Normative MEG data to flash and pattern reversal stimuli

We have attempted to establish normative values of components of the magnetic evoked field to flash and pattern reversal stimuli prior to clinical use of the MEG. Full visual field, binocular evoked magnetic fields were recorded from 100 subjects 16 to 86 years of age with a single channel dc Squid (BTI) second-order gradiometer at a point 5-6cm above the inion. The majority of subjects showed a large positive component (out going magnetic field) of mean latency 115 ms (SD range 2.5 -11.8 in different decades of life) to the pattern reversal stimulus. In many subjects, this P100M was preceeded and succeeded by negative deflections (in going field). About 6% of subjects showed an inverted response i.e. a PNP wave. Waveforms to flash were more variable in shape with several positive components; the most consistent having a mean latency of 110ms (SD range 6.4-23.2). Responses to both stimuli were consistent when measured on the same subject on six different occasions (SD range 4.8 to 7.3). The data suggest that norms can be established for evoked magnetic field components, in particular for the pattern reversal P100M, which could be used in the diagnosis of neuro-opthalmological disease.

The use of flash and pattern evoked fields in the diagnosis of Alzheimer's disease

Subjects with Alzheimer's disease (AD) exhibit normal visually evoked potentials (VEP) to pattern reversal stimuli but a delayed P2 flash response. The pattern response may originate in the primary visual cortex via the geniculo-calcarine pathway while the flash P2 may originate in the association areas via the cholinergic-tectal pathway. We now show: a) that the pathology of AD is more prominent in the visual association areas B18/19 than in B17 and b) that the magnetic signal to flash and pattern may originate from B18/19 and B17 respectively.

A study of cluster analysis techniques and their applications

This thesis seeks to describe the development of an inexpensive and efficient clustering technique for multivariate data analysis. The technique starts from a multivariate data matrix and ends with graphical representation of the data and pattern recognition discriminant function. The technique also results in distances frequency distribution that might be useful in detecting clustering in the data or for the estimation of parameters useful in the discrimination between the different populations in the data. The technique can also be used in feature selection. The technique is essentially for the discovery of data structure by revealing the component parts of the data. lhe thesis offers three distinct contributions for cluster analysis and pattern recognition techniques. The first contribution is the introduction of transformation function in the technique of nonlinear mapping. The second contribution is the us~ of distances frequency distribution instead of distances time-sequence in nonlinear mapping, The third contribution is the formulation of a new generalised and normalised error function together with its optimal step size formula for gradient method minimisation. The thesis consists of five chapters. The first chapter is the introduction. The second chapter describes multidimensional scaling as an origin of nonlinear mapping technique. The third chapter describes the first developing step in the technique of nonlinear mapping that is the introduction of "transformation function". The fourth chapter describes the second developing step of the nonlinear mapping technique. This is the use of distances frequency distribution instead of distances time-sequence. The chapter also includes the new generalised and normalised error function formulation. Finally, the fifth chapter, the conclusion, evaluates all developments and proposes a new program. for cluster analysis and pattern recognition by integrating all the new features.

The heteromeric 5-HT3A/B receptor:the effect of 5-HT3B subunits on receptor structure and ligand recognition

The 5-HT3 receptors are members of the cys-loop family of ligand-gated ion channels. Two functional subtypes are known, the homomeric 5HT3A and the heteromeric 5HT3A/B receptors, which exhibit distinct biophysical characteristics but are difficult to differentiate pharmacologically. Atomic force microscopy has been used to determine the stoichiometry and architecture of the heteromeric 5HT3A/B receptor. Each subunit was engineered to express a unique C-terminal epitope tag, together with six sequential histidine residues to facilitate nickel affinity purification. The 5-HT3 receptors, ectopically expressed in HEK293 cells, were solubilised, purified and decorated with antibodies to the subunit specific epitope tags. Imaging of individual receptors by atomic force microscopy revealed a pentameric arrangement of subunits in the order BBABA, reading anti-clockwise when viewed from the extracellular face. Homology models for the heteromeric receptor were then constructed using both the electron microscopic structure of the nicotinic acetylcholine receptor, from Torpedo marmorata, and the X-ray crystallographic structure of the soluble acetylcholine binding protein, from Lymnaea stagnalis, as templates. These homology models were used, together with equivalent models constructed for the homomeric receptor, to interpret mutagenesis experiments designed to explore the minimal recognition differences of both the natural agonist, 5-HT, and the competitive antagonist, granisetron, for the two human receptor subtypes. The results of this work revealed that the 5-HT3B subunit residues within the ligand binding site, for both the agonist and antagonist, are accommodating to conservative mutations. They are consistent with the view that the 5-HT3A subunit provides the principal and the 5-HT38 subunit the complementary recognition interactions at the binding interface.

