothing techniques, we turn the DROC problem into a single-level optimal control (SLOC) problem. We design a gradient-based algorithm as well as validate its effectiveness and the NSCTD system's modelling ability through simulations.

Relevance. The increase in the number of terminals and the intensity of connections in satellite communication networks with the «star» topology actualizes the problem of choosing an effective mechanism for accessing a common radio channel. The well-known approaches of deterministic and random access have significant limitations. At the same time, there are no clear analytical criteria for choosing between mechanisms depending on the load, which makes it difficult to optimize network performance. Purpose (research): The aim is to compare the effectiveness of two mechanisms for entering satellite terminals into a network with the "star" topology: with specific slot access and with random access. The assessment is aimed at identifying conditions under which one of the mechanisms is superior to the other in key performance indicators. Methods. The solution of the problem is based on a combination of analytical and simulation modeling. To evaluate the effectiveness of random access, a strict combinatorial derivation of the mathematical expectation formula for the number of slots selected by exactly one terminal was carried out. The verification of the analytical model was performed using stochastic modeling in Python. Result. A validated analytical model has been obtained that makes it possible to accurately predict the effectiveness of the random access mechanism. The data obtained is applicable in the design of satellite communication networks to optimize terminal entry time and channel resource allocation. The novelty elements are rigorous analytical inference and verification of the formula for the mathematical expectation of the number of successfully occupied slots with random access, which allows you to accurately predict performance without large-scale modeling. The novelty also includes the establishment of a quantitative criterion for choosing an access mechanism. The proposed model takes into account the real conditions of terminal competition for channel resources and is applicable to the analysis of protocols such as ALOHA and TDMA. Practical significance. The presented solution is proposed to be used in the design and adaptive management of the MAC layer in VSAT satellite networks, IoT systems and telemetry networks. The obtained criteria for selecting an access mechanism can be implemented as dynamic reconfiguration algorithms in software-configurable networks, allowing automatic switching between modes depending on the current load. This will ensure optimal use of bandwidth, minimize delays, and increase overall network stability.

Background: Tissue-nonspecific alkaline phosphatase (TNAP) has emerged as a key contributor to vascular calcification. Prior studies have linked elevated plasma TNAP levels to increased coronary artery calcium scores. Our group demonstrated that TNAP overexpression in endothelial cells promotes calcification and accelerates coronary atherosclerosis. In the current study, we hypothesize that plasma TNAP can directly contribute to vascular calcification. We generated a transgenic mouse model with hepatocyte-targeted TNAP overexpression (hTNAPOE) on a low-density lipoprotein receptor mutant background. Methods: hTNAPOE male and female mice and littermate controls (n=10-12 per group) were fed a western diet to induce atherosclerosis. Cardiac function parameters, along with ascending aortic velocity, were assessed using electrocardiograms. At the terminal time point (42 weeks), the mice were fasted for 5 hours, and plasma was collected by cardiac puncture. Livers and hearts were dissected for histological evaluation. ALP activity was assessed in liver sections to confirm hTNAP overexpression. Plasma alkaline phosphatase (ALP), cholesterol, and triglycerides were measured. Micro-computed tomography (μCT) was employed to detect vascular calcification. Data were analyzed using a two-way ANOVA, accounting for sex and genotype. Results: Our results demonstrated a 10-fold increase in circulating ALP in the plasma of hTNAPOE female mice and a 100-fold increase in male mice compared to control mice (p<0.0001). There was no significant difference in triglycerides; cholesterol levels were mildly elevated in hTNAPOE mice (36% in males and 14% in females, p<0.05). hTNAPOE mice exhibited significantly greater calcification in whole-heart preparations, confirming our hypothesis (p<0.01). Surprisingly, we didn’t see increased aortic root calcification in hTNAPOE mice; however, coronary artery calcification was significantly increased (p<0.05). hTNAPOE mice presented with increased left ventricular mass normalized to body weight, implying the pathophysiologic significance of calcification. While hTNAPOE mice showed higher calcification, ascending aortic velocity, an indicator of stenosis, did not differ between the groups. Conclusion: Overexpression of hTNAP in mice resulted in a significant increase in circulating ALP in plasma and increased coronary calcification.

