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Biomedical subjects

A McCulloch

Publications and source records attributed to A McCulloch.

At least 19 recordsLinked to original sources

Most commercial insulin assays fail to detect recombinant insulin analogues.

Insulin assays are utilized in various clinical scenarios, including the assessment of insulin therapy compliance or of suspected insulin overdose. In an interpretative exercise carried out by UK National External Quality Assessment Service (NEQAS), serum sent to the participating laboratories was spiked with 30 pmol/L of the short-acting insulin analogue Human Actrapid. Only two out of 24 participant laboratories had sufficient assay cross-reactivity with Actrapid to interpret the results as suggestive of insulin administration. The development of specific insulin assays has led to deterioration in the ability to detect non-compliance or overdose with recombinant insulin treatment. Clinicians should be aware of this significant limitation, which could lead to misdiagnosis.

Adolescent↗

Chloroform in the environment: occurrence, sources, sinks and effects.

The chloroform flux through the environment is apparently constant at some 660+/-220 Ggyr(-1) (+/-1sigma) and about 90% of the emissions are natural in origin: the largest single source being in offshore sea water (contributing 360+/-90 Ggyr(-1)), with soil processes the next most important (220+/-100 Ggyr(-1)). Other natural sources, mainly volcanic and geological, account for less than 20 Ggyr(-1). The non-natural sources total 66+/-23 Ggyr(-1) and are much better characterised than the natural sources. They are predominantly the result of using strong oxidising agent on organic material in the presence of chloride ion, a direct parallel with the natural processes occurring in soils. Chloroform partitions preferentially into the atmosphere; the equilibrium distribution is greater than 99% and the average global atmospheric concentration has been calculated to be 18.5 pmolmol(-1). Atmospheric oxidation, the principal removal process, is approximately in balance with the identified source fluxes. Chloroform is widely dispersed in the aquatic environment (even naturally present in some mineral waters). Consequently, it is also widely dispersed in the tissue of living creatures and in foodstuffs but there is little evidence of bioaccumulation and the quantities in foodstuffs and drinking water are not problematical for human ingestion at the highest concentrations found. Definitive studies have shown that current environmental concentrations of chloroform do not present an ecotoxicological risk, even to fish at the embryonic and larval stages when they are most susceptible. By virtue of the very small amounts that actually become transported to the stratosphere, chloroform does not deplete ozone materially, nor is it a photochemically active volatile organic compound (VOC). It has a global warming potential that is less than that of the photochemically active VOCs and is not classed as a greenhouse gas.

Chloroform↗

Trichloroacetic acid in the environment.

Suppositions that the trichloroacetic acid (TCA, CCl3C(O)OH) found in nature was a consequence solely of the use of chlorinated hydrocarbon solvents prompted this critical review of the literature on its environmental fluxes and occurrences. TCA is widely distributed in forest soils (where it was rarely used as an herbicide) and measurements suggest a soil flux of 160 000 tonnes yr(-1) in European forests alone. TCA is also produced during oxidative water treatment and the global flux could amount to 55 000 tonnes yr(-1) (from pulp and paper manufacture, potable water and cooling water treatments). By contrast, the yields of TCA from chlorinated hydrocarbon solvents are small: from tetrachloroethene 13 600 tonnes yr(-1) and from 1,1,1-trichloroethane 4300 tonnes yr(-1) on a global basis, at the atmospheric burdens and removal rates typical of the late 1990s. TCA is ubiquitous in rainwater and snow. Its concentrations are highly variable and the variations cannot be connected with location or date. However, there is no significant difference between the concentrations found in Chile and in eastern Canada (by the same analysts), or between Malawi and western Canada, or between Antarctica and Switzerland, nor any significant difference globally between the concentrations in cloud, rain and snow (although local enhancement in fog water has been shown). TCA is present in old ice and firn. At the deepest levels, the firn was deposited early in the 19th century, well before the possibility of contamination by industrial production of reactive chlorine, implying a non-industrial background. This proposition is supported by plume measurements from pulp mills in Finland. TCA is ubiquitous in soils; concentrations are very variable but there are some indications that soils under coniferous trees contain higher amounts. The concentrations of TCA found in plant tissue are region-specific and may also be plant-specific, to the extent that conifers seem to contain more than other species. TCA is removed from the environment naturally. There is abundant evidence that soil microorganisms dehalogenate TCA and it is lost from within spruce needles with a half-life of 10 days. There is also recent evidence of an abiotic aqueous decarboxylation mechanism with a half-life of 22 days. The supposedly widespread effects of TCA in conifer needles are not shown in controlled experiments. At concentrations in the needles of Scots pine similar to those observed in needles in forest trees, changes consequent on TCA treatment of field laboratory specimens were almost all insignificant.

Caustics↗

Evidence for substantial variations of atmospheric hydroxyl radicals in the past two decades.

