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Biomedical subjects

N D Evans

Publications and source records attributed to N D Evans.

10 recordsLinked to original sources

Glucose-dependent changes in NAD(P)H-related fluorescence lifetime of adipocytes and fibroblasts in vitro: potential for non-invasive glucose sensing in diabetes mellitus.

The aim of this study was to test the hypothesis that glucose can be monitored non-invasively by measuring NAD(P)H-related fluorescence lifetime of cells in an in vitro cell culture model. Autofluorescence decay functions were measured in 3T3-L1 adipocytes by time-correlated single-photon counting (excitation 370nm, emission 420-480nm). Free NADH had a two-exponential decay but cell autofluorescence fitted best to a three-exponential decay. Addition of 30mM glucose caused a 29% increase in autofluorescence intensity, a significantly shortened mean lifetime (from 7.23 to 6.73ns), and an increase in the relative amplitude and fractional intensity of the short-lifetime component at the expense of the two longer-lifetime components. Similar effects were seen with rotenone, an agent that maximizes mitochondrial NADH. 3T3-L1 fibroblasts stained with the fluorescent mitochondrial marker, rhodamine 123 showed a 16% quenching of fluorescence intensity when exposed to 30mM glucose, and an increase in the relative amplitude and fractional intensity of the short lifetime at the expense of the longer lifetime component. We conclude that, though the effect size is relatively small, glucose can be measured non-invasively in cells by monitoring changes in the lifetimes of cell autofluorescence or of a dye marker of mitochondrial metabolism. Further investigation and development of fluorescence intensity and lifetime sensing is therefore indicated for possible non-invasive metabolic monitoring in human diabetes.

3T3-L1 Cells↗

The structural identifiability and parameter estimation of a multispecies model for the transmission of mastitis in dairy cows.

A structural identifiability analysis is performed on a mathematical model for the coupled transmission of two classes of pathogen. The pathogens, classified as major and minor, are aetiological agents of mastitis in dairy cows that interact directly and via the immunological reaction in their hosts. Parameter estimates are available from experimental data for all but four of the parameters in the model. Data from a longitudinal study of infection are used to estimate these unknown parameters. A novel approach and application of structural identifiability analysis is combined in this paper with the estimation of cross-protection parameters using epidemiological data.

Animals↗

Fabrication of specimens of metamorphic magnetite crystals for field ion microscopy and atom probe microanalysis.

Field ion specimens have been successfully fabricated from samples of metamorphic magnetite crystals (Fe3O4) extracted from a polymetamorphosed, granulite-facies marble with the use of a focused ion beam. These magnetite crystals contain nanometer-scale, disk-shaped inclusions making this magnetite particularly attractive for investigating the capabilities of atom probe field ion microscopy (APFIM) for geological materials. Field ion microscope images of these magnetite crystals were obtained in which the observed size and morphology of the precipitates agree with previous results. Samples were analyzed in the energy compensated optical position-sensitive atom probe. Mass spectra were obtained in which peaks for singly ionized 16O, 56Fe and 56FeO and doubly ionized 54Fe, 56Fe and 57Fe peaks were fully resolved. Manganese and aluminum were observed in a limited analysis of a precipitate in an energy compensated position sensitive atom probe.

Journal Article↗

An identifiability analysis of a parent-metabolite pharmacokinetic model for ivabradine.

The paper considers the structural identifiability of a parent-metabolite pharmacokinetic model for ivabradine and one of its metabolites. The model, which is linear, is considered initially for intravenous administration of ivabradine, and then for a combined intravenous and oral administration. In both cases, the model is shown to be unidentifiable. Simplification of the model (for both forms of administration) to that proposed by Duffull et al. (1) results in a globally structurally identifiable model. The analysis could be applied to the modeling of any drug undergoing first-pass metabolism, with plasma concentrations available from drug and metabolite.

Administration, Oral↗

A control theoretic approach to containing the spread of rabies.

Many problems in medicine and biology involve some kind of spatial spread, and quite often the need to control it. A large proportion of medical and biological systems distinguish themselves from those found in engineering by the way the control acts. We illustrate this by considering the specific example of the spread of rabies among foxes. We first give a brief description of a model proposed by Murray et al. (Murray, J. D., Stanley, E. A. & Brown, D. L., Proc. R. Soc. Lond., B 229, 111-150 (1986)), which we extend to include the control mechanism. The problem is to prevent the spread of rabies by vaccinating foxes via the distribution of bait in a region around an observed outbreak. The extended model can be formulated as a nonlinear time-varying control system described by partial differential equations. In contrast to most engineering type control problems, the control does not continuously affect the system but only acts through the initial distributions. We briefly outline a general theory developed for dealing with such nonlinear systems by the use of a fixed point theorem. The problem and the theory are illustrated by some numerical simulations.

Animals↗

Extensions to a procedure for generating locally identifiable reparameterisations of unidentifiable systems.

In this paper extensions to an existing procedure for generating locally identifiable reparameterisations of unidentifiable systems are presented. These extensions further formalise the constructive nature of the methodology and lend themselves to application within symbolic manipulation packages. The extended reparameterisation procedure is described in detail and is illustrated with application to two known non-trivial examples of unidentifiable systems of practical relevance.

Bioreactors↗

Mechanical and morphological variation of the human lumbar vertebral cortical and trabecular bone.

The nanoindentation technique was used to characterize the variation in the elastic modulus and hardness of human lumbar vertebral cortical and trabecular bone. The elastic modulus (and in most cases, the hardness as well) of axially aligned trabeculae cut in the transverse direction was significantly greater than in other orientations of vertebral cortical and trabecular bone. In all cases, the elastic modulus and hardness of bone in the load-bearing direction was greater than in corresponding bone types cut in the other directions. Scanning electron micrographs of cortical shell revealed the Haversian-like canal systems expected in secondary cortical bone, but it was difficult to differentiate by morphology cortical from trabecular bone in the human lumbar vertebrae.

Aged↗

Mandibular reconstruction using vascularised fibula.

The osteocutaneous fibula flap has been used to reconstruct large segments of mandible in cases following ablation for cancer or radionecrosis. The bone can be cut to the appropriate shape and the fasciocutaneous flap may be used simultaneously to provide oral cavity lining or skin cover. The technique is described and its successful use in seven patients is reported with details of the complications encountered.

Adult↗

Neonatal cortisol response to circumcision with anesthesia.

Eleven male newborns were circumcised with a local dorsal penile nerve block, and 13 controls were circumcised without anesthetic. Matched pairs of pre- and postcircumcision cortisol levels in the two groups were compared. The adrenal cortisol response to surgery was not significantly reduced by the administration of lidocaine. Blood sampling and anesthetic injection of venipuncture alone did not evoke the adrenal response in uncircumcised control infants. Cortical input or secondary epinephrine elevation may be producing the cortisol elevation in infants despite regional blockage of the afferent nerve pathways.

Adrenal Glands↗

The structural identifiability and parameter estimation of a multispecies model for the transmission of mastitis in dairy cows with postmilking teat disinfection.

A mathematical model for the transmission of two interacting classes of mastitis causing bacterial pathogens in a herd of dairy cows is presented and applied to a specific data set. The data were derived from a field trial of a specific measure used in the control of these pathogens, where half the individuals were subjected to the control and in the others the treatment was discontinued. The resultant mathematical model (eight non-linear simultaneous ordinary differential equations) therefore incorporates heterogeneity in the host as well as the infectious agent and consequently the effects of control are intrinsic in the model structure. A structural identifiability analysis of the model is presented demonstrating that the scope of the novel method used allows application to high order non-linear systems. The results of a simultaneous estimation of six unknown system parameters are presented. Previous work has only estimated a subset of these either simultaneously or individually. Therefore not only are new estimates provided for the parameters relating to the transmission and control of the classes of pathogens under study, but also information about the relationships between them. We exploit the close link between mathematical modelling, structural identifiability analysis, and parameter estimation to obtain biological insights into the system modelled.

Animals↗