Signal Processing Using Non-invasive Physiological Sensors

Non-invasive biomedical sensors for monitoring physiological parameters from the human body for potential future therapies and healthcare solutions. Today, a critical factor in providing a cost-effective healthcare system is improving patients' quality of life and mobility, which can be achieved by developing non-invasive sensor systems, which can then be deployed in point of care, used at home or integrated into wearable devices for long-term data collection. Another factor that plays an integral part in a cost-effective healthcare system is the signal processing of the data recorded with non-invasive biomedical sensors. In this book, we aimed to attract researchers who are interested in the application of signal processing methods to different biomedical signals, such as an electroencephalogram (EEG), electromyogram (EMG), functional near-infrared spectroscopy (fNIRS), electrocardiogram (ECG), galvanic skin response, pulse oximetry, photoplethysmogram (PPG), etc. We encouraged new signal processing methods or the use of existing signal processing methods for its novel application in physiological signals to help healthcare providers make better decisions

An assesment of the accuracy and role of self-recorded blood pressures in the managment of hypertension

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Novel concepts for non-invasive telemonitoring in chronic heart failure

Background: The morbidity and mortality from chronic heart failure (HF) remains alarmingly high, in part due to failure to apply substantial disease modifying strategies to halt disease progression. Telemonitoring has been proposed as a potential disease management strategy to deal with the burden posed by HF. While treatment decisions guided by invasive telemonitoring data have shown early promise, it is unclear whether non-invasively derived surrogates of haemodynamics could be reliable enough to guide therapeutic interventions.Aims: The principal aim of this thesis is to investigate whether non-invasive “smart technologies” could accurately detect and track subtle changes in surrogates of cardiovascular haemodynamics in response to challenges posed by activities of daily living and non-adherence to therapy. Methodology: A series of prospective clinical studies were conducted in stable patients with chronic heart failure, on optimum tolerated guideline directed therapy for heart failure. Studies were performed under clinically adapted conditions to mimic the patient’s own habitat.Results: Significant systemic haemodynamic perturbations were detected non-invasively with variations in environmental temperature. Additionally, music, which modulates the sympathetic tone, led to modest changes in systemic blood pressure and heart rate, although the changes did not reach statistical significance. Non-adherence to cardiovascular therapy led to striking adverse changes in systemic haemodynamics. Smart technologies demonstrated a remarkable consistency in detecting haemodynamic perturbations.Conclusion: Non-invasive detection and tracking of changes in haemodynamics is feasible with smart technologies. The results need to be validated in larger multicenter clinical trials, with particular emphasis on using the data to guide therapeutic decisions

On the Recognition of Emotion from Physiological Data

This work encompasses several objectives, but is primarily concerned with an experiment where 33 participants were shown 32 slides in order to create ‗weakly induced emotions‘. Recordings of the participants‘ physiological state were taken as well as a self report of their emotional state. We then used an assortment of classifiers to predict emotional state from the recorded physiological signals, a process known as Physiological Pattern Recognition (PPR). We investigated techniques for recording, processing and extracting features from six different physiological signals: Electrocardiogram (ECG), Blood Volume Pulse (BVP), Galvanic Skin Response (GSR), Electromyography (EMG), for the corrugator muscle, skin temperature for the finger and respiratory rate. Improvements to the state of PPR emotion detection were made by allowing for 9 different weakly induced emotional states to be detected at nearly 65% accuracy. This is an improvement in the number of states readily detectable. The work presents many investigations into numerical feature extraction from physiological signals and has a chapter dedicated to collating and trialing facial electromyography techniques. There is also a hardware device we created to collect participant self reported emotional states which showed several improvements to experimental procedure

Southwest Research Institute assistance to NASA in biomedical areas of the technology

Significant applications of aerospace technology were achieved. These applications include: a miniaturized, noninvasive system to telemeter electrocardiographic signals of heart transplant patients during their recuperative period as graded situations are introduced; and economical vital signs monitor for use in nursing homes and rehabilitation hospitals to indicate the onset of respiratory arrest; an implantable telemetry system to indicate the onset of the rejection phenomenon in animals undergoing cardiac transplants; an exceptionally accurate current proportional temperature controller for pollution studies; an automatic, atraumatic blood pressure measurement device; materials for protecting burned areas in contact with joint bender splints; a detector to signal the passage of animals by a given point during ecology studies; and special cushioning for use with below-knee amputees to protect the integrity of the skin at the stump/prosthesis interface

Multidisciplinary Experiences in Renal Replacement Therapy

Renal replacement therapy (RRT) is used to replace the capacity of blood filtration, which is completely lost in end-stage renal disease (ESRD). This book examines RRT from a multidisciplinary perspective. In nine comprehensive chapters over three sections, the book shows how clinical routines, especially RRT, are increasingly focused on the translational scenario of the health sciences. Chapters discuss health and wellness, hemodialysis, and clinical biomarkers of renal disease

Developing a Lupus Nephritis urinary biomarker panel in children for use in a clinical trial

