An insulin infusion advisory system based on autotuning nonlinear model-predictive control

This paper aims at the development and evaluation of a personalized insulin infusion advisory system (IIAS), able to provide real-time estimations of the appropriate insulin infusion rate for type 1 diabetes mellitus (T1DM) patients using continuous glucose monitors and insulin pumps. The system is based on a nonlinear model-predictive controller (NMPC) that uses a personalized glucose-insulin metabolism model, consisting of two compartmental models and a recurrent neural network. The model takes as input patient's information regarding meal intake, glucose measurements, and insulin infusion rates, and provides glucose predictions. The predictions are fed to the NMPC, in order for the latter to estimate the optimum insulin infusion rates. An algorithm based on fuzzy logic has been developed for the on-line adaptation of the NMPC control parameters. The IIAS has been in silico evaluated using an appropriate simulation environment (UVa T1DM simulator). The IIAS was able to handle various meal profiles, fasting conditions, interpatient variability, intraday variation in physiological parameters, and errors in meal amount estimations.

Model-based control of neuromuscular block using mivacurium: design and clinical verification

BACKGROUND: Short-acting agents for neuromuscular block (NMB) require frequent dosing adjustments for individual patient's needs. In this study, we verified a new closed-loop controller for mivacurium dosing in clinical trials. METHODS: Fifteen patients were studied. T1% measured with electromyography was used as input signal for the model-based controller. After induction of propofol/opiate anaesthesia, stabilization of baseline electromyography signal was awaited and a bolus of 0.3 mg kg-1 mivacurium was then administered to facilitate endotracheal intubation. Closed-loop infusion was started thereafter, targeting a neuromuscular block of 90%. Setpoint deviation, the number of manual interventions and surgeon's complaints were recorded. Drug use and its variability between and within patients were evaluated. RESULTS: Median time of closed-loop control for the 11 patients included in the data processing was 135 [89-336] min (median [range]). Four patients had to be excluded because of sensor problems. Mean absolute deviation from setpoint was 1.8 +/- 0.9 T1%. Neither manual interventions nor complaints from the surgeons were recorded. Mean necessary mivacurium infusion rate was 7.0 +/- 2.2 microg kg-1 min-1. Intrapatient variability of mean infusion rates over 30-min interval showed high differences up to a factor of 1.8 between highest and lowest requirement in the same patient. CONCLUSIONS: Neuromuscular block can precisely be controlled with mivacurium using our model-based controller. The amount of mivacurium needed to maintain T1% at defined constant levels differed largely between and within patients. Closed-loop control seems therefore advantageous to automatically maintain neuromuscular block at constant levels.

An insulin infusion advisory system for type 1 diabetes patients based on non-linear model predictive control methods

In this paper, an Insulin Infusion Advisory System (IIAS) for Type 1 diabetes patients, which use insulin pumps for the Continuous Subcutaneous Insulin Infusion (CSII) is presented. The purpose of the system is to estimate the appropriate insulin infusion rates. The system is based on a Non-Linear Model Predictive Controller (NMPC) which uses a hybrid model. The model comprises a Compartmental Model (CM), which simulates the absorption of the glucose to the blood due to meal intakes, and a Neural Network (NN), which simulates the glucose-insulin kinetics. The NN is a Recurrent NN (RNN) trained with the Real Time Recurrent Learning (RTRL) algorithm. The output of the model consists of short term glucose predictions and provides input to the NMPC, in order for the latter to estimate the optimum insulin infusion rates. For the development and the evaluation of the IIAS, data generated from a Mathematical Model (MM) of a Type 1 diabetes patient have been used. The proposed control strategy is evaluated at multiple meal disturbances, various noise levels and additional time delays. The results indicate that the implemented IIAS is capable of handling multiple meals, which correspond to realistic meal profiles, large noise levels and time delays.