Study of the cholinergic factors affecting the flash and pattern reversal visual evoked potentials

The effects of cholinergic agents undergoing clinical trials for the treatment of Alzheimer's disease and the anticholinergic agent scopolamine, were investigated on the components of the flash and pattern reversal visual evoked potentials (VEPs) in young healthy volunteers. The effect of recording the flash and pattern reversal VEPs for 13 hours in 5 healthy male volunteers, revealed no statistically significant change in the latency or amplitude measures. Administration of the muscarinic agonist SDZ 210-086 to 16 healthy male volunteers resulted in the reduction of the flash N2-P2 and pattern reversal N75-P100 peak-to-peak amplitudes. These effects on the flash VEP occurred at both doses (0.5 and 1.0 mg/day), but only at the higher dose on the pattern reversal VEP. Administration of the antimuscarinic agent scopolamine to 11 healthy young male volunteers, resulted in a delay of the flash P2 latency but no effect on the pattern reversal P100 latency. The pattern reversal N75-P100 peak-to-peak amplitude was also increased post dosing. The combination of scopolamine with the acetylcholinesterase inhibitor SDZ ENA 713 resulted in no significant effect on the flash and pattern reversal VEPs, suggesting that the effects of scopolamine may have been partially reversed. Topical application of scopolamine in 6 young healthy volunteers also resulted in no statistically significant effects on the flash and pattern reversal VEPs. The selective effect of scopolamine on the flash P2 latency but not on the pattern reversal P100 latency, provided a model whereby new cholinergic agents developed for the treatment of Alzheimer's disease can be investigated on a physiological basis. In addition, the results of this study led to the hypothesis that the selective flash P2 delay in Alzheimer's disease was probably due to a cholinergic deficit in both the tectal pathway from the retina to the visual cortex and the magnocellular path of the geniculostriate pathway, whereas the lack of an effect on the pattern reversal P100 component was probably due to a sparing of the parvocellular geniculostriate pathway.

Visual evoked magnetic responses (VEMR) to flash and pattern reversal stimulation

The problems of using a single channel magnetometer (BTi, Model 601) in an unshielded clinical environment to measure visual evoked magnetic responses (VEMR) were studied. VEMR to flash and pattern reversal stimuli were measured in 100 normal subjects. Two components, the P100M to pattern reversal and P2M to flash, were measured successfully in the majority of patients. The mean latencies of these components in different decades of life were more variable than the visual evoked potentials (VEP) that have been recorded to these stimuli. The latency of the P100M appeared to increase significantly after about 55 years of age whereas little change occurred for the flash P2M. The effects of blur, check size, stimulus size and luminance intensity on the latency and amplitude of the VEMR were studied. Blurring a small (32') check significantly increased latency whereas blurring a large (70') check had little effect on latency. Increasing check size significantly reduced latency of the P100M but had little effect on amplitude. Increasing the field size decreases the latency and increases the amplitude of the P100M. Within a normal subject, most of the temporal variability of the P100M appeared to be associated with run to run variation rather than between recording sessions on the same day or between days. Reproducibility of the P100M was improved to a degree by employing a magnetically shielded room. Increasing flash intensity decreases the latency and increases the amplitude of the P2M component. The magnitude of the effects of varying stimulus parameters on the VEMR were frequently greater than is normally seen in the VEP. The topography of the P100M and P2M varied over the scalp in normal subjects. Full field responses to a large check could be explained as approximately the sum of the half field responses and were consistent with the cruciform model of the visual cortex. Preliminary source localisation data suggested a shallower source in the visual cortex for the flash P2M compared with the P100M. The data suggest that suitable protocols could be devised to obtain normative data of sufficient quality to use the VEMR to flash and pattern clinically.