Background: Juvenile-onset systemic lupus erythematosus (JSLE) is a rare, severe multisystem autoimmune disease affecting the kidney (Lupus Nephritis, LN) in up to 80% of children. Numerous individual urinary biomarkers have previously been investigated. No individual biomarker has achieved ‘excellence’ in differentiating active from inactive LN. Aims: (1) To assess performance of traditional clinical biomarkers for LN monitoring and prediction of LN outcomes. (2) To select biomarkers warranting assessment in a ‘LN biomarker panel’; to cross-sectionally assess if combining novel/traditional biomarkers improves active LN identification. (3) To validate the optimal UK LN biomarkers within independent, ethnically distinct JSLE cohorts. (4) To longitudinally assess if urine biomarkers predict LN flare/remission. (5) To streamline methods for LN urine biomarker panel quantification. Methods: Clinical data and urine samples from UK, United States (US) and South African (SA) JSLE patients were utilised within cross-sectional and longitudinal studies assessing combinations of novel urine/traditional clinical biomarkers. A custom LN biomarker panel multiplex assay was developed/validated in collaboration with Merck Millipore. Results: 37% of UK patients displayed active LN as an initial presenting feature, with a further 17% developing LN after a median of 2.04 years [IQR 0.8-3.7]. ACR score (>5) and C3 levels (<0.9g/L) at baseline were significant predictors of subsequent LN development. 39% of patients recovered from proteinuria following an LN flare during the study period, within a median of 17 months (IQR 4-49) with the remaining 61% continuing to have proteinuria after a median of 22 months (IQR 12-41). Younger patients (<14 yrs), those with a lower eGFR (<80mls/min) and haematological involvement at LN onset, displayed a longer time to proteinuria recovery. ESR, C3, WCC, neutrophils, lymphocytes and IgG contributed significantly to an optimal non-renal traditional biomarker model for active LN identification (AUC 0.72). Novel urine biomarkers were selected for assessment by detailed literature review. Cross-sectional fitting a binary logistic regression models with data from 61 UK patients, the optimal biomarker combination included AGP+CP+LPGDS+TF (AUC 0.920). Inclusion of traditional biomarkers within the model did not improve the AUC further. The novel biomarker panel displayed equivalent ability for identifying active LN in 30 US and 23 SA patients (AUC of 0.991 and 1.00 respectively). Within the longitudinal study, including 244 observations from 80 UK/US/SA patients, a Markov Multi-State model identified AGP to be predictive flare, and CP of remission (model AIC =135). By entering individual AGP/CP patient values into the model, 3, 6, 9 and 12 month probabilities of disease state transition are provided. The multiplex assay demonstrated acceptable cross reactivity between multiplexed antibodies, satisfactory spike recovery, intra/inter-assay precision. Linearity of dilution was unacceptable, therefore rigorous range finding in 106 UK/US/SA samples identified the optimal dilutions required for each biomarker. Combining multiplex biomarker values for AGP+CP+LPGDS+TF within a binary logistic regression model, equivalent ability for identification of active LN was seen (multiplex AUC = 0.998, ELISA AUC = 0.952). Conclusions: This thesis has demonstrated and validated an ‘excellent’ urinary biomarker panel for active LN identification in three ethnically distinct JSLE cohorts. Different constituents of the biomarker panel are best at predicting LN flare/remission. A custom urine biomarker panel multiplex assay has been developed, demonstrating improved ability for active LN identification over existing ELISAs. Future clinical studies prospectively measuring the urine biomarker panel by multiplex are warranted, facilitating refinement of the Markov Multi-State Model and assessing if biomarker-led monitoring can actually improve renal outcomes for children with LN

Investigating the effect of endurance exercise on mitochondrial function in the ageing heart

PhD ThesisMitochondria are organelles present in most cells of the body responsible for the production of cellular energy in the form of adenosine triphosphate (ATP), through oxidative phosphorylation (OXPHOS). Mitochondrial function is particularly important in the heart due to its high requirement for ATP, and a decline in mitochondrial function with age is implicated in the pathogenesis of age-related cardiovascular disease. Exercise interventions can induce mitochondrial biogenesis and increase OXPHOS capacity; however, it is unknown whether such interventions are successful if started in later life. I wanted to investigate the effect of an endurance exercise intervention in 2 mouse models; 1) a model of accelerated ageing due to enhanced mitochondrial DNA mutagenesis (PolgAmut/mutmice); 2) C57Bl6/J mouse model of physiological age at 14 months of age. Study 1: Following baseline characterisation of PolgAmut/mutmice compared with age-matched controls, male PolgAmut/mutmice underwent a 6-month endurance exercise programme from 16 weeks of age to investigate the effects of exercise on physiological phenotype, behavioural activity, and cardiac mitochondrial function. I found no improvement in clinical score, locomotor activity, cardiac hypertrophy and fibrosis and mitochondrial function in the exercised mice. This suggests that six months of endurance exercise is unable to improve the clinical phenotype and cardiac mitochondrial function in PolgAmut/mutmice due to the severity of the genetic defect. Study 2: To investigate whether starting an exercise programme in later life is beneficial, I first characterised the effect of age on cardiac function in sedentary mice. Between 14 and 22 months of age, I found a significant decline in neuromuscular coordination, decreased cardiac function (measured by cardiac MRI), and diminished aerobic capacity. Six months of endurance exercise improved physiological function and neuromuscular coordination, decreased cardiac fibrosis and apoptosis and improved mitochondrial OXPHOS activity. This suggests that starting an exercise programme later in life can still have beneficial effects.The MRG, CAV and Barbour foundatio