Complementary approaches to understanding the plant circadian clock

Circadian clocks are oscillatory genetic networks that help organisms adapt to the 24-hour day/night cycle. The clock of the green alga Ostreococcus tauri is the simplest plant clock discovered so far. Its many advantages as an experimental system facilitate the testing of computational predictions. We present a model of the Ostreococcus clock in the stochastic process algebra Bio-PEPA and exploit its mapping to different analysis techniques, such as ordinary differential equations, stochastic simulation algorithms and model-checking. The small number of molecules reported for this system tests the limits of the continuous approximation underlying differential equations. We investigate the difference between continuous-deterministic and discrete-stochastic approaches. Stochastic simulation and model-checking allow us to formulate new hypotheses on the system behaviour, such as the presence of self-sustained oscillations in single cells under constant light conditions. We investigate how to model the timing of dawn and dusk in the context of model-checking, which we use to compute how the probability distributions of key biochemical species change over time. These show that the relative variation in expression level is smallest at the time of peak expression, making peak time an optimal experimental phase marker. Building on these analyses, we use approaches from evolutionary systems biology to investigate how changes in the rate of mRNA degradation impacts the phase of a key protein likely to affect fitness. We explore how robust this circadian clock is towards such potential mutational changes in its underlying biochemistry. Our work shows that multiple approaches lead to a more complete understanding of the clock

Analysing nystagmus waveforms: a computational framework

We present a new computational approach to analyse nystagmus waveforms. Our framework is designed to fully characterise the state of the nystagmus, aid clinical diagnosis and to quantify the dynamical changes in the oscillations over time. Both linear and nonlinear analyses of time series were used to determine the regularity and complexity of a specific homogenous phenotype of nystagmus. Two-dimensional binocular eye movement recordings were carried out on 5 adult subjects who exhibited a unilateral, uniplanar, vertical nystagmus secondary to a monocular late-onset severe visual loss in the oscillating eye (the Heimann-Bielschowsky Phenomenon). The non-affected eye held a central gaze in both horizontal and vertical planes (± 10 min. of arc). All affected eyes exhibited vertical oscillations, with mean amplitudes and frequencies ranging from 2.0°–4.0° to 0.25–1.5 Hz, respectively. Unstable periodic orbit analysis revealed only 1 subject exhibited a periodic oscillation. The remaining subjects were found to display quasiperiodic (n = 1) and nonperiodic (n = 3) oscillations. Phase space reconstruction allowed attractor identification and the computation of a time series complexity measure—the permutation entropy. The entropy measure was found to be able to distinguish between a periodic oscillation associated with a limit cycle attractor, a quasiperiodic oscillation associated with a torus attractor and nonperiodic oscillations associated with higher-dimensional attractors. Importantly, the permutation entropy was able to rank the oscillations, thereby providing an objective index of nystagmus complexity (range 0.15–0.21) that could not be obtained via unstable periodic orbit analysis or attractor identification alone. These results suggest that our framework provides a comprehensive methodology for characterising nystagmus, aiding differential diagnosis and also permitting investigation of the waveforms over time, thereby facilitating the quantification of future therapeutic managements. In addition, permutation entropy could provide an additional tool for future oculomotor modelling

Modelling Non-linear Crowd Dynamics in Bio-PEPA

Emergent phenomena occur due to the pattern of non-linear and distributed local interactions between the elements of a system over time. Surprisingly, agent based crowd models, in which the movement of each individual follows a limited set of simple rules, often re-produce quite closely the emergent behaviour of crowds that can be observed in reality. An example of such phenomena is the spontaneous self-organisation of drinking parties in the squares of cities in Spain, also known as "El Botellon" [20]. We revisit this case study providing an elegant stochastic process algebraic model in Bio-PEPA amenable to several forms of analyses, among which simulation and fluid flow analysis. We show that a fluid flow approximation, i.e. a deterministic reading of the average behaviour of the system, can provide an alternative and efficient way to study the same emergent behaviour as that explored in [20] where simulation was used instead. Besides empirical evidence, also an analytical justification is provided for the good correspondence found between simulation results and the fluid flow approximation

Exploring Nurses’ Meaning and Experiences of Compassion: An International Online Survey Involving 15 Countries

Purpose: In recent years, there has been much focus on compassion in nursing care, and concern has been raised in a number of reports and media stories regarding decreased compassion. The aim of this study was to explore similarities and differences in the understanding and demonstration of compassion in nursing practice across 15 countries. Design: A total of 1,323 nurses from 15 countries responded to questions in relation to compassion, via an international online survey. Results: The data revealed the impact of sociopolitical influences on perceptions of compassion, and the conscious and intentional nature of compassion. Discussion and Conclusion: The study demonstrated shared understandings of the importance of compassion as well as some common perceptions of the attributes of compassionate care. The differences reported were not as significant as had been expected. Implications for Practice: Further research is needed to explore the country and culture differences in the enactment of compassion. © 2015, © The Author(s) 2015