The hydroxyl radical (OH) is the dominant oxidizing chemical in the atmosphere. It destroys most air pollutants and many gases involved in ozone depletion and the greenhouse effect. Global measurements of 1,1,1-trichloroethane (CH3CCl3, methyl chloroform) provide an accurate method for determining the global and hemispheric behavior of OH. Measurements show that CH3CCl3 levels rose steadily from 1978 to reach a maximum in 1992 and then decreased rapidly to levels in 2000 that were lower than the levels when measurements began in 1978. Analysis of these observations shows that global OH levels were growing between 1978 and 1988, but the growth rate was decreasing at a rate of 0.23 +/- 0.18% year(-2), so that OH levels began declining after 1988. Overall, the global average OH trend between 1978 and 2000 was -0.64 +/- 0.60% year(-1). These variations imply important and unexpected gaps in current understanding of the capability of the atmosphere to cleanse itself.

Journal Article↗

Model study of ATP and ADP buffering, transport of Ca(2+) and Mg(2+), and regulation of ion pumps in ventricular myocyte.

We extended the model of the ventricular myocyte by Winslow et al. (Circ. Res 1999, 84:571-586) by incorporating equations for Ca(2+) and Mg(2+) buffering and transport by ATP and ADP and equations for MgATP regulation of ion transporters (Na(+)-K(+) pump, sarcolemmal and sarcoplasmic Ca(2+) pumps). The results indicate that, under normal conditions, Ca(2+) binding by low-affinity ATP and diffusion of CaATP may affect the amplitude and time course of intracellular Ca(2+) signals. The model also suggests that a fall in ATP/ADP ratio significantly reduces sarcoplasmic Ca(2+) content, increases diastolic Ca(2+), lowers systolic Ca(2+), increases Ca(2+) influx through L-type channels, and decreases the efficiency of the Na(+)/Ca(2+) exchanger in extruding Ca(2+) during periodic voltage-clamp stimulation. The analysis suggests that the most important reason for these changes during metabolic inhibition is the down-regulation of the sarcoplasmic Ca(2+)-ATPase pump by reduced diastolic MgATP levels. High Ca(2+) concentrations developed near the membrane might have a greater influence on Mg(2+), ATP, and ADP concentrations than that of the lower Ca(2+) concentrations in the bulk myoplasm. The model predictions are in general agreement with experimental observations measured under normal and pathological conditions.

Adenosine Diphosphate↗

Neighbourhood and family influences on the cognitive ability of children in the British National Child Development Study.

This paper investigates the association between family poverty, the level of deprivation in electoral wards and children's cognitive test scores using data from the second generation in the 1991 sweep of the British National Child Development Study (1958 birth cohort). Family poverty has a significant association with lower test scores in children of all ages (4-18 years). Neighbourhood poverty has a significant association with lower test scores in children aged 4-5 years which, though somewhat attenuated, is independent of other socioeconomic indicators. Among children aged between 6 and 9 years, the association with neighbourhood deprivation is statistically accounted for by individual characteristics. Among children aged between 10 and 18 years, levels of neighbourhood deprivation were for the most part statistically insignificant. The family poverty--test score association among children aged between 10 and 18 years was mediated by the home environment. Mediated effects were stronger for family poverty--test score associations than for neighbourhood poverty. The use of a neighbourhood-level exposure related to the social environment leads to an understanding of the social determinants of children's outcomes that is more than the sum of individual and family-level measures. However, the size of the estimated effects of neighbourhood conditions is much smaller than the estimated effects of family-level conditions. Thus, it appears that families still should be viewed as the key agents in promoting positive development in children.

Child↗

Teenage childbearing in Great Britain and the spatial concentration of poverty households.

STUDY OBJECTIVE: To investigate the association between the spatial concentration of deprived households and teenage non-marital childbearing. Associations with area deprivation are tested before and after allowing for levels of personal deprivation. DESIGN AND SETTING: The individual data are derived from the 2% sample of anonymised records (SAR) from the census of 1991 in Great Britain, and are combined with area data from the 278 districts of residence identifiable in the SAR. PARTICIPANTS: Sample is restricted to unmarried women living at home (with at least one parent) and aged 16 to 19. MAIN RESULTS: The results suggest generally higher risk of teenage childbearing for women who are economically inactive, women from households with no access to a car or households resident in local authority accommodation. Without adjusting for personal circumstances, the risk of teenage pregnancy shows a clear, significant and approximately linear association with social deprivation of area of residence in 1991. Residual analysis shows that many urban areas have much higher levels of teenage childbearing than expected. When adjustment is made for personal disadvantage the simple association with local area deprivation is attenuated. A higher risk of teenage childbearing is still seen in urban areas while the areas having the highest negative differentials are heterogeneous. CONCLUSIONS: Both individual and spatial characteristics are important in influencing levels of teenage childbearing. Teenage childbearing shows an association with residence in more deprived areas. The association seems to be largely because residence in more deprived areas is associated with personal disadvantage, which increases the risk of teenage childbearing. Area characteristics are of lesser significance in determining teenage non-marital childbearing than individual and household characteristics.