Optimal test termination time in reliability growth management for systems with multiple failure modes

Abstract In this work, we investigate a numerical procedure for recovering a space-dependent diffusion coefficient in a (sub)diffusion model from the given terminal data, and provide a rigorous numerical analysis of the procedure. By exploiting decay behavior of the observation in time, we establish a novel Hölder type stability estimate for a large terminal time T. This is achieved by novel decay estimates of the (fractional) time derivative of the solution. To numerically recover the diffusion coefficient, we employ the standard output least-squares formulation with an $$H^1(\varOmega )$$ H 1 ( Ω ) -seminorm penalty, and discretize the regularized problem by the Galerkin finite element method with continuous piecewise linear finite elements in space and backward Euler convolution quadrature in time. Further, we provide an error analysis of discrete approximations, and prove a convergence rate that matches the stability estimate. The derived $$L^2(\varOmega )$$ L 2 ( Ω ) error bound depends explicitly on the noise level, regularization parameter and discretization parameters, which gives a useful guideline of the a priori choice of discretization parameters with respect to the noise level in practical implementation. The error analysis is achieved using the conditional stability argument and discrete maximum-norm resolvent estimates. Several numerical experiments are also given to illustrate and complement the theoretical analysis.

Design and application of MDSSP using the MLL3 distribution for pandemic mortality data

A lightweight digital twin model for a single 6G cell operating in the D-band (140 GHz) with a 1 GHz bandwidth is presented in this work with the goal of assessing the cell's capacity, coverage, and terminal time in order to support extended reality (XR) applications. With a tangent dispersion of 3 dB and a path exponent of n = 2.2, the model is based on the free-space loss equation as per ITU-R Recommendation P.525. The instantaneous capacity is determined using the Shannon-Hartley theorem. Three XR sessions are created every minute using a Poisson method, and their durations are determined by an exponential distribution (mean of 120 seconds). In accordance with 3GPP and Ericsson guidelines for normal XR loads, the bit needs per user are randomly selected to fall between 40 and 120 Mb/s. The average coverage was around 92%, the average cell capacity was approximately 5.1 Gb/s, and the edge capacity (lowest quintile) was approximately 230 Mb/s, according to fifty statistical forecasts. Additionally, the 95th percentile round-trip latency was 3.9 ms, which is significantly less than the permitted maximum (10–20 ms) for immersive XR research. These findings suggest that modest XR loads may be supported by a 250-meter cell with a high-gain antenna layout without the need to immediately lower the radius or raise the transmitted power. However, the model remains theoretical and simplified, excluding geometric blockage and cell overlap in complex metropolitan environments.

Abstract BACKGROUND Glioblastomas (GBM) are constructs that demonstrate a high degree of adaptability, capable of altering their characteristics to suit the prevailing conditions and thereby ensure their own survival. Recent studies have demonstrated that tumors not just undergo morphological changes over time, but their metabolic processes also exhibit variability depending on their status. In this study we assessed dynamics of the metabolome in the tumor microenvironment (TME) by collecting interstitial fluid (ISF), with Open Flow Microperfusion (cOFM), cerebrospinal fluid (CSF), and blood from human GBM-bearing animals at several time points along the tumor progression timeline. The samples were then compared to those collected from non-GBM-bearing animals (non-GBM controls) in order to enhance the focus on the metabolome in TME and to identify new potential metabolic biomarkers or biomarker profiles that reflect the local situation of TME. MATERIAL AND METHODS We applied the atraumatic access to human GBM xenograft with cOFM that allows sampling of metabolites inside the TME with functional blood-brain barrier using U87 cells. Cancer cells were implanted orthotopically into the striatum region of immunodeficient mouse model (Athymic nude) by using the previously implanted cOFM. Tumor growth was monitored with magnetic-resonance-imaging. On days 7, 10, and 15 post-implantation, ISF from TME was collected with cOFM. CSF and brain tissue were collected from the same animals at terminal time point. Blood plasma samples were taken at matching time points. The collected samples were analyzed using a LC-HRMS metabolomics platform. Metabolomics data from GBM-bearing animals were analyzed and compared with that from non-GBM controls. RESULTS Tumor progression curve indicated a typical development of a U87 tumor. Moreover, histology revealed that even multiple collections from TME did not affect the tumor morphology. The metabolome from the GBM-bearing animals showed distinct metabolic patterns when compared to that from the non-GBM controls. Furthermore, the metabolome within the GBM group demonstrated distinguishing patterns at the different collection time points along the tumor progression trajectory. This metabolic adaption was visible in particularly in energy metabolism and inflammatory pathway. CONCLUSION This in vivo xenograft study not just demonstrated the unique capabilities of the cOFM technology investigating evolution of brain tumors, but also nicely showed the ability of GBM tumors adapting their metabolism with respect to their current needs during tumor progression. These results indicate potential therapeutic windows and highlight the importance of the time point for the GBM treatment.

