Biomedical subjects

Nigel H Lovell

Publications and source records attributed to Nigel H Lovell.

18 recordsLinked to original sources

PubMed2026

Comprehensive evaluation of ACMG/AMP-based variant classification tools.

MOTIVATION: The American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) guidelines represent the gold standard for clinical variant interpretation. Despite the widespread adoption of ACMG/AMP guidelines, a comprehensive comparison of the software tools designed to implement them has been lacking. This represents a significant gap, as clinicians require evidence-based guidance on which tools to use in their practice. RESULTS: We benchmarked four ACMG/AMP-based tools (Franklin, InterVar, TAPES, Genebe) selected from 22 tools, and compared their performance with LIRICAL, a top-performing phenotype-driven tool, using 151 expert-curated datasets from Mendelian disorders. Selection criteria included free availability, VCF compatibility, operational reliability, and not being disease-specific. Our evaluation framework assessed top-N accuracy (N = 1, 5, 10, 20, 50), retention rates, precision, recall, F1 scores, and area under the curve (AUC). Statistical validation employed bootstrap confidence intervals (n = 1000) and Friedman tests. LIRICAL (68.21%) and Franklin (61.59%) demonstrated superior top-10 variant prioritization accuracy in Mendelian disorders, significantly outperforming other tools (P = .0000). Results demonstrate that tools with advanced phenotypic integration significantly outperform those relying primarily on genomic features. AVAILABILITY AND IMPLEMENTATION: All data and source code required to reproduce the findings of this study are openly available in the Code Ocean repository at https://doi.org/10.24433/CO.6562438.v1.

Software↗

PubMed2007

Noninvasive average flow estimation for an implantable rotary blood pump: a new algorithm incorporating the role of blood viscosity.

The effect of blood hematocrit (HCT) on a noninvasive flow estimation algorithm was examined in a centrifugal implantable rotary blood pump (iRBP) used for ventricular assistance. An average flow estimator, based on three parameters, input electrical power, pump speed, and HCT, was developed. Data were collected in a mock loop under steady flow conditions for a variety of pump operating points and for various HCT levels. Analysis was performed using three-dimensional polynomial surfaces to fit the collected data for each different HCT level. The polynomial coefficients of the surfaces were then analyzed as a function of HCT. Linear correlations between estimated and measured pump flow over a flow range from 1.0 to 7.5 L/min resulted in a slope of 1.024 L/min (R2=0.9805). Early patient data tested against the estimator have shown promising consistency, suggesting that consideration of HCT can improve the accuracy of existing flow estimation algorithms.

Algorithms↗

PubMed2006

Classification of a known sequence of motions and postures from accelerometry data using adapted Gaussian mixture models.

Accelerometry shows promise in providing an inexpensive but effective means of long-term ambulatory monitoring of elderly patients. The accurate classification of everyday movements should allow such a monitoring system to exhibit greater 'intelligence', improving its ability to detect and predict falls by forming a more specific picture of the activities of a person and thereby allowing more accurate tracking of the health parameters associated with those activities. With this in mind, this study aims to develop more robust and effective methods for the classification of postures and motions from data obtained using a single, waist-mounted, triaxial accelerometer; in particular, aiming to improve the flexibility and generality of the monitoring system, making it better able to detect and identify short-duration movements and more adaptable to a specific person or device. Two movement classification methods were investigated: a rule-based Heuristic system and a Gaussian mixture model (GMM)-based system. A novel time-domain feature extraction method is proposed for the GMM system to allow better detection of short-duration movements. A method for adapting the GMMs to compensate for the problem of limited user-specific training data is also proposed and investigated. Classification performance was considered in relation to data gathered in an unsupervised, directed routine conducted in a three-month field trial involving six elderly subjects. The GMM system was found to achieve a mean accuracy of 91.3%, distinguishing between three postures (sitting, standing and lying) and five movements (sit-to-stand, stand-to-sit, lie-to-stand, stand-to-lie and walking), compared to 71.1% achieved by the Heuristic system. The adaptation method was found to offer a mean accuracy of 92.2%; a relative improvement of 20.2% over tests without subject-specific data and 4.5% over tests using only a limited amount of subject-specific data. While limited to a restricted subset of possible motions and postures, these results provide a significant step in the search for a more robust and accurate ambulatory classification system.

