Fractional dynamical model for the generation of ECG like signals from filtered coupled Van-der Pol oscillators

This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this record.In this paper, an incommensurate fractional order (FO) model has been proposed to generate ECG like waveforms. Earlier investigation of ECG like waveform generation is based on two identical Van-der Pol (VdP) family of oscillators, which are coupled by time delays and gains. In this paper, we suitably modify the three state equations corresponding to the nonlinear cross-product of states, time delay coupling of the two oscillators and low-pass filtering, using the concept of fractional derivatives. Our results show that a wide variety of ECG like waveforms can be simulated from the proposed generalized models, characterizing heart conditions under different physiological conditions. Such generalization of the modelling of ECG waveforms may be useful to understand the physiological process behind ECG signal generation in normal and abnormal heart conditions. Along with the proposed FO models, an optimization based approach is also presented to estimate the VdP oscillator parameters for representing a realistic ECG like signal.The work presented in this paper was supported by the E.U. ARTEMIS Joint Undertaking under the Cyclic and Person-Centric Health Management: Integrated appRoach for hOme, mobile and clinical eNvironments – (CHIRON) Project, Grant Agreement # 2009-1-100228

Description of motor control using inverse models

Humans can perform complicated movements like writing or running without giving them much thought. The scientific understanding of principles guiding the generation of these movements is incomplete. How the nervous system ensures stability or compensates for injury and constraints – are among the unanswered questions today. Furthermore, only through movement can a human impose their will and interact with the world around them. Damage to a part of the motor control system can lower a person’s quality of life. Understanding how the central nervous system (CNS) forms control signals and executes them helps with the construction of devices and rehabilitation techniques. This allows the user, at least in part, to bypass the damaged area or replace its function, thereby improving their quality of life. CNS forms motor commands, for example a locomotor velocity or another movement task. These commands are thought to be processed through an internal model of the body to produce patterns of motor unit activity. An example of one such network in the spinal cord is a central pattern generator (CPG) that controls the rhythmic activation of synergistic muscle groups for overground locomotion. The descending drive from the brainstem and sensory feedback pathways initiate and modify the activity of the CPG. The interactions between its inputs and internal dynamics are still under debate in experimental and modelling studies. Even more complex neuromechanical mechanisms are responsible for some non-periodic voluntary movements. Most of the complexity stems from internalization of the body musculoskeletal (MS) system, which is comprised of hundreds of joints and muscles wrapping around each other in a sophisticated manner. Understanding their control signals requires a deep understanding of their dynamics and principles, both of which remain open problems. This dissertation is organized into three research chapters with a bottom-up investigation of motor control, plus an introduction and a discussion chapter. Each of the three research chapters are organized as stand-alone articles either published or in preparation for submission to peer-reviewed journals. Chapter two introduces a description of the MS kinematic variables of a human hand. In an effort to simulate human hand motor control, an algorithm was defined that approximated the moment arms and lengths of 33 musculotendon actuators spanning 18 degrees of freedom. The resulting model could be evaluated within 10 microseconds and required less than 100 KB of memory. The structure of the approximating functions embedded anatomical and functional features of the modelled muscles, providing a meaningful description of the system. The third chapter used the developments in musculotendon modelling to obtain muscle activity profiles controlling hand movements and postures. The agonist-antagonist coactivation mechanism was responsible for producing joint stability for most degrees of freedom, similar to experimental observations. Computed muscle excitations were used in an offline control of a myoelectric prosthesis for a single subject. To investigate the higher-order generation of control signals, the fourth chapter describes an analytical model of CPG. Its parameter space was investigated to produce forward locomotion when controlled with a desired speed. The model parameters were varied to produce asymmetric locomotion, and several control strategies were identified. Throughout the dissertation the balance between analytical, simulation, and phenomenological modelling for the description of simple and complex behavior is a recurrent theme of discussion