Human-computer interaction and innovation in handheld, mobile and wearable technologies

Handheld and mobile technologies have witnessed significant advances in functionality, leading to their widespread use as both business and social networking tools. Human-Computer Interaction and Innovation in Handheld, Mobile and Wearable Technologies reviews concepts relating to the design, development, evaluation, and application of mobile technologies. Studies on mobile user interfaces, mobile learning, and mobile commerce contribute to the growing body of knowledge on this expanding discipline.

Solid-supported boronic acid conjugates for sugar and glycopeptide recognition

The Fmoc synthetic strategy was employed to synthesise two identical combinatorial peptide libraries on a hydrophilic PEG-PS resin. One library was appended with boronic acid moieties at two positionally-fixed locations. Successful inclusion of the boronic acid units was confirmed using a novel UV fluorescent colorimetric assay employing carminic acid as the dye compound. A study of the effect had by the resin-bound peptides bearing boronic acid groups on the binding characteristics of vancomycin, a medically relevant antibiotic glycoprotein, was conducted. In all, 132 library compounds were tested for their binding affinity with vancomycin, via immobilisation of the glycopeptide onto the solid support through hydrogen bonding or complexation with the boronic acid moieties. Subsequent cleavage via acidolysis afforded vancomycin containing solutions which were quantified by growth inhibition of methicillin susceptible Staphylococcus aureus. Comparison of the diameters of the resultant zones of inhibition and those produced by vancomycin of known concentrations afforded a means of calculating the vancomycin concentration of the cleavage solutions, and thereby determining the binding affinity of vancomycin to each peptide sequence. Five peptide sequences and twenty one of the peptidyl-boronic acid sequences showed zones of inhibition, demonstrating their reversible affinity for vancomycin. Three peptide sequences showed zones of inhibition in both libraries. The presence of boronic acid was therefore shown to impart, enhance, detract and remove the affinity of vancomycin to a range of resin-bound peptide sequences.

A common rule for integration and suppression of luminance contrast across eyes, space, time, and pattern

Visual perception begins by dissecting the retinal image into millions of small patches for local analyses by local receptive fields. However, image structures extend well beyond these receptive fields and so further processes must be involved in sewing the image fragments back together to derive representations of higher order (more global) structures. To investigate the integration process, we also need to understand the opposite process of suppression. To investigate both processes together, we measured triplets of dipper functions for targets and pedestals involving interdigitated stimulus pairs (A, B). Previous work has shown that summation and suppression operate over the full contrast range for the domains of ocularity and space. Here, we extend that work to include orientation and time domains. Temporal stimuli were 15-Hz counter-phase sine-wave gratings, where A and B were the positive and negative phases of the oscillation, respectively. For orientation, we used orthogonally oriented contrast patches (A, B) whose sum was an isotropic difference of Gaussians. Results from all four domains could be understood within a common framework in which summation operates separately within the numerator and denominator of a contrast gain control equation. This simple arrangement of summation and counter-suppression achieves integration of various stimulus attributes without distorting the underlying contrast code.

Polymers in drug delivery and molecular recognition

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Psychological cue use and implications for a clinical decision support system

Effective clinical decision making depends upon identifying possible outcomes for a patient, selecting relevant cues, and processing the cues to arrive at accurate judgements of each outcome's probability of occurrence. These activities can be considered as classification tasks. This paper describes a new model of psychological classification that explains how people use cues to determine class or outcome likelihoods. It proposes that clinicians respond to conditional probabilities of outcomes given cues and that these probabilities compete with each other for influence on classification. The model explains why people appear to respond to base rates inappropriately, thereby overestimating the occurrence of rare categories, and a clinical example is provided for predicting suicide risk. The model makes an effective representation for expert clinical judgements and its psychological validity enables it to generate explanations in a form that is comprehensible to clinicians. It is a strong candidate for incorporation within a decision support system for mental-health risk assessment, where it can link with statistical and pattern recognition tools applied to a database of patients. The symbiotic combination of empirical evidence and clinical expertise can provide an important web-based resource for risk assessment, including multi-disciplinary education and training. © 2002 Informa UK Ltd All rights reserved.