The mass casualty situation affecting the USS Kitty Hawk.
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Color↗
Biomedical subjects
P A Carter
Publications and source records attributed to P A Carter.
The evolution of aging and age-related physical decline in mice selectively bred for high voluntary exercise.
We tested whether selective breeding for early-age high voluntary exercise behavior over 16 generations caused the evolution of lifelong exercise behavior, life expectancy, and age-specific mortality in house mice (Mus domesticus). Sixteenth-generation mice from four replicate selection lines and four replicate random-bred control lines were individually housed from weaning through death and divided between two activity treatments (either with or without running wheels). Thus, there were four treatment groups: selection versus control crossed with active versus sedentary. The effects of selective breeding on life expectancy and age-specific mortality differed between females and males. In females, sedentary selection mice had early and high initial adult mortality and thus the lowest increases in mortality with age. Active selection females had the lowest early adult mortality, had limited mortality during midlife, and exhibited rapid increases in mortality rates at the very end of life; thus, they had deferred senescence. Median life expectancy was greater for both groups of selection females than for the two complementary groups of control females. Like females, sedentary selection males had the highest early adult mortality, and slow but steadily increasing mortality over the entire lifetime. Unlike the active selection females, active control males had the lowest mortality across the lifespan (until the end of life). Interestingly, the males with the lowest median life expectancy were those in the active selection treatment group. In both sexes, running (km/week) decreased over the lifetime to very low and virtually equivalent levels at the end of life in control and selection mice. Overall, these results demonstrate an evolutionary cost of selective breeding for males, regardless of exercise level, but a benefit for females when they have an outlet for the up-selected behavior. We conclude that correlated evolution of senescence occurs in mice selectively bred for high voluntary wheel running; exercise per se is beneficial for control mice of both sexes, but the impact on the effect of selection depends on sex; and the behavioral effect of exercise selection at an early age declines throughout the life span, which demonstrates decreasing genetic correlations over age for the genes involved in increased exercise.
Aging↗
Molecular and quantitative genetic divergence among populations of house mice with known evolutionary histories.
Evolutionary biologists have long been interested in the processes influencing population differentiation, but separating the effects of neutral and adaptive evolution has been an obstacle for studies of population subdivision. A recently developed method allows tests of whether disruptive (ie, spatially variable) or stabilizing (ie, spatially uniform) selection is influencing phenotypic differentiation among subpopulations. This method, referred to as the F(ST) vs Q(ST) comparison, separates the total additive genetic variance into within- and among-population components and evaluates this level of differentiation against a neutral hypothesis. Thus, levels of neutral molecular (F(ST)) and quantitative genetic (Q(ST)) divergence are compared to evaluate the effects of selection and genetic drift on phenotypic differentiation. Although the utility of such comparisons appears great, its accuracy has not yet been evaluated in populations with known evolutionary histories. In this study, F(ST) vs Q(ST) comparisons were evaluated using laboratory populations of house mice with known evolutionary histories. In this model system, the F(ST) vs Q(ST) comparisons between the selection groups should reveal quantitative trait differentiation consistent with disruptive selection, while the F(ST) vs Q(ST) comparisons among lines within the selection groups should suggest quantitative trait differentiation in agreement with drift. We find that F(ST) vs Q(ST) comparisons generally produce the correct evolutionary inference at each level in the population hierarchy. Additionally, we demonstrate that when strong selection is applied between populations Q(ST) increases relative to Q(ST) among populations diverging by drift. Finally, we show that the statistical properties of Q(ST), a variance component ratio, need further investigation.
Animals↗
Genetic covariance structure of growth in the salamander Ambystoma macrodactylum.
