Biomedical subjects

S A Frank

Publications and source records attributed to S A Frank.

At least 37 records · Page 2Linked to original sources

PubMed1996

Models of parasite virulence.

Several evolutionary processes influence virulence, the amount of damage a parasite causes to its host. For example, parasites are favored to exploit their hosts prudently to prolong infection and avoid killing the host. Parasites also need to use some host resources to reproduce and transmit infections to new hosts. Thus parasites face a tradeoff between prudent exploitation and rapid reproduction-a life history tradeoff between longevity and fecundity. Other tradeoffs among components of parasite fitness also influence virulence. For example, competition among parasite genotypes favors rapid growth to achieve greater relative success within the host. Rapid growth may, however, lower the total productivity of the local group by overexploiting the host, which is a potentially renewable food supply. This is a problem of kin selection and group selection. I summarize models of parasite virulence with the theoretical tools of life history analysis, kin selection, and epidemiology. I then apply the theory to recent empirical studies and models of virulence. These applications, to nematodes, to the extreme virulence of hospital epidemics, and to bacterial meningitis, show the power of simple life history theory to highlight interesting questions and to provide a rich array of hypotheses. These examples also show the kinds of conceptual mistakes that commonly arise when only a few components of parasite fitness are analysed in isolation. The last part of the article connects standard models of parasite virulence to diverse topics, such as the virulence of bacterial plasmids, the evolution of genomes, and the processes that influenced conflict and cooperation among the earliest replicators near the origin of life.

Animals↗

PubMed1996

Extending the multimedia patient record across the wide area network.

The Dept. of Veterans Affairs is developing and testing a wide area medical network with multimedia capabilities for coordination and consolidation of medical services across locations. The system is composed of multimedia information systems at individual medical centers connected by a high speed wide area network. The DHCP Imaging System, which has been in clinical use for six years, provides storage management and workstation acquisition and display of the multimedia data. Teleconsulting capability using a variety of mechanisms' is being prototyped and tested to meet medical staffing and consultation needs.

Computer Communication Networks↗

PubMed1995

Mutual policing and repression of competition in the evolution of cooperative groups.

Evolutionary theory has not explained how competition among lower level units is suppressed in the formation of higher-level evolutionary units. For example, the key problem of early evolution is small, individual replicators formed cooperative groups of sufficient complexity to allow accurate copying of the genetic material. The puzzle is why parasites did not subvert the formation of cells by obtaining benefits from the group without contributing to shared traits that enhance reproduction. These parasites would outcompete other replicators within the cell, disrupting reproductive fairness among subunits and destroying the functional coherence of the group. A similar problem arose at a later evolutionary stage with the orderly mendelian segregation of subunits (chromosomes) within cells, and reproductive fairness continued to be a problem in the evolution of insect and human societies. Here I present a simple model to show how reproductive fairness evolves among subunits to create functional coherence and higher-level units. Self-restraint, which evolves according to the kin-selection coefficient of relatedness, is not sufficient: mutual policing and enforcement of reproductive fairness are also required for the evolution of increasing social complexity.

Biological Evolution↗

PubMed1995

The origin of synergistic symbiosis.

A dominant theme in the history of life has been the evolutionary innovations of cooperative symbioses: the first genomes near the origin of life, integrated prokaryotic cells, the complex symbiotic communities that evolved into modern eukaryotic cells, lichens, mycorrhizae, and so on. In this paper, a model of cooperative symbiosis that shows a threshold condition for the evolution of cooperation is analyzed. The threshold is not easily passed, but cooperative evolution proceeds rapidly once a symbiosis overcomes the threshold. In the model presented here, each species has genetic variability for a symbiotic trait. The trait imposes a reproductive cost on its bearer but enhances the reproduction of its partner species. For example, in the origin of genetic systems, the trait may cause biochemical synergism for the rate of replication of primitive RNA strands as in Eigen and Schuster's hypercycle model. Models of growth are contrasted with synergism, which are most appropriate for the evolution of genetic systems and for mutualisms such as lichens, with the strategic and psychological applications of the Prisoner's Dilemma model.

Biological Evolution↗

PubMed1995

George Price's contributions to evolutionary genetics.

George Price studied evolutionary genetics for approximately seven years between 1967 and 1974. During that brief period Price made three lasting contributions to evolutionary theory; these were: (i) the Price Equation, a profound insight into the nature of selection and the basis for the modern theories of kin and group selection; (ii) the theory of games and animal behavior, based on the concept of the evolutionarily stable strategy; and (iii) the modern interpretation of Fisher's fundamental theorem of natural selection, Fisher's theorem being perhaps the most cited and least understood idea in the history of evolutionary genetics. This paper summarizes Price's contributions and briefly outlines why, toward the end of his painful intellectual journey, he chose to focus his deep humanistic feelings and sharp, analytical mind on abstract problems in evolutionary theory.

Animals↗

PubMed1995

Effects of aging on glucose regulation during wakefulness and sleep.

Glucose intolerance, reduced sleep efficiency, and disturbed circadian rhythmicity occur in aging. In normal young subjects, glucose regulation is modulated by sleep and circadian rhythmicity. To examine age-related alterations in the temporal pattern of glucose tolerance and insulin secretion, eight modestly overweight healthy older men, eight weight-matched young men, and six young lean men were studied during constant glucose infusion for 53 h. Levels of glucose, insulin, C-peptide, and growth hormone (GH) were measured every 20 min. Rates of insulin and GH secretion were calculated by deconvolution. In older volunteers, sleep ws shallow and more fragmented than in young subjects but was nevertheless associated with robust glucose elevations. However, postsleep increases of insulin secretion were markedly dampened. During wakefulness, the normal morning-to-evening increase in glucose was preserved in the elderly, but insulin secretion failed to increase proportionately. Thus decreased glucose tolerance in aging is associated with insulin resistance and also with a relative insensitivity of the beta-cell to the modulation of glucose regulation by sleep and circadian rhythmicity.

Adult↗

PubMed1995

An analysis of the appropriate use of the Caledon ambulance service in the Overberg. A short report.

The objective of this study was to determine the possible extent of the inappropriate use of the ambulances of the Caledon station of the Overberg Regional Services Council. The trip sheets of the ambulances for the period 1987-1990 were retrospectively analysed, and the appropriateness of calls prospectively determined over a 7-month period. The results showed that the vast majority of calls (68%) were of a non-emergency nature, and that only 34% of the trips warranted the use of a fully equipped emergency vehicle. Various cost-containment measures are suggested.

Ambulances↗

PubMed1994

Recognition and polymorphism in host-parasite genetics.

Genetic specificity occurs in many host-parasite systems. Each host can recognize and resist only a subset of parasites; each parasite can grow only on particular hosts. Biochemical recognition systems determine which matching host and parasite genotypes result in resistance or disease. Recognition systems are often associated with widespread genetic polymorphism in the host and parasite populations. I describe four systems with matching host-parasite polymorphisms: plant-pathogen interactions, nuclear-cytoplasmic conflict in plants, restriction enzymes in bacterial defence against viruses, and bacterial plasmids that compete by toxin production and toxin immunity. These systems highlight several inductive problems. For example, the observed patterns of resistance and susceptibility between samples of hosts and parasites are often used to study polymorphism. The detectable polymorphism by this method may be a poor guide to the actual polymorphism and to the underlying biochemistry of host-parasite recognition. The problem of using detectable polymorphism to infer the true nature of recognition and polymorphism is exacerbated by non-equilibrium fluctuations in allele frequencies that commonly occur in host-parasite systems. Another problem is that different matching systems may lead either to low frequencies of host resistance and common parasites, or to common resistance and rare parasites. Thus low levels of host resistance or rare parasites do not imply that parasitism is an unimportant evolutionary force on host diversity. Knowledge of biochemical recognition systems and dynamical analysis of models provide a framework for analysing the widespread polymorphisms in host-parasite genetics.

Animals↗

PubMed1994

Kin selection and virulence in the evolution of protocells and parasites.

The evolution of parasite virulence and the origin of cooperative genomes in primitive cells are both problems that balance cooperative and competitive interactions among symbionts. I analyse the trade-off among three correlated traits: competitiveness against other genotypes for resources within hosts (protocells), damage to the host (virulence), and rate of horizontal transmission from one host to another. All three life-history components are strongly influenced by kin selection. For example, when genetic relatedness within hosts is high, each genotype is competing for resources with closely related genotypes. This competition among relatives favours increased horizontal transmission to colonize new hosts and compete against non-relatives. My analysis shows that many aspects of parasite and protocell evolution must be studied with the theoretical tools of social evolution. I discuss extensions that are required for a general theory of symbiosis.

Animals↗

PubMed1994

Genetics of mutualism: the evolution of altruism between species.

Conditions are analyzed under which natural selection favors an individual to help another species at a cost to its own reproduction. Traditional models for the evolution of altruism between species focus on the genetic relatedness between the original donor and the recipients of return benefits from the mutualistic partner species. A more general model is analyzed here that focuses on the synergistic effects between partner species caused by genetic variability. The model shows that the spread of altruism is enhanced by spatial correlations between species in the genetic tendency to give aid to partners. These spatial correlations between species are similar to the kin selection coefficients of relatedness that determine the course of social evolution within species. The model also shows that natural selection and ecological dynamics can create genetic correlations between neighbors of different species, even when the initial spatial distributions of the species are uncorrelated. Genetic correlations between species may play an important role in the origin and maintenance of altruism between species.

Altruism↗

PubMed1993

Specificity versus detectable polymorphism in host-parasite genetics.

Detectable polymorphism of host resistance and parasite host range is a poor guide to the specificity of a host-parasite interaction. I analyse a simple haploid model to support this claim. The model assumes that the true specificity is 'matching-allele', in which each of n host alleles causes resistance to only one of n different parasite alleles. The detectable polymorphism in samples from a matching-allele system would lead one to infer the gene-for-gene specificity commonly observed in plant-pathogen interactions. Gene-for-gene and matching-allele specificity require very different fitness assumptions to explain observed patterns of polymorphism. Yet models for each type of specificity can easily be constructed that fit the available data. In addition, the currently favoured 'elicitor-receptor' model for the biochemistry of plant-pathogen recognition agrees equally well with gene-for-gene or matching-allele specificity. I do not claim that the simple matching-allele specificity is the correct model for plant-pathogen genetics. My point is that one cannot reconstruct both specificity and population history from patterns of resistance among host-parasite pairs in a sample. I draw two conclusions: first, inferred specificity and polymorphism are only useful when compared with a family of theoretical models; and secondly, biochemical models of specificity must be tested by their population genetic consequences.

Alleles↗

PubMed1993

The spatial location of EEG electrodes: locating the best-fitting sphere relative to cortical anatomy.

The location of the international 10-20 system electrode positions and 14 fiducial landmarks are described in cartesian coordinates (+/- 1.4 mm average accuracy). Six replications were obtained on 3 separate days from 4 normal subjects, who were compared to each other with a best-fit sphere algorithm. Test-retest reliability depended on the electrode position: the parasagittal electrodes were associated with greater measurement errors (maximum 7 mm) than midline locations. Location variability due to head shape was greatest in the temporal region, averaging 5 mm from the mean. For each subject's electrode locations a best-fitting sphere was determined (79-87 mm radius, 6% average error). A surface-fitting algorithm was used to transfer the electrode locations and best-fitting sphere to MR images of the brain and scalp. The center of the best-fitting sphere coincided with the floor of the third ventricle 5 mm anterior to the posterior commissure. The melding of EEG electrode location information with brain anatomy provides an empirical basis for associating hypothetical equivalent dipole locations with their anatomical substrates.

Adult↗

PubMed1992

A kin selection model for the evolution of virulence.

The costs and benefits of parasite virulence are analysed in an evolutionarily stable strategy (ESS) model. Increased host mortality caused by disease (virulence) reduces a parasite's fitness by damaging its food supply. The fitness costs of high virulence may be offset by the benefits of increased transmission or ability to withstand the host's defences. It has been suggested that multiple infections lead to higher virulence because of competition among parasite strains within a host. A quantitative prediction is given for the ESS virulence rate as a function of the coefficient of relatedness among co-infecting strains. The prediction depends on the quantitative relation between the costs of virulence and the benefits of transmission or avoidance of host defences. The particular mechanisms by which parasites can increase their transmission or avoid host defences also have a key role in the evolution of virulence when there are multiple infections.

Animals↗

PubMed1992

Models of plant-pathogen coevolution.

Plant populations are often genetically polymorphic for resistance to pathogens. The effectiveness of this resistance is limited because the pathogens are, in turn, polymorphic for virulence genes that can evade plant resistance. Theoretical models and intriguing preliminary data suggest that these plant-pathogen polymorphisms are maintained by continual cycles of coevolution within populations, combined with occasional immigration of new virulence and resistance genes from distant populations.

Biological Evolution↗

PubMed1991

Ecological and genetic models of host-pathogen coevolution.

A model is presented to analyse the forces that maintain genetic polymorphism in interactions between host plants and their pathogens. Genetic variability in hosts occurs for specific resistance to different pathogen races and variability in pathogens occurs for specific virulence to different host races. The model tracks both fluctuating population sizes and changing gene frequencies. