Non-alcoholic fatty liver disease : can ultrasound assist in early diagnosis of prediabetes and delay progression to type2 diabetes mellitus

Non Alcoholic Fatty Liver Disease (NAFLD) is a condition that is frequently seen but seldom investigated. Until recently, NAFLD was considered benign, self-limiting and unworthy of further investigation. This opinion is based on retrospective studies with relatively small numbers and scant follow-up of histology data. (1) The prevalence for adults, in the USA is, 30%, and NAFLD is recognized as a common and increasing form of liver disease in the paediatric population (1). Australian data, from New South Wales, suggests the prevalence of NAFLD in “healthy” 15 year olds as being 10%.(2) Non-alcoholic fatty liver disease is a condition where fat progressively invades the liver parenchyma. The degree of infiltration ranges from simple steatosis (fat only) to steatohepatitis (fat and inflammation) steatohepatitis plus fibrosis (fat, inflammation and fibrosis) to cirrhosis (replacement of liver texture by scarred, fibrotic and non functioning tissue).Non-alcoholic fatty liver is diagnosed by exclusion rather than inclusion. None of the currently available diagnostic techniques -liver biopsy, liver function tests (LFT) or Imaging; ultrasound, Computerised tomography (CT) or Magnetic Resonance Imaging (MRI) are specific for non-alcoholic fatty liver. An association exists between NAFLD, Non Alcoholic Steatosis Hepatitis (NASH) and irreversible liver damage, cirrhosis and hepatoma. However, a more pervasive aspect of NAFLD is the association with Metabolic Syndrome. This Syndrome is categorised by increased insulin resistance (IR) and NAFLD is thought to be the hepatic representation. Those with NAFLD have an increased risk of death (3) and it is an independent predictor of atherosclerosis and cardiovascular disease (1). Liver biopsy is considered the gold standard for diagnosis, (4), and grading and staging, of non-alcoholic fatty liver disease. Fatty-liver is diagnosed when there is macrovesicular steatosis with displacement of the nucleus to the edge of the cell and at least 5% of the hepatocytes are seen to contain fat (4).Steatosis represents fat accumulation in liver tissue without inflammation. However, it is only called non-alcoholic fatty liver disease when alcohol - >20gms-30gms per day (5), has been excluded from the diet. Both non-alcoholic and alcoholic fatty liver are identical on histology. (4).LFT’s are indicative, not diagnostic. They indicate that a condition may be present but they are unable to diagnosis what the condition is. When a patient presents with raised fasting blood glucose, low HDL (high density lipoprotein), and elevated fasting triacylglycerols they are likely to have NAFLD. (6) Of the imaging techniques MRI is the least variable and the most reproducible. With CT scanning liver fat content can be semi quantitatively estimated. With increasing hepatic steatosis, liver attenuation values decrease by 1.6 Hounsfield units for every milligram of triglyceride deposited per gram of liver tissue (7). Ultrasound permits early detection of fatty liver, often in the preclinical stages before symptoms are present and serum alterations occur. Earlier, accurate reporting of this condition will allow appropriate intervention resulting in better patient health outcomes. References 1. Chalasami N. Does fat alone cause significant liver disease: It remains unclear whether simple steatosis is truly benign. American Gastroenterological Association Perspectives, February/March 2008 www.gastro.org/wmspage.cfm?parm1=5097 Viewed 20th October, 2008 2. Booth, M. George, J.Denney-Wilson, E: The population prevalence of adverse concentrations with adiposity of liver tests among Australian adolescents. Journal of Paediatrics and Child Health.2008 November 3. Catalano, D, Trovato, GM, Martines, GF, Randazzo, M, Tonzuso, A. Bright liver, body composition and insulin resistance changes with nutritional intervention: a follow-up study .Liver Int.2008; February 1280-9 4. Choudhury, J, Sanysl, A. Clinical aspects of Fatty Liver Disease. Semin in Liver Dis. 2004:24 (4):349-62 5. Dionysus Study Group. Drinking factors as cofactors of risk for alcohol induced liver change. Gut. 1997; 41 845-50 6. Preiss, D, Sattar, N. Non-alcoholic fatty liver disease: an overview of prevalence, diagnosis, pathogenesis and treatment considerations. Clin Sci.2008; 115 141-50 7. American Gastroenterological Association. Technical review on nonalcoholic fatty liver disease. Gastroenterology.2002; 123: 1705-25