Acceleration↗

PubMed2006

A comparison of 1-D models of cardiac pacemaker heterogeneity.

In this paper, we investigate the role of sinoatrial node (SAN) cellular heterogeneity in two key aspects of normal cardiac pacemaker function: frequency entrainment of the SAN, and propagation of excitation into the atrial tissue. Using detailed ionic models of electrical activity in SAN and atrial myocytes, we have formulated a number of one-dimensional models of SAN heterogeneity based on discrete-region (in which central and peripheral SAN type cell are separated into discrete regions), gradient and mosaic models of SAN organization. Each of the different models were assessed on their ability to achieve frequency entrainment of the SAN and activation of the adjoining atrial tissue in the presence of both uniform and linearly increasing conductivity profiles. Simulation results suggest that the gradient model of SAN heterogeneity, in which cells display a smooth variation in membrane properties from the center to the periphery of the SAN, produces action potential waveshapes and a site of earliest activation consistent with experimental observations in the intact SAN. The gradient model also achieves frequency entrainment of the SAN more easily than other models of SAN heterogeneity. Based on these results, we conclude that the gradient model of SAN heterogeneity, in the presence of a uniform conductivity profile, is the most likely model of SAN organization.

Action Potentials↗

PubMed2006

Implementation of a real-time human movement classifier using a triaxial accelerometer for ambulatory monitoring.

The real-time monitoring of human movement can provide valuable information regarding an individual's degree of functional ability and general level of activity. This paper presents the implementation of a real-time classification system for the types of human movement associated with the data acquired from a single, waist-mounted triaxial accelerometer unit. The major advance proposed by the system is to perform the vast majority of signal processing onboard the wearable unit using embedded intelligence. In this way, the system distinguishes between periods of activity and rest, recognizes the postural orientation of the wearer, detects events such as walking and falls, and provides an estimation of metabolic energy expenditure. A laboratory-based trial involving six subjects was undertaken, with results indicating an overall accuracy of 90.8% across a series of 12 tasks (283 tests) involving a variety of movements related to normal daily activities. Distinction between activity and rest was performed without error; recognition of postural orientation was carried out with 94.1% accuracy, classification of walking was achieved with less certainty (83.3% accuracy), and detection of possible falls was made with 95.6% accuracy. Results demonstrate the feasibility of implementing an accelerometry-based, real-time movement classifier using embedded intelligence.

Acceleration↗

PubMed2006

Identification and classification of physiologically significant pumping states in an implantable rotary blood pump.

In a clinical setting it is necessary to control the speed of rotary blood pumps used as left ventricular assist devices to prevent possible severe complications associated with over- or underpumping. The hypothesis is that by using only the noninvasive measure of instantaneous pump impeller speed to assess flow dynamics, it is possible to detect physiologically significant pumping states (without the need for additional implantable sensors). By varying pump speed in an animal model, five such states were identified: regurgitant pump flow, ventricular ejection (VE), nonopening of the aortic valve over the cardiac cycle (ANO), and partial collapse (intermittent and continuous) of the ventricle wall (PVC-I and PVC-C). These states are described in detail and a strategy for their noninvasive detection has been developed and validated using (n = 6) ex vivo porcine experiments. Employing a classification and regression tree, the strategy was able to detect pumping states with a high degree of sensitivity and specificity: state VE-99.2/100.0% (sensitivity/specificity); state ANO-100.0/100.0%; state PVC-I- 95.7/91.2%; state PVC-C-69.7/98.7%. With a simplified binary scheme differentiating suction (PVC-I, PVC-C) and nonsuction (VE, ANO) states, both such states were detected with 100% sensitivity.

Algorithms↗

PubMed2005

Architecture for knowledge-based and federated search of online clinical evidence.