The size of an organism at any point during ontogeny often has fitness consequences through either direct selection on size or through selection on size-related morphological, performance, or life history traits. However, the evolutionary response to selection on size across ontogeny (a growth trajectory) may be limited by genetic correlations across ages. Here we characterize the phenotypic and genetic covariance structure of length and mass growth trajectories in a natural population of larval Ambystoma macrodactylum using function-valued quantitative genetic analyses and principal component decomposition. Most of the phenotypic and genetic variation in both growth trajectories appears to be confined to a single principal component describing a pattern of positive covariation among sizes across all ages. Higher order principal components with no significant associated genetic variation were identified for both trajectories, suggesting that evolution towards certain patterns of negative covariation between sizes across ages is constrained. The well-characterized positive relationship between size at metamorphosis and fitness in pond-breeding amphibians predicts that the across-age covariance structure will strongly limit evolution only if there is negative selection on size prior to metamorphosis. The pattern of genetic covariation observed in this study is similar to that observed in other vertebrate taxa, indicating that size may often be highly genetically and phenotypically integrated across ontogeny. Additionally, we find that phenotypic and genetic analyses of growth trajectories can yield qualitatively similar patterns of covariance structure.
Animals↗
Lifelong voluntary exercise in the mouse prevents age-related alterations in gene expression in the heart.
We present the first quantitative gene expression analysis of cardiac aging under conditions of sedentary and active lifestyles using high-density oligonucleotide arrays representing 11,904 cDNAs and expressed sequence tags (ESTs). With these data, we test the hypothesis that exercise attenuates the gene expression changes that normally occur in the aging heart. Male mice (Mus domesticus) were sampled from the 16th generation of selective breeding for high voluntary exercise. For the selective breeding protocol, breeders were chosen based on the maximum number of wheel revolutions run on days 5 and 6 of a test at 8 wk of age. For the colony sampled herein, mice were housed individually over their entire lifetimes (from weaning) either with or without access to running wheels. The hearts of these two treatment groups (active and sedentary) were assayed at middle age (20 mo) and old age (33 mo). Genes significantly affected by age in the hearts of the sedentary population by at least a 50% expression change (n = 137) were distributed across several major categories, including inflammatory response, stress response, signal transduction, and energy metabolism. Genes significantly affected by age in the active population were fewer (n = 62). Of the 42 changes in gene expression that were common to both treatment groups, 32 (72%) displayed smaller fold changes as a result of exercise. Thus exercise offset many age-related gene expression changes observed in the hearts of the sedentary animals. These results suggest that adaptive physiological mechanisms that are induced by exercise can retard many effects of aging on heart muscle at the transcriptional level.
Age Factors↗
Dealing with the disturbed soldier in primary care.
Medical Officers are often called to review violent or disturbed soldiers in barracks or in their homes. Management of the acutely disturbed soldier differs from the acutely disturbed civilian in that, whilst drug therapy will be largely similar, application of the Mental Health Acts (1) varies depending on the soldier's situation and, in some cases, the Acts do not apply at all. In addition, the rules on the arrest and detention of soldiers have changed considerably since the introduction of Human Rights legislation (2).
Alcoholic Intoxication↗
The Diploma in Immediate Care of the Royal College of Surgeons of Edinburgh.
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Certification↗
Response of Sod-2 enzyme activity to selection for high voluntary wheel running.
The objective of this study was to examine the correlated response of anti-oxidant enzyme activity to selective breeding for increased voluntary wheel running in house mice. Activity of liver superoxide dismutase-2 (Sod-2), a free radical scavenger, was measured in four groups of mice. 'Active' individuals were housed in cages with attached wheels for 8 weeks beginning at weaning; 'sedentary' individuals were housed in cages with attached wheels that were prevented from rotating. Both of these treatments were applied to male and female mice from generation 14 of a replicated artificial selection experiment, which is composed of four lines selected for high wheel running and four randomly bred lines that serve as controls. In females, Sod-2 activity was significantly lower in selected vs control animals, regardless of presence/absence of a free-turning wheel. This difference suggests a trade-off between early-age voluntary wheel-running activity and Sod-2 activity. In males, Sod-2 activity was significantly affected by an interaction between selection group and activity group, with males from selected lines having lower Sod-2 activity relative to control males only in the sedentary treatment. These negative correlated responses of Sod-2 activity to selection on wheel running are discussed in the context of antagonistic pleiotropy models of aging and with respect to potential effects on lifespan.