Long-term dynamics of the spinal cord injury neuroinflammatory response and sensory dysfunction in female mice.

This study aims to offer new insights and perspective into the linear and nonlinear rheology of a wormlike micellar solution containing a well known surfactant, cetylpyridinium chloride, and a binding salt, diclofenac sodium. The wormlike micelles (WLMs) mesoscopic lengths were evaluated through rheology. The micrometer long micelles, disclosed also with cryogenic -Electron Microscopy (cryo-EM), were subjected to start-up flow experiments, both with a rotational rheometer and with a linear strain controlled shear cell coupled with a microscope. In the nonlinear regime, two Weissenberg numbers can be defined, one related to the terminal relaxation time, Wid, and one connected to the breaking and reforming time, Wib. When Wid<1, the measured stress response is monotonically increasing up to a steady state value, and the resulting velocity profile is stable. When Wid>1, the WLMs behave as polymer chains in fast flows, aligning and stretching in the flow direction. When a characteristic shear rate is reached, WLMs show a very pronounced strain hardening behavior, with a stress peak typical of an elastic chain response. When Wib>>1, the stress peak appears at the same strain units above a characteristic shear rate value. A sudden stress decrease manifests after the peak, suggesting a breakage phenomenon. The strain at which the stress peak appears permits the evaluation of the WLMs scission energy. The reconstruction of the velocity profiles along the gap of the sample, thanks to a home made rheo-optical device, and the complete flow curve of the system, built with the help of a bio-printer used as a capillary rheometer, suggest that a shear banding phenomenon appears when Wid is roughly equal to one. No direct connection between banding and scission has been experimentally found.

Non-hydrogen bonding van der Waals liquids with dipole-dipole interactions are typically viewed as non-associative and not considered able to sustain large supramolecular structures. Combining broadband dielectric spectroscopy (BDS) and rheology, we demonstrate the supramolecular formation in a group of non-hydrogen bonding van der Waals liquids, i.e., 1-bromo-2-ethylhexane, 1-chloro-2-ethylhexane, and 1-bromo-3,7-dimethyloctane. BDS shows an emergence of a Debye-like process slower than their structural relaxation, which follows super-Arrhenius temperature dependence. Meanwhile, rheological measurements reveal a noticeable dynamical separation between the terminal relaxation and the structural rearrangements. Interestingly, the rheological terminal time agrees remarkably well with the dielectric Debye-like relaxation time, pointing to a strong coupling between the terminal flow and the supramolecular dynamics of these van der Waals liquids. These results highlight a key role of intermolecular dipole-dipole interaction in the supramolecular structure formation and the slow dynamics of van der Waals liquids.

BackgroundDepression is a significant contributor to the burden of disease globally and is often associated with reduced work productivity and permanent disability.ObjectivesThis study aimed to identify factors associated with return to work among disability claimants with depression at one insurer in South Africa.MethodA retrospective cohort study was conducted with 514 disability claims. Univariate tests for association (Chi-square and Fisher) were performed to test the significance of the association between the primary outcome (disability benefit terminated as a result of return to work) and demographic and workplace factors.ResultsThe majority of disability claimants were women (71.6%). Women and claimants under the age of 60 years at the time of benefit termination had a high probability of returning to work, 80% and 99% respectively. Of the 39% of claimants who had a high level of workplace support during the disability process, 95% also returned to work. Nearly half (48%) of the disability claimants returned to work in less than 6 months, while most of those with a duration of disability longer than 24 months did not return to work (79%).ConclusionFemale gender, lower age (under 60 years), high workplace support and shorter duration of disability were all positively associated with return to work for disability claimants with depression.ContributionThis study provides insights into factors associated with successful return to work for disability claimants with depression, which can guide case management and rehabilitation for this population.

The static and dynamic properties of a cyclic Rouse chain modified by the introduction of an effective, spherically symmetric, attracting potential of entropic nature are studied. It is shown that a relatively weak potential can lead to a strong contraction of the polymer chain: the radius of gyration becomes much smaller compared to the size of the free cyclic chain. The pronounced decrease in the terminal relaxation time of cyclic macromolecules in the presence of a harmonic potential compared to the Rouse relaxation time leads to a lengthening of the time interval for the transition to the normal, i.e., the Fickian, diffusion regime, generating a quasi-plateau at increasing molecular mass for the time dependence of segmental mean squared displacement.

