Periodic breathing at high altitude.

Periodic breathing is often associated with heart disease or stroke, and commonly Cheyne-Stokes breathing has a period of about a minute. Periodic breathing also commonly occurs in healthy subjects at high altitude, and here the periods may be much shorter, of the order of 15-20 s. In this paper we study such periodic breathing using the classical model of Grodins et al. (1967, J. Appl. Physiol. 22, 260-276), together with a prescription for the dependence of ventilation on the blood CO2 concentration, modulated by the reduced oxygen pressure (the 'Oxford fan'). The model focusses on the fast dynamics of the arterial blood CO2, and differs in this respect from our previous work which emphasised the brain CO2 concentration; in this sense our model is in fact a generalization of the conceptually simpler Mackey-Glass model

The role of the central chemoreceptor in causing periodic breathing.

In a previous publication (Fowler et aL, 1993), we reduced the classical cardiorespiratory control model of (Grodins et aL, 1967) to a much simpler form, which we then used to study the phenomenon of periodic breathing. In particular, cardiac output was assumed constant, and a single (constant) delay representing arterial blood transport time between lung and brain was included in the model. In this paper we extend this earlier work, both by allowing for the variability in transport delays, due to the dependence of cardiac output on blood gas concentrations, and also by including further delays in the system. In addition, we extensively discuss the physiological implications of parameter variations in the model; several novel mechanisms for periodic breathing in clinical situations are proposed. The results are discussed in the light of recent observational studies. Keywords: Periodic breathing; Cheyne-Stokes respiration; heart-rate variability*, differential-delay equations. 1

Nonlinear oscillations and chaos in chemical cardiorespiratory control

We report progress made on an analytic investigation of low-frequency cardiorespiratory variability in humans. The work is based on an existing physiological model of chemically-mediated blood-gas control via the central and peripheral chemoreceptors, that of Grodins, Buell & Bart (1967). Scaling and simplification of the Grodins model yields a rich variety of dynamical subsets; the thesis focusses on the dynamics obtained under the normoxic assumption (i.e., when oxygen is decoupled from the system). In general, the method of asymptotic reduction yields submodels that validate or invalidate numerous (and more heuristic) extant efforts in the literature. Some of the physiologically-relevant behaviour obtained here has therefore been reported before, but a large number of features are reported for the first time. A particular novelty is the explicit demonstration of cardiorespiratory coupling via chemosensory control. The physiology and literature reviewed in Chapters 1 and 2 set the stage for the investigation. Chapter 3 scales and simplifies the Grodins model; Chapters 4, 5, 6 consider carbon dioxide dynamics at the central chemoreceptor. Chapter 7 begins analysis of the dynamics mediated by the peripheral receptor. Essentially all of the dynamical behaviour is due to the effect of time delays occurring within the conservation relations (which are ordinary differential equations). The pathophysiology highlighted by the analysis is considerable, and includes central nervous system disorders, heart failure, metabolic diseases, lung disorders, vascular pathologies, physiological changes during sleep, and ascent to high altitude. Chapter 8 concludes the thesis with a summary of achievements and directions for further work

Could the 2017 ILAE and the four-dimensional epilepsy classifications be merged to a new "Integrated Epilepsy Classification"?

Over the last few decades the ILAE classifications for seizures and epilepsies (ILAE-EC) have been updated repeatedly to reflect the substantial progress that has been made in diagnosis and understanding of the etiology of epilepsies and seizures and to correct some of the shortcomings of the terminology used by the original taxonomy from the 1980s. However, these proposals have not been universally accepted or used in routine clinical practice. During the same period, a separate classification known as the "Four-dimensional epilepsy classification" (4D-EC) was developed which includes a seizure classification based exclusively on ictal symptomatology, which has been tested and adapted over the years. The extensive arguments for and against these two classification systems made in the past have mainly focused on the shortcomings of each system, presuming that they are incompatible. As a further more detailed discussion of the differences seemed relatively unproductive, we here review and assess the concordance between these two approaches that has evolved over time, to consider whether a classification incorporating the best aspects of the two approaches is feasible. To facilitate further discussion in this direction we outline a concrete proposal showing how such a compromise could be accomplished, the "Integrated Epilepsy Classification". This consists of five categories derived to different degrees from both of the classification systems: 1) a "Headline" summarizing localization and etiology for the less specialized users, 2) "Seizure type(s)", 3) "Epilepsy type" (focal, generalized or unknown allowing to add the epilepsy syndrome if available), 4) "Etiology", and 5) "Comorbidities & patient preferences"