A resonant sextuplet of sub-Neptunes transiting the bright star HD 110067.

Planets with radii between that of the Earth and Neptune (hereafter referred to as 'sub-Neptunes') are found in close-in orbits around more than half of all Sun-like stars1,2. However, their composition, formation and evolution remain poorly understood3. The study of multiplanetary systems offers an opportunity to investigate the outcomes of planet formation and evolution while controlling for initial conditions and environment. Those in resonance (with their orbital periods related by a ratio of small integers) are particularly valuable because they imply a system architecture practically unchanged since its birth. Here we present the observations of six transiting planets around the bright nearby star HD 110067. We find that the planets follow a chain of resonant orbits. A dynamical study of the innermost planet triplet allowed the prediction and later confirmation of the orbits of the rest of the planets in the system. The six planets are found to be sub-Neptunes with radii ranging from 1.94R⊕ to 2.85R⊕. Three of the planets have measured masses, yielding low bulk densities that suggest the presence of large hydrogen-dominated atmospheres.

[Development of a new closed-loop system for controlling mivacurium-induced neuromuscular blockade]. / Entwicklung eines neuen Closed-Loop Systems. Regelung einer Mivacurium-induzierten neuromuskulären Blockade.

UNLABELLED: There are many closed-loop control systems for muscle relaxants reported, but only a few could cope with the introduction of the latest shorter acting neuromuscular blocking drugs. These new muscle relaxants such as mivacurium require a fast adapting closed-loop system for controlling an adequate infusion. METHODS: After approval of the local ethics committee and having the patients' informed consent a total number of 75 patients [ASA I and II] were included in the study and assigned either to a training-, prediction-, prediction-/feedback- or a validation phase, as needed. Anaesthesia was induced and maintained with propofol in a TCI-mode with a plasma level of 3 to 5 micrograms/ml and 0.1 mg fentanyl boli as needed in all patients. In the last validation phase, having 20 patients, the prediction error and the error of the whole system was taken and analysed. RESULTS: A closed-loop system using a neural network as a predictor could be established. In the final validation phase consisting of 20 patients the mean square prediction error was found to be 0.1% +/- 0.2% [mean +/- SD]. The mean square error of the whole system was 0.55% +/- 0.59% [mean +/- SD]. CONCLUSIONS: A closed-loop system for control of a mivacurium infusion could be established. The system proofed to be reliable for a closed-loop infusion of mivacurium in order to maintain a predefined degree of neuromuscular blockade of 95% during routine surgery. The performance of the described controller is comparable to all recent attempts and could therefore be useful for scientific studies. It should be further validated and established for other muscle relaxants, as well.

Nonlinear model-based predictive control of non-depolarizing muscle relaxants using neural networks.

Neuromuscular blockade can be relatively easily measured in the clinical setting. Consequently, closed-loop control can be exercised by measuring the neuromuscular activity, calculating the dose of drug necessary to achieve a predefined degree of neuromuscular blockade and finally directing an infusion pump. Recently introduced short-acting blocking agents like mivacurium provide benefits for the clinical routine due to a small onset time and half life. In order to provide a stable blockade for different groups of patients a fast and highly adaptable control unit is needed. Furthermore its development should not imply costly investigations for determining a pharmacological model. The fulfilling of these requirements yield a self-adapting model-based predictive control system. The application of artificial neural networks allows an appropriate adjustment of specific parameters without the knowledge of inner pharmacodynamic processes. In a clinical study the EMG module within a Datex AS/3 monitor was used to measure the blockade and a Grasepy 3500 infusion pump for i.v. administration of mivacurium to 35 patients (ASA I-III). The performance of the novel system (mean of the T1 error: -0.32 +/- 1.7) compares favourably with closed-loop controllers demonstrated in the past. These promising results and the easy adaption to other blocking agents encourage to apply this technology even for delivering hypnotic drugs.