Wearable health assessment devices enable real-time clinical- and home-based patient monitoring. Human gait analysis is a widely accepted musculoskeletal assessment. The 30 s Sit-to-Stand (STS) and Timed-Up-and-Go (TUG) are clinical frailty assessments used alongside gait analysis. This study assessed the reliability and validity of the MoveLab® (Agile Kinetic 2024) approach to measure gait spatiotemporal parameters (STPs), STS, and TUG using a waist-worn mobile phone, compared to the Gold Standard 3D marker-based motion capture (Qualisys AB, Sweden) and the Clinical Standard assessment of the STS and TUG test methods. Movement data, recorded simultaneously for 25 healthy volunteers (14 female and 11 male, Age = 31.8 ± 11.6 yrs) in a Biomechanics Laboratory using the Gold Standard system, the Clinical Standard assessments, and MoveLab®, was analyzed using Intraclass Correlation (ICC) and Bland–Altman plots (Python) to quantify the correlations, consistency, and significance across the output parameters. Comparing the methods, the STP consistency ranged from acceptable to good for all the tested parameters (ICC 0.299–0.894). The highest and lowest correlations were cycle time and terminal double support time, respectively. The TUG showed good agreement (ICC 0.757). Generally, an equal number of MoveLab® STS repetitions were observed. MoveLab® demonstrated validity and reliability for a range of key movement parameters using a pouch-worn mobile phone device in healthy adults in a controlled laboratory environment.

Cardiac models are examples of excitable systems and can support stable spiral waves. For certain parameter values, however, these spiral waves can become unstable, resulting in spiral defect chaos (SDC), characterized by the continuous creation and annihilation of spiral waves and thought to underlie atrial fibrillation. During SDC, the number of spiral waves fluctuates and drops to zero at termination. In this work, we demonstrate that varying a single parameter allows the system to transition from SDC to a single spiral wave, passing through an intermediate regime of intermittency. In such intermittent dynamics, intervals of SDC are sandwiched between non-SDC intervals during which the number of spiral waves remains small and constant. We quantify this intermittency and show that the mean termination time increases significantly as the control parameter approaches values for which a single spiral wave is stable. In addition, we observe that quasistable spiral waves may intermittently persist in part of the computational domain, while the rest of the domain exhibits SDC. Our results may have implications for clinical atrial fibrillation, which often shows intermittency, switching back-and-forth between fibrillation and normal sinus rhythm.

ABSTRACTObjectiveTo examine the association between the introduction of the fetal anomaly scans in the Netherlands and termination of pregnancy (TOP) in cases of prenatally detected upper limb anomalies.MethodsWe conducted a retrospective study among prenatally detected upper limb anomalies between 2000 and 2023. Anomalies were categorized as reduction defects, syndactyly, or polydactyly, and classified as isolated or non‐isolated. We analyzed TOP rates across three periods (2000–2006, 2007–August 2021, September 2021–2023), including an interrupted time series (ITS) analysis to assess the impact of introducing second‐ and first‐trimester anomaly scans (STAS, FTAS).ResultsWe included 300 pregnancies, of which 133 (44.3%) were isolated. Overall TOP rates did not differ significantly between periods, except for isolated reduction defects, where a significant increase was observed (p = 0.032). TOP rates over time did not increase for syndactyly and polydactyly. Median gestational age at diagnosis decreased across the three periods: from 20.4 to 19.4 weeks and then to 14.9 weeks. Similarly, the timing of termination of pregnancy decreased from 20.5 to 16.8 weeks and then to 15.0 weeks.ConclusionEarlier prenatal detection followed the introduction of STAS and FTAS. Despite this shift in timing, no consistent changes in termination rates were observed across the study periods. While overall TOP rates remained stable, a trend towards higher termination rates was observed for isolated reduction defects.

Excitable media, including a cardiac tissue, can exhibit spiral defect chaos (SDC), during which spiral waves are continuously created and annihilated. Simulating this behavior typically requires solving large-scale reaction-diffusion systems, limiting computational feasibility especially for larger model domains. To address this, we have previously developed a particle model that was capable of replicating spiral-wave annihilation via short-range attraction and diffusion. In this study, we extend that model to capture spiral-wave creation by introducing a short-lived repulsive interaction between newly formed particle pairs. Our extended model accurately reproduces the termination statistics of SDC in cardiac simulations, including mean termination time, offering a simplified yet faithful description of SDC dynamics at much lesser computational cost.

Stochastic Maximum Principle for Optimal Control Problem with Varying Terminal Time and Non-convex Control Domain