Adolescent↗

Flux-balance analysis of mitochondrial energy metabolism: consequences of systemic stoichiometric constraints.

Mitochondrial metabolism is a critical component in the functioning and maintenance of cellular organs. The stoichiometry of biochemical reaction networks imposes constraints on mitochondrial function. A modeling framework, flux-balance analysis (FBA), was used to characterize the optimal flux distributions for maximal ATP production in the mitochondrion. The model predicted the expected ATP yields for glucose, lactate, and palmitate. Genetic defects that affect mitochondrial functions have been implicated in several human diseases. FBA can characterize the metabolic behavior due to genetic deletions at the metabolic level, and the effect of mutations in the tricarboxylic acid (TCA) cycle on mitochondrial ATP production was simulated. The mitochondrial ATP production is severely affected by TCA-cycle mutations. In addition, the model predicts the secretion of TCA-cycle intermediates, which is observed in clinical studies of mitochondriopathies such as those associated with fumarase deficiency. The model provides a systemic perspective to characterize the effect of stoichiometric constraints and specific metabolic fluxes on mitochondrial function.

Adenosine Triphosphate↗

Integrated care. Primary dolours.

A primary care-led NHS has enjoyed gains, but at significant cost. The policy has failed to address public health issues, inequalities and problems in access to services. The policy has caused divisiveness and is seen as exacerbating deep-rooted competitiveness between GPs and consultants. A new concept is needed to unite the aspirations of the whole NHS.

Delivery of Health Care, Integrated↗

Fletcher Challenge-University of Auckland Heart & Health Study: design and baseline findings.

AIMS: The aims of this prospective observational study are to determine the relationship of sociodemographic factors, psychological factors and several factors measured in blood, with the risk of coronary heart disease (CHD) in a New Zealand population. METHODS: Participants were recruited from two sources: employees of the Fletcher Challenge Group and individuals listed on the general electoral roll for the Auckland region. Baseline and follow up risk factor data were obtained from a questionnaire, blood samples and a simple physical examination. Outcome data on deaths and hospitalisations due to coronary heart disease will be obtained primarily through linkage of participant identifiers to data collected nationally by the New Zealand Health Information Service. RESULTS: A total of 10,529 individuals agreed to participate (8011 from Fletcher Challenge and 2518 from the electoral roll), representing a response rate of 74%. Within the study population, there was a broad distribution of sociodemographic characteristics including ethnicity-10% of participants were Maori and 5% were of Pacific Islands origin. There was also wide heterogeneity of coronary heart disease risk as judged from the distributions of established risk factors at baseline-5% of participants had evidence of existing coronary heart disease, a quarter were current smokers, a sixth were nondrinkers, almost a half were overweight, a fifth had blood pressure > or = 150/95 mmHg or were receiving antihypertensive treatment and a sixth had cholesterol levels > or = 6.5 mmol/L. CONCLUSIONS: This is the first, large scale prospective observational study of the determinants of coronary heart disease in a New Zealand population. The study participants represent a broad cross section of society, with wide variation in sociodemographic characteristics and coronary heart disease risk. Initial results concerning the relationships of primary interest should be available within 5 years when sufficient coronary heart disease events have been documented to allow reliable analyses.

Adult↗

Large-scale finite element analysis of the beating heart.

The regional mechanics of the beating heart are directly related to factors such as ventricular pumping performance, coronary blood flow, myocardial energetics and oxygen consumption, vulnerability to ischemia and injury, hypertrophy and remodeling, and arrhythmogenesis. Important characteristics include: the complex three-dimensional geometry and fibrous architecture; the nonlinear, nonhomogeneous, anisotropic material properties of the myocardium; the hierarchical collagen connective tissue matrix; the time- and history-dependent active tension development of the cardiac muscle cells; and the three-dimensional anisotropic patterns of cardiac impulse propagation. To model these features realistically requires large-scale computational analysis with sophisticated numerical methods. As described in the chapter by Dr. Hunter and colleagues, an accurate three-dimensional finite element model has been developed to describe the geometry, fiber architecture, and extracellular matrix structure of the heart. The model is based on extensive anatomical measurements in the left and right ventricles (LV and RV) of the canine heart. In this chapter, we illustrate some new approaches to the special problems of large-scale finite element modeling in biomechanics using examples from the analysis of stress and electrical activation in the heart. Prospects for further progress--particularly in coupled problems such as cardiac electromechanics--are examined in light of new developments in high-performance computing.

Animals↗