Integrated care in patients with schizophrenia: results of trials published between 2011 and 2013 focusing on effectiveness and efficiency

Purpose of review: Overview on integrated care trials focusing on effectiveness and efficiency published from 2011 to 2013. Recent findings: Eight randomized controlled trials (RCTs) and 21 non-RCT studies were published from 2011 to 2013. Studies differed in several methodological aspects such as study population, psychotherapeutic approaches used, outcome parameters, follow-up times, fidelities, and implementation of the integrated care model and the nation-specific healthcare context with different control conditions. This makes it difficult to draw firm conclusions. Most studies demonstrated relevant improvements regarding symptoms (P = 0.001) and functioning (P = 0.01), quality of life (P = 0.01), adherence (P <0.05) and patient's satisfaction (P = 0.01), and reduction of caregiver's stress (P < 0.05). Mean total costs were favoring or at least equalizing costs but with positive effects found on subjective health favoring integrated care models. Summary: There is an increasing interest in the effectiveness and efficiency of integrated care models in patients with mental disorders, specifically in those with severe and persistent mental illness. To increase generalizability, future trials should exactly describe rationales and content of integrated care model and control conditions.

Closed-loop control of mean arterial blood pressure during surgery with alfentanil: clinical evaluation of a novel model-based predictive controller

BACKGROUND: In contrast to hypnosis, there is no surrogate parameter for analgesia in anesthetized patients. Opioids are titrated to suppress blood pressure response to noxious stimulation. The authors evaluated a novel model predictive controller for closed-loop administration of alfentanil using mean arterial blood pressure and predicted plasma alfentanil concentration (Cp Alf) as input parameters. METHODS: The authors studied 13 healthy patients scheduled to undergo minor lumbar and cervical spine surgery. After induction with propofol, alfentanil, and mivacurium and tracheal intubation, isoflurane was titrated to maintain the Bispectral Index at 55 (+/- 5), and the alfentanil administration was switched from manual to closed-loop control. The controller adjusted the alfentanil infusion rate to maintain the mean arterial blood pressure near the set-point (70 mmHg) while minimizing the Cp Alf toward the set-point plasma alfentanil concentration (Cp Alfref) (100 ng/ml). RESULTS: Two patients were excluded because of loss of arterial pressure signal and protocol violation. The alfentanil infusion was closed-loop controlled for a mean (SD) of 98.9 (1.5)% of presurgery time and 95.5 (4.3)% of surgery time. The mean (SD) end-tidal isoflurane concentrations were 0.78 (0.1) and 0.86 (0.1) vol%, the Cp Alf values were 122 (35) and 181 (58) ng/ml, and the Bispectral Index values were 51 (9) and 52 (4) before surgery and during surgery, respectively. The mean (SD) absolute deviations of mean arterial blood pressure were 7.6 (2.6) and 10.0 (4.2) mmHg (P = 0.262), and the median performance error, median absolute performance error, and wobble were 4.2 (6.2) and 8.8 (9.4)% (P = 0.002), 7.9 (3.8) and 11.8 (6.3)% (P = 0.129), and 14.5 (8.4) and 5.7 (1.2)% (P = 0.002) before surgery and during surgery, respectively. A post hoc simulation showed that the Cp Alfref decreased the predicted Cp Alf compared with mean arterial blood pressure alone. CONCLUSION: The authors' controller has a similar set-point precision as previous hypnotic controllers and provides adequate alfentanil dosing during surgery. It may help to standardize opioid dosing in research and may be a further step toward a multiple input-multiple output controller.

Predicting asthma control and exacerbations: chronic asthma as a complex dynamic model

PURPOSE OF REVIEW: Predicting asthma episodes is notoriously difficult but has potentially significant consequences for the individual, as well as for healthcare services. The purpose of this review is to describe recent insights into the prediction of acute asthma episodes in relation to classical clinical, functional or inflammatory variables, as well as present a new concept for evaluating asthma as a dynamically regulated homeokinetic system. RECENT FINDINGS: Risk prediction for asthma episodes or relapse has been attempted using clinical scoring systems, considerations of environmental factors and lung function, as well as inflammatory and immunological markers in induced sputum or exhaled air, and these are summarized here. We have recently proposed that newer mathematical methods derived from statistical physics may be used to understand the complexity of asthma as a homeokinetic, dynamic system consisting of a network comprising multiple components, and also to assess the risk for future asthma episodes based on fluctuation analysis of long time series of lung function. SUMMARY: Apart from the classical analysis of risk factor and functional parameters, this new approach may be used to assess asthma control and treatment effects in the individual as well as in future research trials.