Analysis of Variance↗
Receptor reserve of phosphoinositide-coupled muscarinic receptors in mouse hippocampus in vivo.
The ability of the partial muscarinic agonist pilocarpine to increase in vivo phosphoinositide (PI) hydrolysis in mouse brain was compared to two full agonists. Pilocarpine increased in vivo phosphoinositide (PI) hydrolysis in cortex, striatum, and to the greatest extent in the hippocampus. Pilocarpine injected either subcutaneously or intracerebroventricularly robustly increased in vivo PI hydrolysis in hippocampus up to 500% of control levels and the increases were blocked by the muscarinic antagonist scopolamine. The increases in vivo PI hydrolysis induced by pilocarpine were 60-75% of the magnitude of the full muscarinic agonists oxotremorine-M and cis-dioxolane. The muscarinic M(1) preferring antagonist pirenzepine potently blocked pilocarpine-induced increases in in vivo PI hydrolysis, consistent with the increase being mediated by M(1) receptors. Since pilocarpine is a relatively weak partial agonist, these data suggest a substantial level of receptor reserve for the PI response in mouse hippocampus.
Acetylcholine↗
Investigations into the physiological role of muscarinic M2 and M4 muscarinic and M4 receptor subtypes using receptor knockout mice.
Determination of muscarinic agonist-induced parasympathomimetic effects in wild type and M2 and M4 muscarinic receptor knockout mice revealed that M2 receptors mediated tremor and hypothermia, but not salivation. The M4 receptors seem to play a modest role in salivation, but did not alter hypothermia and tremor. In the M2 knockout mice, agonist-induced bradycardia in isolated spontaneously beating atria was completely absent compared to their wild type litter mates, whereas agonist-induced bradycardia was similar in the M4 knockout and wild type mice. The potency of carbachol to stimulate contraction of isolated stomach fundus, urinary bladder and trachea was reduced by a factor of about 2 in the M2 knockout mice, but was unaltered in the M4 knockout mice. The binding of the muscarinic agonist, [3H]-oxotremorine-M, was reduced in cortical tissue from the M2 knockout mice and to a lesser extent from the M4 knockout mice, and was reduced over 90% in the brain stem of M2 knockout mice. The data demonstrate the usefulness of knockout mice in determining the physiological function of peripheral and central muscarinic receptors.
Animals↗
Food consumption and body composition in mice selected for high wheel-running activity.
The effects of genetic selection for high wheel running (13th generation) and prolonged access (8 weeks) to running wheels on food consumption and body composition were studied in house mice (Mus domesticus). Mice from four replicate lines selected for high wheel-running activity ran over twice as many revolutions per day on activity wheels as did mice from four replicate control lines. At approximately 49 days of age, all mice were placed individually in cages with access to wheels and monitored for 6 days, after which wheels were prevented from rotating for the "sedentary" individuals. During the experiment, five feeding trials were conducted and body mass was measured weekly. After 8 weeks, body composition was measured by hydrogen isotope dilution. Across the five feeding trials, mice in the "active" group (wheels free to rotate) consumed 22.4% more food than mice in the "sedentary" group (wheels locked); mice from the selected lines consumed 8.4% more food than mice from the control lines (average of all trials; body mass-corrected values). In females, but not males, we found a significant interaction between selection and wheel access treatments: within the "active" group the difference in food consumption between selected and control animals was greater than in the "sedentary" group. At the end of the study, mice from the "active" and "sedentary" groups did not differ significantly in body mass; however, mice from the selected lines were approximately 6% smaller in body mass. Estimated lean body mass did not differ significantly either between selected and control lines or between wheel-access groups (P>0.3). Mice from selected lines had lower total body fat compared to mice from control lines (P=0.05; 24.5% reduction; LSMEANS) as did mice from the "active" compared to "sedentary" group (P= 0.03; 29.2% reduction; LSMEANS). Under these conditions, a sufficient explanation for the difference in body mass between the selected and control lines was the difference in fat content.
Animals↗
Open-field behavior of house mice selectively bred for high voluntary wheel-running.
Open-field behavioral assays are commonly used to test both locomotor activity and emotionality in rodents. We performed open-field tests on house mice (Mus domesticus) from four replicate lines genetically selected for high voluntary wheel-running for 22 generations and from four replicate random-bred control lines. Individual mice were recorded by video camera for 3 min in a 1-m2 open-field arena on 2 consecutive days. Mice from selected lines showed no statistical differences from control mice with respect to distance traveled, defecation, time spent in the interior, or average distance from the center of the arena during the trial. Thus, we found little evidence that open-field behavior, as traditionally defined, is genetically correlated with wheel-running behavior. This result is a useful converse test of classical studies that report no increased wheel-running in mice selected for increased open-field activity. However, mice from selected lines turned less in their travel paths than did control-line mice, and females from selected lines had slower travel times (longer latencies) to reach the wall. We discuss these results in the context of the historical open-field test and newly defined measures of open-field activity.
Animals↗
A not-so-silent cry for help. Older female cancer caregivers' need for information.
Cancer family caregivers face uncertainty every day. The holistic health care practitioner is in a unique position to alleviate some of this uncertainty by providing information. Although this may appear to be straightforward, unfortunately, more often than not, information is not provided or is provided in such a way that it is more harmful than helpful. This article presents findings from a qualitative study conducted with 21 older female caregivers of persons with advanced-stage cancer. Six areas of concern or need arose from the data and are presented with caregiver narrative examples. This article's purpose is not to be prescriptive (e.g., telling holistic health care practitioners what to say and how to say it). Instead, the purpose is to highlight the need for holistic health care practitioners to evaluate their caregivers' individual needs for information and to attempt to provide this information in a sensitive yet factually accurate manner.
Adaptation, Psychological↗
Maximum cold-induced food consumption in mice selected for high locomotor activity: implications for the evolution of endotherm energy budgets.
We studied house mice (Mus domesticus) that had been artificially selected for high activity to test the hypothesis that a high capacity for energy assimilation in cold-exposed endotherms could evolve as a correlated response to selection for increased locomotor activity. After 10 generations of selection for increased voluntary wheel-running, mice from four selected lines ran 75 % more wheel revolutions per day than did mice from four random-bred, control lines. The maximum cold-induced rates of food consumption (C(max); mean 10.6 g day(-1)) and energy assimilation (A(max); mean 141 kJ day(-1)) were not significantly higher in the selected than in the control mice. However, in cold-exposure trials, mice from the selected lines maintained body mass better than did mice from the control lines. C(max) and A(max) were positively correlated with the amount of wheel-running activity measured before cold-exposure and also with the rates of food consumption measured when the mice had access to running wheels. In females at least, the correlation was significant not only among individuals but also among adjusted means of the replicate lines, which suggests the presence of a positive genetic correlation between the traits. Thus, despite the lack of a significant difference between the selected and control lines in maximum rate of food consumption, the remaining results conform to the hypothesis that a selection for increased locomotor activity could be a factor behind the evolution of the ability to sustain activity and maintain energy balance during prolonged cold-exposure, as occurred during the evolution of mammalian and avian endothermy.
Animals↗
Predictors of social support and caregiver outcomes.
PURPOSE: This study identified predictors of caregiver's burden, satisfaction, depression, and social support. Little has been done to identify predictors of social support for caregivers at risk for negative outcomes. DESIGN: Correlational descriptive study. METHODS: A subset of interview data from a larger intervention study was utilized. Independent variables were caregiver/care-recipient characteristics and social support. Dependent variables included caregiver burden, satisfaction, depression, anxiety, and hostility. RESULTS: Eighty-one caregiver/care-recipient dyads from the community participated in this study. Caregivers were women with a mean age of 67.53 years (range 39-86). Difficulty arranging assistance from confidante or friends correlated significantly and positively with caregiver burden (r = .38; p <.001) and depression (r = .34; p = .002), and negatively with satisfaction (r = -.28; p = .013). FINDINGS/IMPLICATIONS: Arranging assistance is more important than frequency of social network contact with respect to burden and depression. The findings indicate a need for further investigation and the consideration of interventions for at risk caregivers.
Adult↗
Variation, selection and evolution of function-valued traits.
We describe an emerging framework for understanding variation, selection and evolution of phenotypic traits that are mathematical functions. We use one specific empirical example--thermal performance curves (TPCs) for growth rates of caterpillars - to demonstrate how models for function-valued traits are natural extensions of more familiar, multivariate models for correlated, quantitative traits. We emphasize three main points. First, because function-valued traits are continuous functions, there are important constraints on their patterns of variation that are not captured by multivariate models. Phenotypic and genetic variation in function-valued traits can be quantified in terms of variance-covariance functions and their associated eigenfunctions: we illustrate how these are estimated as well as their biological interpretations for TPCs. Second, selection on a function-valued trait is itself a function, defined in terms of selection gradient functions. For TPCs, the selection gradient describes how the relationship between an organism's performance and its fitness varies as a function of its temperature. We show how the form of the selection gradient function for TPCs relates to the frequency distribution of environmental states (caterpillar temperatures) during selection. Third, we can predict evolutionary responses of function-valued traits in terms of the genetic variance-covariance and the selection gradient functions. We illustrate how non-linear evolutionary responses of TPCs may occur even when the mean phenotype and the selection gradient are themselves linear functions of temperature. Finally, we discuss some of the methodological and empirical challenges for future studies of the evolution of function-valued traits.
Animals↗
Effect of contamination of pharmaceutical equipment on powder triboelectrification.
Triboelectrification of pharmaceutical powders may cause problems during processing and manufacture due to adhesion/cohesion effects. The aim of this work was to investigate the role of adhered particles and moisture as contact surface contaminants on the electrostatic charging of size fractionated lactose, following contact with a surface, i.e. stainless steel, typically used in pharmaceutical process and manufacturing operations. Replicated experimental runs without cleaning the contact surface showed a successive decrease in the net electronegative charge due to adhered lactose particles. Removal of these contaminating particles by different cleaning methods had a considerable effect on the charge after triboelectrification. The charge on the lactose samples was found to decrease when humidity in the cyclone apparatus was increased from 2 to 100% relative humidity. These results clearly demonstrate that moisture, particulate contamination and method of cleaning of processing equipment during pharmaceutical manufacturing operations may influence the electrostatic behaviour of powders.
Equipment Contamination↗
Evidence for a zinc/proton antiporter in rat brain.
The data presented in this paper are consistent with the existence of a plasma membrane zinc/proton antiport activity in rat brain. Experiments were performed using purified plasma membrane vesicles isolated from whole rat brain. Incubating vesicles in the presence of various concentrations of 65Zn2+ resulted in a rapid accumulation of 65Zn2+. Hill plot analysis demonstrated a lack of cooperativity in zinc activation of 65Zn2+ uptake. Zinc uptake was inhibited in the presence of 1 mM Ni2+, Cd2+, or CO2+. Calcium (1 mM) was less effective at inhibiting 65Zn2+ uptake and Mg2+ and Mn2+ had no effect. The initial rate of vesicular 65Zn2+ uptake was inhibited by increasing extravesicular H+ concentration. Vesicles preloaded with 65Zn2+ could be induced to release 65Zn2+ by increasing extravesicular H+ or addition of 1 mM nonradioactive Zn2+. Hill plot analysis showed a lack of cooperativity in H+ activation of 65Zn2+ release. Based on the Hill analyses, the stoichiometry of transport may include Zn2+/Zn2+ exchange and Zn2+/H+ antiport, the latter being potentially electrogenic. Zinc/proton antiport may be an important mode of zinc uptake into neurons and contribute to the reuptake of zinc to replenish presynaptic vesicle stores after stimulation.
Animals↗