Delay-dependent robust H-infinity control for uncertain systems with time-varying delay

This paper proposes a new approach for delay-dependent robust H-infinity stability analysis and control synthesis of uncertain systems with time-varying delay. The key features of the approach include the introduction of a new Lyapunov–Krasovskii functional, the construction of an augmented matrix with uncorrelated terms, and the employment of a tighter bounding technique. As a result, significant performance improvement is achieved in system analysis and synthesis without using either free weighting matrices or model transformation. Examples are given to demonstrate the effectiveness of the proposed approach.

New Approach on Robust Delay-Dependent H∞ Control for Uncertain T-S Fuzzy Systems With Interval Time-Varying Delay

This paper investigates the robust H∞ control for Takagi-Sugeno (T-S) fuzzy systems with interval time-varying delay. By employing a new and tighter integral inequality and constructing an appropriate type of Lyapunov functional, delay-dependent stability criteria are derived for the control problem. Because neither any model transformation nor free weighting matrices are employed in our theoretical derivation, the developed stability criteria significantly improve and simplify the existing stability conditions. Also, the maximum allowable upper delay bound and controller feedback gains can be obtained simultaneously from the developed approach by solving a constrained convex optimization problem. Numerical examples are given to demonstrate the effectiveness of the proposed methods.

Delay distribution based robust H∞ control of networked control systems with uncertainties

Network induced delay in networked control systems (NCS) is inherently non-uniformly distributed and behaves with multifractal nature. However, such network characteristics have not been well considered in NCS analysis and synthesis. Making use of the information of the statistical distribution of NCS network induced delay, a delay distribution based stochastic model is adopted to link Quality-of-Control and network Quality-of-Service for NCS with uncertainties. From this model together with a tighter bounding technology for cross terms, H∞ NCS analysis is carried out with significantly improved stability results. Furthermore, a memoryless H∞ controller is designed to stabilize the NCS and to achieve the prescribed disturbance attenuation level. Numerical examples are given to demonstrate the effectiveness of the proposed method.

FPGA implementation of dual-microphone delay-and-sum beamforming for in-car speech enhancement and recognition

In an automotive environment, the performance of a speech recognition system is affected by environmental noise if the speech signal is acquired directly from a microphone. Speech enhancement techniques are therefore necessary to improve the speech recognition performance. In this paper, a field-programmable gate array (FPGA) implementation of dual-microphone delay-and-sum beamforming (DASB) for speech enhancement is presented. As the first step towards a cost-effective solution, the implementation described in this paper uses a relatively high-end FPGA device to facilitate the verification of various design strategies and parameters. Experimental results show that the proposed design can produce output waveforms close to those generated by a theoretical (floating-point) model with modest usage of FPGA resources. Speech recognition experiments are also conducted on enhanced in-car speech waveforms produced by the FPGA in order to compare recognition performance with the floating-point representation running on a PC.

Generalized binomial Tau-leap method for biochemical kinetics incorporating both delay and intrinsic noise

The delay stochastic simulation algorithm (DSSA) by Barrio et al. [Plos Comput. Biol.2, 117–E (2006)] was developed to simulate delayed processes in cell biology in the presence of intrinsic noise, that is, when there are small-to-moderate numbers of certain key molecules present in a chemical reaction system. These delayed processes can faithfully represent complex interactions and mechanisms that imply a number of spatiotemporal processes often not explicitly modeled such as transcription and translation, basic in the modeling of cell signaling pathways. However, for systems with widely varying reaction rate constants or large numbers of molecules, the simulation time steps of both the stochastic simulation algorithm (SSA) and the DSSA can become very small causing considerable computational overheads. In order to overcome the limit of small step sizes, various τ-leap strategies have been suggested for improving computational performance of the SSA. In this paper, we present a binomial τ- DSSA method that extends the τ-leap idea to the delay setting and avoids drawing insufficient numbers of reactions, a common shortcoming of existing binomial τ-leap methods that becomes evident when dealing with complex chemical interactions. The resulting inaccuracies are most evident in the delayed case, even when considering reaction products as potential reactants within the same time step in which they are produced. Moreover, we extend the framework to account for multicellular systems with different degrees of intercellular communication. We apply these ideas to two important genetic regulatory models, namely, the hes1 gene, implicated as a molecular clock, and a Her1/Her 7 model for coupled oscillating cells.