Basic control of reperfusion effectively protects against reperfusion injury in a realistic rodent model of acute limb ischemia

BACKGROUND: Reperfusion injury is insufficiently addressed in current clinical management of acute limb ischemia. Controlled reperfusion carries an enormous clinical potential and was tested in a new reality-driven rodent model. METHODS AND RESULTS: Acute hind-limb ischemia was induced in Wistar rats and maintained for 4 hours. Unlike previous tourniquets models, femoral vessels were surgically prepared to facilitate controlled reperfusion and to prevent venous stasis. Rats were randomized into an experimental group (n=7), in which limbs were selectively perfused with a cooled isotone heparin solution at a limited flow rate before blood flow was restored, and a conventional group (n=7; uncontrolled blood reperfusion). Rats were killed 4 hours after blood reperfusion. Nonischemic limbs served as controls. Ischemia/reperfusion injury was significant in both groups; total wet-to-dry ratio was 159+/-44% of normal (P=0.016), whereas muscle viability and contraction force were reduced to 65+/-13% (P=0.016) and 45+/-34% (P=0.045), respectively. Controlled reperfusion, however, attenuated reperfusion injury significantly. Tissue edema was less pronounced (132+/-16% versus 185+/-42%; P=0.011) and muscle viability (74+/-11% versus 57+/-9%; P=0.004) and contraction force (68+/-40% versus 26+/-7%; P=0.045) were better preserved than after uncontrolled reperfusion. Moreover, subsequent blood circulation as assessed by laser Doppler recovered completely after controlled reperfusion but stayed durably impaired after uncontrolled reperfusion (P=0.027). CONCLUSIONS: Reperfusion injury was significantly alleviated by basic modifications of the initial reperfusion period in a new in vivo model of acute limb ischemia. With this model, systematic optimizations of according protocols may eventually translate into improved clinical management of acute limb ischemia.

Evaluation of control and surveillance strategies for classical swine fever using a simulation model

Classical swine fever (CSF) outbreaks can cause enormous losses in naïve pig populations. How to best minimize the economic damage and number of culled animals caused by CSF is therefore an important research area. The baseline CSF control strategy in the European Union and Switzerland consists of culling all animals in infected herds, movement restrictions for animals, material and people within a given distance to the infected herd and epidemiological tracing of transmission contacts. Additional disease control measures such as pre-emptive culling or vaccination have been recommended based on the results from several simulation models; however, these models were parameterized for areas with high animal densities. The objective of this study was to explore whether pre-emptive culling and emergency vaccination should also be recommended in low- to moderate-density areas such as Switzerland. Additionally, we studied the influence of initial outbreak conditions on outbreak severity to improve the efficiency of disease prevention and surveillance. A spatial, stochastic, individual-animal-based simulation model using all registered Swiss pig premises in 2009 (n=9770) was implemented to quantify these relationships. The model simulates within-herd and between-herd transmission (direct and indirect contacts and local area spread). By varying the four parameters (a) control measures, (b) index herd type (breeding, fattening, weaning or mixed herd), (c) detection delay for secondary cases during an outbreak and (d) contact tracing probability, 112 distinct scenarios were simulated. To assess the impact of scenarios on outbreak severity, daily transmission rates were compared between scenarios. Compared with the baseline strategy (stamping out and movement restrictions) vaccination and pre-emptive culling neither reduced outbreak size nor duration. Outbreaks starting in a herd with weaning piglets or fattening pigs caused higher losses regarding to the number of culled premises and were longer lasting than those starting in the two other index herd types. Similarly, larger transmission rates were estimated for these index herd type outbreaks. A longer detection delay resulted in more culled premises and longer duration and better transmission tracing increased the number of short outbreaks. Based on the simulation results, baseline control strategies seem sufficient to control CSF in low-medium animal-dense areas. Early detection of outbreaks is crucial and risk-based surveillance should be focused on weaning piglet and fattening pig premises.