Методе за оцену електричне активности глатких мишића

Recording of the smooth stomach muscles' electrical activity can be performed by means of Electrogastrography (EGG), a non-invasive technique for acquisition that can provide valuable information regarding the functionality of the gut. While this method had been introduced for over nine decades, it still did not reach its full potential. The main reason for this is the lack of standardization that subsequently led to the limited reproducibility and comparability between different investigations. Additionally, variability between many proposed recording approaches could make EGG unappealing for broader application. The aim was to provide an evaluation of a simplified recording protocol that could be obtained by using only one bipolar channel for a relatively short duration (20 minutes) in a static environment with limited subject movements. Insights into the most suitable surface electrode placement for EGG recording was also presented. Subsequently, different processing methods, including Fractional Order Calculus and Video-based approach for the cancelation of motion artifacts – one of the main pitfalls in the EGG technique, was examined. For EGG, it is common to apply long-term protocols in a static environment. Our second goal was to introduce and investigate the opposite approach – short-term recording in a dynamic environment. Research in the field of EGG-based assessment of gut activity in relation to motion sickness symptoms induced by Virtual Reality and Driving Simulation was performed. Furthermore, three novel features for the description of EGG signal (Root Mean Square, Median Frequency, and Crest Factor) were proposed and its applicability for the assessment of gastric response during virtual and simulated experiences was evaluated. In conclusion, in a static environment, the EGG protocol can be simplified, and its duration can be reduced. In contrast, in a dynamic environment, it is possible to acquire a reliable EGG signal with appropriate recommendations stated in this Doctoral dissertation. With the application of novel processing techniques and features, EGG could be a useful tool for the assessment of cybersickness and simulator sickness.Снимање електричне активности глатких мишића желуца може се реализовати употребом електрогастрографије (ЕГГ), неинвазивне методе која пружа значајне информације везане за функционисање органа за варење. Упркост чињеници да је откривена пре више од девет деценија, ова техника још увек није остварила свој пун потенцијал. Основни разлог за то је недостатак стандардизације који условљава ограничења у смислу поновљивости и упоредивости између различитих истраживања. Додатно, варијабилност која је присутна у примени различитих препоручених поступака снимања, може смањити интерес за употребу ЕГГ-а код широког опсега потенцијалних корисника. Наш циљ је био да пружимо евалуацију поједностављене методе мерења тј. протокола који укључује само један канал током релативно кратког временског периода (20 минута) у статичким условима са ограниченим кретањем субјекта тј. у мировању. Такође, приказали смо наше ставове у вези најприкладније позиције површинских електрода за ЕГГ снимање. Презентовали смо и резултате испитивања метода, на бази обраде видео снимка као и фракционог диференцијалног рачуна, за отклањање артефаката помераја – једног од највећих изазова са којима је суочена ЕГГ метода. За ЕГГ је уобичајено да се користе дуготрајни протоколи у статичким условима. Наш други циљ био је да представимо и оценимо употребљивост супротног приступа – краткотрајних снимања у динамичким условима. Реализовали смо истраживање на пољу оцене активности желуца током појаве симптома мучнине изазване виртуелном реалношћу и симулацијом вожње. За потребе методе за оцену електричне активности желуца, предложили смо три нова параметра за квантификацију ЕГГ сигнала (ефективну вредност амплитуде, медијану и крест фактор) и извршили процену њихове прикладности за оцену гастроинтестиналног тракта током коришћења виртуелне реалности и симулатора вожње. Закључак је да ЕГГ протокол у статичким условима може бити упрошћен и његово трајање може бити редуковано, док је у динамичким условима могуће снимити одговарајући ЕГГ сигнал, али уз праћење препорука наведених у овој тези. Употребом нових техника за процесирање сигнала и прорачун одговарајућих параметара, ЕГГ може бити корисна техника за оцену мучнине изазване коришћењем симулатора и производа виртуелне реалност

The Role of the Liver Sinusoidal Endothelial Cells in the Pathophysiology of Insulin Resistance