Oscillatory regulation of Hes1: Discrete stochastic delay modelling and simulation

Discrete stochastic simulations are a powerful tool for understanding the dynamics of chemical kinetics when there are small-to-moderate numbers of certain molecular species. In this paper we introduce delays into the stochastic simulation algorithm, thus mimicking delays associated with transcription and translation. We then show that this process may well explain more faithfully than continuous deterministic models the observed sustained oscillations in expression levels of hes1 mRNA and Hes1 protein.

A transport protocol for real-time applications in wireless networked control systems

A Networked Control System (NCS) is a feedback-driven control system wherein the control loops are closed through a real-time network. Control and feedback signals in an NCS are exchanged among the system’s components in the form of information packets via the network. Nowadays, wireless technologies such as IEEE802.11 are being introduced to modern NCSs as they offer better scalability, larger bandwidth and lower costs. However, this type of network is not designed for NCSs because it introduces a large amount of dropped data, and unpredictable and long transmission latencies due to the characteristics of wireless channels, which are not acceptable for real-time control systems. Real-time control is a class of time-critical application which requires lossless data transmission, small and deterministic delays and jitter. For a real-time control system, network-introduced problems may degrade the system’s performance significantly or even cause system instability. It is therefore important to develop solutions to satisfy real-time requirements in terms of delays, jitter and data losses, and guarantee high levels of performance for time-critical communications in Wireless Networked Control Systems (WNCSs). To improve or even guarantee real-time performance in wireless control systems, this thesis presents several network layout strategies and a new transport layer protocol. Firstly, real-time performances in regard to data transmission delays and reliability of IEEE 802.11b-based UDP/IP NCSs are evaluated through simulations. After analysis of the simulation results, some network layout strategies are presented to achieve relatively small and deterministic network-introduced latencies and reduce data loss rates. These are effective in providing better network performance without performance degradation of other services. After the investigation into the layout strategies, the thesis presents a new transport protocol which is more effcient than UDP and TCP for guaranteeing reliable and time-critical communications in WNCSs. From the networking perspective, introducing appropriate communication schemes, modifying existing network protocols and devising new protocols, have been the most effective and popular ways to improve or even guarantee real-time performance to a certain extent. Most previously proposed schemes and protocols were designed for real-time multimedia communication and they are not suitable for real-time control systems. Therefore, devising a new network protocol that is able to satisfy real-time requirements in WNCSs is the main objective of this research project. The Conditional Retransmission Enabled Transport Protocol (CRETP) is a new network protocol presented in this thesis. Retransmitting unacknowledged data packets is effective in compensating for data losses. However, every data packet in realtime control systems has a deadline and data is assumed invalid or even harmful when its deadline expires. CRETP performs data retransmission only in the case that data is still valid, which guarantees data timeliness and saves memory and network resources. A trade-off between delivery reliability, transmission latency and network resources can be achieved by the conditional retransmission mechanism. Evaluation of protocol performance was conducted through extensive simulations. Comparative studies between CRETP, UDP and TCP were also performed. These results showed that CRETP significantly: 1). improved reliability of communication, 2). guaranteed validity of received data, 3). reduced transmission latency to an acceptable value, and 4). made delays relatively deterministic and predictable. Furthermore, CRETP achieved the best overall performance in comparative studies which makes it the most suitable transport protocol among the three for real-time communications in a WNCS.