Examining Gender Differences in Received, Provided and Invisible Social Control: An Application of the Dual-Effects-Model

The dual-effects model of social control not only assumes that social control leads to better health practices but also arouses psychological distress. However, findings are inconsistent. The present study advances the current literature by examining social control from a dyadic perspective in the context of smoking. In addition, the study examines whether control, continuous smoking abstinence, and affect are differentially related for men and women. Before and three weeks after a self-set quit attempt, we examined 106 smokers (77 men, mean age: 40.67, average number of cigarettes smoked per day: 16.59 [SD=8.52, range=1-40] at baseline and 5.27 [SD=6.97, range=0-40] at follow-up) and their nonsmoking heterosexual partners, assessing received and provided control, continuous abstinence, and affect. With regard to smoker's affective reactions, partner's provided control was related to an increase in positive and to a decrease in negative affect, but only for female smokers. Moreover, the greater the discrepancy between smoker received and partner's provided control was the more positive affect increased and the more negative affect decreased, but again only for female smokers. These findings demonstrate that female smokers' well-being was raised over time if they were not aware of the control attempts of their nonsmoking partners, indicating positive effects of invisible social control. This study's results emphasize the importance of applying a dyadic perspective and taking gender differences in the dual-effects model of social control into account.

Integrating attentional control theory and the strength model of self-control

In the present article, we argue that it may be fruitful to incorporate the ideas of the strength model of self-control into the core assumptions of the well-established attentional control theory (ACT). In ACT, it is assumed that anxiety automatically leads to attention disruption and increased distractibility, which may impair subsequent cognitive or perceptual-motor performance, but only if individuals do not have the ability to counteract this attention disruption. However, ACT does not clarify which process determines whether one can volitionally regulate attention despite experiencing high levels of anxiety. In terms of the strength model of self-control, attention regulation can be viewed as a self-control act depending on the momentary availability of self-control strength. We review literature that has revealed that self-control strength moderates the anxiety-performance relationship, discuss how to integrate these two theoretical models, and offer practical recommendations of how to counteract negative anxiety effects.

Neuroenhancement and the strength model of self-control

Neuroenhancement (NE), the use of substances as a means to enhance performance, has garnered considerable scientific attention of late. While ethical and epidemiological publications on the topic accumulate, there is a lack of theory-driven psychological research that aims at understanding psychological drivers of NE. In this perspective article we argue that self-control strength offers a promising theory-based approach to further understand and investigate NE behavior. Using the strength model of self-control, we derive two theory-driven perspectives on NE-self-control research. First, we propose that individual differences in state/trait self-control strength differentially affect NE behavior based on one’s individual experience of NE use. Building upon this, we outline promising research questions that (will) further elucidate our understanding of NE based on the strength model’s propositions. Second, we discuss evidence indicating that popular NE substances (like Methylphenidate) may counteract imminent losses of self-control strength. We outline how further research on NE’s effects on the ego-depletion effect may further broaden our understanding of the strength model of self-control.

The strengh model of self-control in sport and exercise psychology

The strength model of self-control assumes that all acts of self-control (e.g., emotion regulation, persistence) are empowered by a single global metaphorical strength that has limited capacity. This strength can become temporarily depleted after a primary self-control act, which, in turn, can impair performance in subsequent acts of self-control. Recently, the assumptions of the strength model of self-control also have been adopted and tested in the field of sport and exercise psychology. The present review paper aims to give an overview of recent developments in self-control research based on the strength model of self-control. Furthermore, recent research on interventions on how to improve and revitalize self-control strength will be presented. Finally, the strength model of self-control has been criticized lately, as well as expanded in scope, so the present paper will also discuss alternative explanations of why previous acts of self-control can lead to impaired performance in sport and exercise.