Global Hopf bifurcation in the ZIP regulatory system

Regulation of zinc uptake in roots of Arabidopsis thaliana has recently been modeled by a system of ordinary differential equations based on the uptake of zinc, expression of a transporter protein and the interaction between an activator and inhibitor. For certain parameter choices the steady state of this model becomes unstable upon variation in the external zinc concentration. Numerical results show periodic orbits emerging between two critical values of the external zinc concentration. Here we show the existence of a global Hopf bifurcation with a continuous family of stable periodic orbits between two Hopf bifurcation points. The stability of the orbits in a neighborhood of the bifurcation points is analyzed by deriving the normal form, while the stability of the orbits in the global continuation is shown by calculation of the Floquet multipliers. From a biological point of view, stable periodic orbits lead to potentially toxic zinc peaks in plant cells. Buffering is believed to be an efficient way to deal with strong transient variations in zinc supply. We extend the model by a buffer reaction and analyze the stability of the steady state in dependence of the properties of this reaction. We find that a large enough equilibrium constant of the buffering reaction stabilizes the steady state and prevents the development of oscillations. Hence, our results suggest that buffering has a key role in the dynamics of zinc homeostasis in plant cells.Comment: 22 pages, 5 figures, uses svjour3.cl

Simulation-based training of the rapid evaluation and management of acute stroke (stream)—a prospective single-arm multicenter trial

Introduction: Acute stroke care delivered by interdisciplinary teams is time-sensitive. Simulation-based team training is a promising tool to improve team performance in medical operations. It has the potential to improve process times, team communication, patient safety, and staff satisfaction. We aim to assess whether a multi-level approach consisting of a stringent workflow revision based on peer-to-peer review and 2–3 one-day in situ simulation trainings can improve acute stroke care processing times in high volume neurocenters within a 6 months period. Methods and Analysis: The trial is being carried out in a pre-test-post-test design at 7 tertiary care university hospital neurocenters in Germany. The intervention is directed at the interdisciplinary multiprofessional stroke teams. Before and after the intervention, process times of all direct-to-center stroke patients receiving IV thrombolysis (IVT) and/or endovascular therapy (EVT) will be recorded. The primary outcome measure will be the “door-to-needle” time of all consecutive stroke patients directly admitted to the neurocenters who receive IVT. Secondary outcome measures will be intervention-related process times of the fraction of patients undergoing EVT and effects on team communication, perceived patient safety, and staff satisfaction via a staff questionnaire. Interventions: We are applying a multi-level intervention in cooperation with three “STREAM multipliers” from each center. First step is a central meeting of the multipliers at the sponsor's institution with the purposes of algorithm review in a peer-to-peer process that is recorded in a protocol and an introduction to the principles of simulation training and debriefing as well as crew resource management and team communication. Thereafter, the multipliers cooperate with the stroke team trainers from the sponsor's institution to plan and execute 2–3 one-day simulation courses in situ in the emergency department and CT room of the trial centers whereupon they receive teaching materials to perpetuate the trainings. Clinical Trial Registration: STREAM is a registered trial at https://clinicaltrials.gov/ct2/show/NCT03228251

Simulation‐based training improves process times in acute stroke care (STREAM)

Background The objective of the STREAM Trial was to evaluate the effect of simulation training on process times in acute stroke care. Methods The multicenter prospective interventional STREAM Trial was conducted between 10/2017 and 04/2019 at seven tertiary care neurocenters in Germany with a pre- and post-interventional observation phase. We recorded patient characteristics, acute stroke care process times, stroke team composition and simulation experience for consecutive direct-to-center patients receiving intravenous thrombolysis (IVT) and/or endovascular therapy (EVT). The intervention consisted of a composite intervention centered around stroke-specific in situ simulation training. Primary outcome measure was the 'door-to-needle' time (DTN) for IVT. Secondary outcome measures included process times of EVT and measures taken to streamline the pre-existing treatment algorithm. Results The effect of the STREAM intervention on the process times of all acute stroke operations was neutral. However, secondary analyses showed a DTN reduction of 5 min from 38 min pre-intervention (interquartile range [IQR] 25-43 min) to 33 min (IQR 23-39 min, p = 0.03) post-intervention achieved by simulation-experienced stroke teams. Concerning EVT, we found significantly shorter door-to-groin times in patients who were treated by teams with simulation experience as compared to simulation-naive teams in the post-interventional phase (-21 min, simulation-naive: 95 min, IQR 69-111 vs. simulation-experienced: 74 min, IQR 51-92, p = 0.04). Conclusion An intervention combining workflow refinement and simulation-based stroke team training has the potential to improve process times in acute stroke care

Simulation-Based Training of the Rapid Evaluation and Management of Acute Stroke (STREAM)-A Prospective Single-Arm Multicenter Trial

Introduction: Acute stroke care delivered by interdisciplinary teams is time-sensitive. Simulation-based team training is a promising tool to improve team performance in medical operations. It has the potential to improve process times, team communication, patient safety, and staff satisfaction. We aim to assess whether a multi-level approach consisting of a stringent workflow revision based on peer-to-peer review and 2-3 one-day in situ simulation trainings can improve acute stroke care processing times in high volume neurocenters within a 6 months period. Methods and Analysis: The trial is being carried out in a pre-test-post-test design at 7 tertiary care university hospital neurocenters in Germany. The intervention is directed at the interdisciplinary multiprofessional stroke teams. Before and after the intervention, process times of all direct-to-center stroke patients receiving IV thrombolysis (IVT) and/or endovascular therapy (EVT) will be recorded. The primary outcome measure will be the door-to-needle time of all consecutive stroke patients directly admitted to the neurocenters who receive IVT. Secondary outcome measures will be intervention-related process times of the fraction of patients undergoing EVT and effects on team communication, perceived patient safety, and staff satisfaction via a staff questionnaire. Interventions: We are applying a multi-level intervention in cooperation with three STREAM multipliers from each center. First step is a central meeting of the multipliers at the sponsor's institution with the purposes of algorithm review in a peer-to-peer process that is recorded in a protocol and an introduction to the principles of simulation training and debriefing as well as crew resource management and team communication. Thereafter, the multipliers cooperate with the stroke team trainers from the sponsor's institution to plan and execute 2-3 one-day simulation courses in situ in the emergency department and CT room of the trial centers whereupon they receive teaching materials to perpetuate the trainings