An Actor-Critic based controller for glucose regulation in type 1 diabetes

A novel adaptive approach for glucose control in individuals with type 1 diabetes under sensor-augmented pump therapy is proposed. The controller, is based on Actor-Critic (AC) learning and is inspired by the principles of reinforcement learning and optimal control theory. The main characteristics of the proposed controller are (i) simultaneous adjustment of both the insulin basal rate and the bolus dose, (ii) initialization based on clinical procedures, and (iii) real-time personalization. The effectiveness of the proposed algorithm in terms of glycemic control has been investigated in silico in adults, adolescents and children under open-loop and closed-loop approaches, using announced meals with uncertainties in the order of ±25% in the estimation of carbohydrates. The results show that glucose regulation is efficient in all three groups of patients, even with uncertainties in the level of carbohydrates in the meal. The percentages in the A+B zones of the Control Variability Grid Analysis (CVGA) were 100% for adults, and 93% for both adolescents and children. The AC based controller seems to be a promising approach for the automatic adjustment of insulin infusion in order to improve glycemic control. After optimization of the algorithm, the controller will be tested in a clinical trial.

Defence on demand: mechanisms behind optimal defence patterns

Background The optimal defence hypothesis (ODH) predicts that tissues that contribute most to a plant's fitness and have the highest probability of being attacked will be the parts best defended against biotic threats, including herbivores. In general, young sink tissues and reproductive structures show stronger induced defence responses after attack from pathogens and herbivores and contain higher basal levels of specialized defensive metabolites than other plant parts. However, the underlying physiological mechanisms responsible for these developmentally regulated defence patterns remain unknown. Scope This review summarizes current knowledge about optimal defence patterns in above- and below-ground plant tissues, including information on basal and induced defence metabolite accumulation, defensive structures and their regulation by jasmonic acid (JA). Physiological regulations underlying developmental differences of tissues with contrasting defence patterns are highlighted, with a special focus on the role of classical plant growth hormones, including auxins, cytokinins, gibberellins and brassinosteroids, and their interactions with the JA pathway. By synthesizing recent findings about the dual roles of these growth hormones in plant development and defence responses, this review aims to provide a framework for new discoveries on the molecular basis of patterns predicted by the ODH. Conclusions Almost four decades after its formulation, we are just beginning to understand the underlying molecular mechanisms responsible for the patterns of defence allocation predicted by the ODH. A requirement for future advances will be to understand how developmental and defence processes are integrated.