BACKGROUND: It is increasingly difficult for clinicians to keep up-to-date with the rapidly growing biomedical literature. Online evidence retrieval methods are now seen as a core tool to support evidence-based health practice. However, standard search engine technology is not designed to manage the many different types of evidence sources that are available or to handle the very different information needs of various clinical groups, who often work in widely different settings. OBJECTIVES: The objectives of this paper are (1) to describe the design considerations and system architecture of a wrapper-mediator approach to federate search system design, including the use of knowledge-based, meta-search filters, and (2) to analyze the implications of system design choices on performance measurements. METHODS: A trial was performed to evaluate the technical performance of a federated evidence retrieval system, which provided access to eight distinct online resources, including e-journals, PubMed, and electronic guidelines. The Quick Clinical system architecture utilized a universal query language to reformulate queries internally and utilized meta-search filters to optimize search strategies across resources. We recruited 227 family physicians from across Australia who used the system to retrieve evidence in a routine clinical setting over a 4-week period. The total search time for a query was recorded, along with the duration of individual queries sent to different online resources. RESULTS: Clinicians performed 1662 searches over the trial. The average search duration was 4.9 +/- 3.2 s (N = 1662 searches). Mean search duration to the individual sources was between 0.05 s and 4.55 s. Average system time (ie, system overhead) was 0.12 s. CONCLUSIONS: The relatively small system overhead compared to the average time it takes to perform a search for an individual source shows that the system achieves a good trade-off between performance and reliability. Furthermore, despite the additional effort required to incorporate the capabilities of each individual source (to improve the quality of search results), system maintenance requires only a small additional overhead.

Decision Making, Computer-Assisted↗

PubMed2005

Simulated prosthetic visual fixation, saccade, and smooth pursuit.

A visual tracking task was administered to 20 subjects afforded simulated prosthetic vision (a phosphene array); a total of 3h data was taken from each subject over the course of 10 visits. The experiment assessed prosthetic visual fixation, saccade and smooth pursuit and the effect of practice. Further, we demonstrated an image analysis technique that assisted fixation and pursuit (but not saccade) accuracy, and required less vigorous movement of the phosphene array in pursuing the target. As measured by mean deviation from the target, fixation and pursuit accuracies were improved by 8.3 and 3.3 min of visual arc, respectively (35.8% and 6.8%), for inter-phosphene spacing of 1.9 degrees . The analysis technique, involving overlapping Gaussian kernels, was an heuristic design; this is the first step of an iterative, experimental approach to devising effective image analysis to be contained in an electronic vision prosthesis. The approach should ultimately afford implanted patients improved prosthetic visual function.

Analysis of Variance↗

PubMed2005

Designing home telecare: a case study in monitoring cystic fibrosis.

The objective of this study was to investigate the feasibility of using home telecare for monitoring cystic fibrosis (CF). Five adolescents were asked to use a home telecare system during a routine hospital visit over one week. Frequency of use was measured from computer logs. Unacceptable measurements were identified by visual inspection. User impressions of home telecare and appropriateness of the system for managing CF was determined from observations of user interaction, survey and qualitative analysis. Patients used the system to record lung function measurements without any supervision and indicated that the system was easy to learn and use. The role of home telecare in supporting collaborative self-management appeared to be well understood. Home telecare was seen as a supplement to standard care that would provide a link to the hospital between clinic visits. Participants indicated that feedback provided by the system and ongoing clinical support would determine long-term use and compliance with the monitoring protocol. Clinicians reported the usefulness of home telecare in maintaining a longitudinal record of their patient's health that would supplement verbal description of symptoms and reduce time to treatment by increasing patient self-awareness of health status. Home telecare may be a feasible intervention for monitoring CF. Feedback provided by the system must be presented in a format that is familiar and easily understood by users. Further system refinement and evaluation is required to determine patient compliance with their customized monitoring protocol prior to assessing impact on clinical outcomes.

Adolescent↗

PubMed2005

A bidomain model of epiretinal stimulation.

A computational bidomain model of epiretinal stimulation is presented, consisting of a continuum description of active retinal tissue in contact with bulk vitreous fluid. Results from two-electrode and four-electrode bipolar stimulation suggest that a biphasic cathodic-anodic stimulus sequence is effective in providing targeted focal activation of retinal tissue. Undesired secondary activations beneath each electrode return may be eliminated by using multiple returns for each stimulus electrode.

Action Potentials↗

PubMed2005

Learning prosthetic vision: a virtual-reality study.

Acceptance of prosthetic vision will be heavily dependent on the ability of recipients to form useful information from such vision. Training strategies to accelerate learning and maximize visual comprehension would need to be designed in the light of the factors affecting human learning under prosthetic vision. Some of these potential factors were examined in a visual acuity study using the Landolt C optotype under virtual-reality simulation of prosthetic vision. Fifteen normally sighted subjects were tested for 10-20 sessions. Potential learning factors were tested at p < 0.05 with regression models. Learning was most evident across-sessions, though 17% of sessions did express significant within-session trends. Learning was highly concentrated toward a critical range of optotype sizes, and subjects were less capable in identifying the closed optotype (a Landolt C with no gap, forming a closed annulus). Training for implant recipients should target these critical sizes and the closed optotype to extend the limit of visual comprehension. Although there was no evidence that image processing affected overall learning, subjects showed varying personal preferences.

Adolescent↗

PubMed2004

Accelerometry: providing an integrated, practical method for long-term, ambulatory monitoring of human movement.

Accelerometry offers a practical and low cost method of objectively monitoring human movements, and has particular applicability to the monitoring of free-living subjects. Accelerometers have been used to monitor a range of different movements, including gait, sit-to-stand transfers, postural sway and falls. They have also been used to measure physical activity levels and to identify and classify movements performed by subjects. This paper reviews the use of accelerometer-based systems in each of these areas. The scope and applicability of such systems in unsupervised monitoring of human movement are considered. The different systems and monitoring techniques can be integrated to provide a more comprehensive system that is suitable for measuring a range of different parameters in an unsupervised monitoring context with free-living subjects. An integrated approach is described in which a single, waist-mounted accelerometry system is used to monitor a range of different parameters of human movement in an unsupervised setting.

Gait↗

PubMed2004

A pilot study of long-term monitoring of human movements in the home using accelerometry.

We assessed the feasibility of using a waist-mounted, wireless triaxial accelerometer (TA) to monitor human movements in an unsupervised home setting to detect changes in functional status. A pilot study was carried out with six healthy subjects aged 80-86 years. The subjects wore a TA unit every day for two to three months. Each morning they carried out a short routine of directed movements that included standing, sitting, lying and walking. Important movement variables were measured. During the rest of the day, subjects were monitored for falls, and variables such as metabolic energy expenditure were measured. All subjects remained healthy; there was no overall change in functional status and there were only slight fluctuations in health status. No longitudinal changes were detected in any of the variables measured during the directed routine. There was a moderate correlation between weekly self-reported health status and energy expenditure: subjects reported a lower health status for weeks in which they expended less energy. The TA system was found to be practical for long-term, unsupervised home monitoring. All subjects found the system simple to use and the TA unit unobtrusive and comfortable to wear. High compliance rates were achieved: the TA units were worn on 88% of the days in the study, for an average of 11.2 hours per day.

Acceleration↗

PubMed2003

Using information technology to improve the management of chronic disease.

Information and communications technology (ICT) is increasingly being used in management of chronic illness to facilitate shared services (virtual health networks and electronic health records), knowledge management (care rules and protocols, scheduling, information directories), as well as consumer-based health education and evidence-based clinical protocols. Common applications of ICT include home monitoring of vital signs for patients with chronic disease, as well as replacing home visits by nurses in person with telemedicine videophone consultations. A patient-managed Home Telecare System with integrated clinical signs monitoring, automated scheduling and medication reminders, as well as access to health education and daily logs, is presented as an example of ICT use for chronic disease self-management. A clinical case study demonstrates how early identification of adverse trends in clinical signs recorded in the home can either avoid hospital readmission or reduce the length of hospital stay.

Australia↗

PubMed2002

Development and surgical implantation of a vision prosthesis model into the ovine eye.

PURPOSE: A surgical technique was designed and tested to enable the implantation of an intraocular electrical retinal stimulator. METHOD: An inoperative perspex and silicone model was constructed to closely resemble the anticipated properties of the proposed visual prosthesis. The animal model chosen for these experiments was the sheep, because the dimensions of its ocular anatomy are approximately 30% larger than the human's, being otherwise grossly similar. The surgical method involved transplanar port-hole lensectomy and vitrectomy, insertion of the model implant through a limbal incision, and fixation of the perspex subunit close to the location of the native crystalline lens, by way of trans-pars plana fixation sutures. Adequate pre-retinal positioning of the implant's silicone extension was obtained by way of its inherent elastic recoil. RESULTS: The procedure was performed without macroscopic evidence of undue surgical trauma. CONCLUSION: Although further long-term experiments are required to fully assess the surgical procedure and biocompatibility of the implant, intraoperative assessment and postmortem computed tomographic imaging of the globe has confirmed the successful intraocular positioning and fixation of the implant.

Animals↗

PubMedDate not supplied

A gradient model of cardiac pacemaker myocytes.

We have formulated a spatial-gradient model of action potential heterogeneity within the rabbit sinoatrial node (SAN), based on cell-specific ionic models of electrical activity from its central and peripheral regions. The ionic models are derived from a generic cell model, incorporating five background and exchange currents, and seven time-dependent currents based on three- or four-state Markov schemes. State transition rates are given by non-linear sigmoid functions of membrane potential. By appropriate selection of parameters, the generic model is able to accurately reproduce a wide range of action potential waveforms observed experimentally. Specifically, the model can fit recordings from central and peripheral regions of the SAN with RMS errors of 0.3987 and 0.7628 m V, respectively. Using a custom least squares parameter optimisation routine, we have constructed a spatially-varying gradient model that exhibits a smooth transition in action potential characteristics from the central to the peripheral region, whilst ensuring individual membrane currents remain physiologically accurate. Smooth transition action potential characteristics include maximum diastolic potential, overshoot potential, upstroke velocity, action potential duration and cycle length. The gradient model is suitable for developing higher dimensional models of the right atrium, in which action potential heterogeneity within nodal tissue may be readily incorporated.

Action Potentials↗

PubMedDate not supplied

Parameter estimation in cardiac ionic models.

We examine the problem of parameter estimation in mathematical models of excitable cell cardiac electrical activity using the well-known Beeler-Reuter (1977) ionic equations for the ventricular action potential. The estimation problem can be regarded as equivalent to the accurate reconstruction of ionic current kinetics and amplitudes in an excitable cell model, given only action potential experimental data. We show that in the Beeler-Reuter case, all ionic currents may be reasonably reconstructed using an experimental design consisting of action potential recordings perturbed by pseudo-random injection currents. The Beeler-Reuter model was parameterised into 63 parameters completely defining all membrane current amplitudes and kinetics. Total membrane current was fitted to model-generated experimental data using a 'data-clamp' protocol. The experimental data consisted of a default action-potential waveform and an optional series of perturbed waveforms generated by current injections. Local parameter identifiability was ascertained from the reciprocal condition value (1/lambda) of the Hessian at the known solution. When fitting to a single action potential waveform, the model was found to be over-determined, having a 1/lambda value of approximately 3.6e-14. This value improved slightly to approximately 1.4e-10 when an additional 2 perturbed waveforms were included in the fitting process, suggesting that the additional data did not overly improve the identifiability problem. The additional data, however, did allow the accurate reconstruction of all ionic currents. This indicates that by appropriate experimental design, it may be possible to infer the properties of underlying membrane currents from observation of transmembrane potential waveforms perturbed by pseudo-random currents.

Action Potentials↗

PubMedDate not supplied

Contribution to the theory of prosthetic vision.

By way of extracellular, electrical stimulation of the visual pathway, the various approaches to vision prosthesis aim to provide crude, patterned vision to individuals with profound blindness. Common to all approaches is the implantable electrode array and the rendering of phosphenes-the actuated percepts occupying the visual field of the implantee. Thus prosthetic vision may be simulated, and underlying theories as to how to render it efficacious developed. We review the field of simulated prosthetic vision. Furthermore, with retinal prosthesis in mind, we suggest a revised approach-an approach with regard to sampling theory, the vertebrate central visual pathway, and eye movements. The parallel development of prosthetic vision theory, explored via simulation and bioengineering issues surrounding neurostimulator design and implantation has bearing on the success of clinical trials by numerous groups in coming years.

Biomedical Engineering↗