Ageing is associated with increased prevalence of metabolic syndrome, as well as impaired glucose metabolism, hyperinsulinemia and insulin resistance. The mechanism underlying these associations is poorly understood and is likely to be complex and multifactorial. The liver is the key target for insulin action and while the endothelium has been shown to influence insulin activity in muscle and fat, the role of the liver sinusoidal endothelium on the action of insulin in the liver is unknown. The liver sinusoidal endothelium is unique: it is perforated with transcellular pores called fenestrations that facilitate unimpeded passage of substrates between blood and hepatocytes. A constellation of age-related morphological changes in the liver sinusoidal endothelium known as pseudocapillarisation have been described in various species including rats, baboons and humans. During ageing, the liver sinusoidal endothelium thickens, there is basement membrane deposition, and the fenestrations are significantly reduced in size and number (defenestration). Age-related pesudocapillarisation has been shown previously to impede the transfer of lipoproteins and medications across the hepatic sinusoidal endothelium. This thesis tests the hypothesis that changes in the ageing liver contribute to age-related insulin resistance, with alterations of the liver sinusoidal endothelial cell leading to age-related impairment of insulin action and insulin resistance/glucose metabolism. This work aims to improve the understanding of the effects of ageing processes in the liver on insulin action and glucose metabolism. It investigates the role of age-related pseudocapillarisation and the acutely induced poloxamer 407 (P407) model of defenestration in hepatic disposition of insulin and glucose metabolism. This thesis also investigates the effect of P407 on the relationship between membrane rafts and fenestrations in SKHep1 cells, a cell line of liver endothelial origin and isolated LSECs. Finally, the effects of dietary macronutrients and calorie intake on fenestrations in old age are examined. The work contained in this thesis aims to examine the role of age-related pseudocapillarisation in one of the major causes of age-related disease and disability, insulin resistance. In doing so it explores the potential mechanisms involved in these changes and how we may alter the progression of ageing through nutritional intervention

Modelling and characterisation of antennas and propagation for body-centric wireless communication

PhDBody-Centric Wireless Communication (BCWC) is a central point in the development of fourth generation mobile communications. The continuous miniaturisation of sensors, in addition to the advancement in wearable electronics, embedded software, digital signal processing and biomedical technologies, have led to a new concept of usercentric networks, where devices can be carried in the user’s pockets, attached to the user’s body or even implanted. Body-centric wireless networks take their place within the personal area networks, body area networks and body sensor networks which are all emerging technologies that have a broad range of applications such as healthcare and personal entertainment. The major difference between BCWC and conventional wireless systems is the radio channel over which the communication takes place. The human body is a hostile environment from radio propagation perspective and it is therefore important to understand and characterise the effect of the human body on the antenna elements, the radio channel parameters and hence the system performance. This is presented and highlighted in the thesis through a combination of experimental and electromagnetic numerical investigations, with a particular emphasis to the numerical analysis based on the finite-difference time-domain technique. The presented research work encapsulates the characteristics of the narrowband (2.4 GHz) and ultra wide-band (3-10 GHz) on-body radio channels with respect to different digital phantoms, body postures, and antenna types hence highlighting the effect of subject-specific modelling, static and dynamic environments and antenna performance on the overall body-centric network. The investigations covered extend further to include in-body communications where the radio channel for telemetry with medical implants is also analysed by considering the effect of different digital phantoms on the radio channel characteristics. The study supports the significance of developing powerful and reliable numerical modelling to be used in conjunction with measurement campaigns for a comprehensive understanding of the radio channel in body-centric wireless communication. It also emphasises the importance of considering subject-specific electromagnetic modelling to provide a reliable prediction of the network performance

SYSTEMS-LEVEL MODELING AND VALIDATION OF CARDIOVASCULAR SYSTEM RESPONSES TO FLUID AND VASOPRESSOR INFUSION FOR AUTOMATED CRITICAL CARE SYSTEMS

Effective treatment of critically ill patients requires adequate administration of drugs to resuscitate and stabilize the patient by maintaining the volume of blood against bleeding and preserving the blood circulation to the body tissues. In today’s clinical practice, drug dose is adjusted by human clinicians. Therefore, treatment is often subjective and ad-hoc depending on the style and experience of the clinician. Thus, in theory, it is anticipated that well-designed automated critical care systems can help clinicians make superior adjustments to drug doses while they are always vigilant and never distracted by other obligations. Yet, automated critical care systems developed by researchers are ad-hoc, because they determine the control law, i.e., drug infusion rate, using input-output observations rather than the insights on the patient’s physiological states gained from rigorous data-based analysis of mathematical models. Thus, it is worth developing model-based automated systems relating the fluid and vasopressor dose input to the underlying physiological states. This necessitates dose-response mathematical models capable of reproducing realistic physiological and dose-mediated states with reasonable computational load. However, most of existing models are too simplistic to reflect physiological reality, while others are too complicated with thousands of parameters to tune. To address these challenges, we believe that a hybrid physiologic-phenomenological modeling paradigm is effective in developing mathematical models for automated systems: low-order phenomenological models with adaptive personalization capability are suited to develop control algorithms, while physiological models can provide high-fidelity patterns with physiological transparency suited to interpret the underlying physiological states. In this study, hybrid physiologic-phenomenological models of blood volume and cardiovascular responses to fluid and vasopressor infusion are successfully developed and validated using experimental data. It is shown that the models can adequately reproduce the underlying physiological states and endpoints to fluid and vasopressor infusion. The main contributions of this research are lined in the following three folds. First, the models are robust against inter-individual variability, in which they can be adapted to each patient with a small number of tunable parameters. Second, they are physiologically transparent where the underlying physiological states not measured in the standard clinical setting can be interpreted and streamlined during an intervention. And eventually the interpreted underlying states can be employed as direct endpoints to monitor the patient and guide the treatment in a closed-loop or decision-support platform

The sensitivity of the cochlear amplifier to changes in operating conditions

Frequency selectivity is one of the most important functions of the mammalian hearing organ – the cochlea. The interaction of fluid mass and organ of Corti compliance sets a traveling wave along the basilar membrane (BM), which is longitudinally tuned to different frequencies. Beyond this passive tuning process, cochlear amplification locally enhances the vibration of the best frequency peak by factors of hundreds to boost the frequency selectivity and sensitivity of the cochlea. This amplification is achieved by a positive feedback loop between BM motion and outer hair cell (OHC) electrical-mechanical response. However, this active mechanism is vulnerable to damage and cannot be fully recovered in vivo. As the instruments of cochlear amplification, the frequency response of BM and OHCs are of great importance to understand cochlear tuning process. This thesis used animal models, aimed to understand cochlear tuning and investigate possibilities to manipulate the cochlear amplifier, by testing the cochlear amplifier’s sensitivity to operating conditions. The first project tested whether the cochlear amplification can adjust to a lower endocochlear potential (EP), which controls OHC electromechanical force by providing part of the voltage source to drive OHC transduction current. To investigate this possibility, we use intraperitoneal (IP) and intravenous (IV) injection of furosemide to reversibly reduce EP, while monitoring the EP and cochlear amplification simultaneously. Cochlear amplification was monitored by measuring the local cochlear microphonic (LCM) and distortion product emission (DPOAE). With IV injection, the cochlear amplification observed in LCM could attain nearly full or even full recovery with reduced EP. This showed the cochlea has an ability to adjust to diminished operating condition. Furthermore, the cochlear amplifier and EP recovered with different time courses: cochlear amplification just started to recover after the EP was nearly fully recovered and stabilized. Using a Boltzmann model and the 2nd harmonic of the LCM to estimate the mechanoelectric transducer channel operating point, we found that the recovery of cochlear amplification occurred with re-centering of the operating point. The second project studied the physiological and anatomical effects of perfusing the cochlea with a viscous fluid, for better understanding cochlear fluid mechanics. Perilymphatic perfusion was applied with artificial perilymph and viscous sodium hyaluronate (Healon, HA) in four different concentrations. Using compound action potential (CAP) thresholds as an indicator of cochlear condition, our results and analysis indicated that the cochlea can sustain, without a significant CAP threshold shift, up to a 1.5 Pa shear stress. Histology of the cochleae perfused with higher shear stress showed the Reissner's membrane was torn. These data also indicated that the cochlea mechanics remains normal within increased perilymphatic fluid viscosity up to an increase of a factor of 50. Beside these findings, a temporary CAP threshold shift was observed, perhaps due to the presence and then clearance of viscous fluid within the cochlea, or to a temporary position shift of the organ of Corti. The last project was to test the effect of OHC intracellular Cl- concentration on cochlear amplification. Chloride is known to enable the electromotility of the OHC by binding its motor protein, prestin. By locally perfusing high chloride perilymph and the chloride ionophore tributyltin, this study investigated whether increasing intracellular chloride concentration can restore cochlear sensitivity in a cochlea that was slightly damaged. This had been shown by others in guinea pig. However, we did not observe recovery in several attempts in gerbil

Graduate Course Descriptions, 2005 Fall

Wright State University graduate course descriptions from Fall 2005