In vitro examination of the effect of Orlistat on the ability of the faecal microbiota to utilize dietary lipids

Orlistat is an anti-obesity treatment with which several gastrointestinal (GI) side-effects are commonly associated in the initial stages of therapy. There is no physiological explanation as to why two-thirds of those who take the drug experience one or more side-effects. It has been hypothesized that the GI microbiota may protect from or contribute to these GI disturbances. Using in vitro batch culture and human gut model systems, studies were conducted to determine whether increased availability of dietary lipids and/or orlistat affect the composition and/or activity of the faecal microbiota. Results from 24-h batch culture fermentation experiments demonstrated no effect of orlistat in the presence or absence of a dietary lipid (olive oil) on the composition of bacterial communities [as determined by fluorescence in situ hybridization (FISH) and denaturing gradient gel electrophoresis (DGGE) analyses], but did show there was great variability in the lipolytic activities of the microbiotas of individuals, as determined by gas chromatography analysis of long-chain fatty acids in samples. Subsequent studies focused on the effect of orlistat in the presence and absence of lipid in in vitro human gut model systems. Systems were run for 14 days with gut model medium (GMM) only (to steady state, SS), then fed at 12-h intervals with 50 mg orlistat, 2 g olive oil or a mixture of both for 14 days. FISH and DGGE were used to monitor changes in bacterial populations. Bacteria were cultivated from the GMM only (control) systems at SS. All strains isolated were screened for lipolytic activity using tributyrin agar. FISH and DGGE demonstrated that none of the compounds (singly or in combination) added to the systems had any notable effect on microbial population dynamics for any of the donors, although Subdoligranulum populations appeared to be inhibited by orlistat in the presence or absence of lipid. Orlistat had little or no effect on the metabolism of indigenous and added lipids in the fermentation systems, but there was great variability in the way the faecal microbiotas of the donors were able to degrade added lipids. Variability in lipid degradation could be correlated with the number and activity of isolated lipolytic bacteria. The mechanism by which orlistat and the GI microbiota cause side-effects in individuals is unknown, but several hypotheses have been proposed to account for their manifestation. The demonstration of great variability in the lipolytic activity of microbiotas to degrade lipids led to a large-scale cultivation-based study of lipolytic/lipase-positive bacteria present in the human faecal microbiota. Of 4,000 colonies isolated from 15 donors using five different agars, 378 strains were identified that had lipase activity. Molecular identification of strains isolated from five donors demonstrated that lipase activity is more prevalent in the human GI microbiota than previously thought, with members of the phyla Firmicutes, Bacteroidetes and Actinobacteria identified. Molecular identification and characterization of the substrate specificities of the strains will be carried out as part of ongoing work.

Inverse model control using recurrent networks

This paper illustrates how internal model control of nonlinear processes can be achieved by recurrent neural networks, e.g. fully connected Hopfield networks. It is shown that using results developed by Kambhampati et al. (1995), that once a recurrent network model of a nonlinear system has been produced, a controller can be produced which consists of the network comprising the inverse of the model and a filter. Thus, the network providing control for the nonlinear system does not require any training after it has been trained to model the nonlinear system. Stability and other issues of importance for nonlinear control systems are also discussed.

Parallelism in control

A parallel structure is suggested for feedback control systems. Such a technique can be applied to either single or multi-sensor environments and is ideally suited for parallel processor implementation. The control input actually applied is based on a weighted summation of the different parallel controller values, the weightings being either fixed values or chosen by an adaptive decision-making mechanism. The effect of different controller combinations is a field now open to study.

H∞ robust control design for unsupported paraplegic standing: experimental evaluation

This paper is concerned with the design of robust feedback H~-control systems for the control of the upright posture of paraplegic persons standing. While the subject stands in a special apparatus, stabilising torque at the ankle joint is generated by electrical stimulation of the paralyzed calf muscles. Since the muscles acting as actuators in this setup show a significant degree of nonlinearity, a robust H~-control design is used. The design approach is implemented in experiments with a paraplegic subject. The results demonstrate good performance and closed loop stability over the whole range of operation.

Recent developments in intelligent control

Intelligent control, as a discipline, has certainly been one of main growth areas in the field of control systems over the last 5-10 years. Although the topic is relatively new in itself, a number of other research areas, some of them well established, have effectively been swallowed up under the overall intelligent control umbrella. This paper defines intelligent control and identifies the main sub-areas in which significant progress has been made and likely fruitful topics to pursue in the future.

Intelligent agents enabling negotiated control of pervasive environments

One of the important goals of the intelligent buildings especially in commercial applications is not only to minimize the energy consumption but also to enhance the occupant’s comfort. However, most of current development in the intelligent buildings focuses on an implementation of the automatic building control systems that can support energy efficiency approach. The consideration of occupants’ preferences is not adequate. To improve occupant’s wellbeing and energy efficiency in intelligent environments, we develop four types of agent combined together to form a multi-agent system to control the intelligent buildings. Users’ preferential conflicts are discussed. Furthermore, a negotiation mechanism for conflict resolution, has been proposed in order to reach an agreement, and has been represented in syntax directed translation schemes for future implementation and testing. Keywords: conflict resolution, intelligent buildings, multi-agent systems (MAS), negotiation strategy, syntax directed translation schemes (SDTS).

The Mathematics of Control Theory

This text contains papers presented at the Institute of Mathematics and its Applications Conference on Control Theory, held at the University of Strathclyde in Glasgow. The contributions cover a wide range of topics of current interest to theoreticians and practitioners including algebraic systems theory, nonlinear control systems, adaptive control, robustness issues, infinite dimensional systems, applications studies and connections to mathematical aspects of information theory and data-fusion.

A MATLAB GUI for learning controller design in the frequency domain

A MATLAB GUI is presented which is used to help students learn to design controllers in the frequency domain. It complements the author’s two previous GUIs for plotting and identification of systems in the frequency domain. It also incorporates the concept used in the “electronic calculator that makes students think” to assist learning. Positive student feedback affirms that the GUI has helped their understanding.

Regularization of descriptor systems

Implicit dynamic-algebraic equations, known in control theory as descriptor systems, arise naturally in many applications. Such systems may not be regular (often referred to as singular). In that case the equations may not have unique solutions for consistent initial conditions and arbitrary inputs and the system may not be controllable or observable. Many control systems can be regularized by proportional and/or derivative feedback.We present an overview of mathematical theory and numerical techniques for regularizing descriptor systems using feedback controls. The aim is to provide stable numerical techniques for analyzing and constructing regular control and state estimation systems and for ensuring that these systems are robust. State and output feedback designs for regularizing linear time-invariant systems are described, including methods for disturbance decoupling and mixed output problems. Extensions of these techniques to time-varying linear and nonlinear systems are discussed in the final section.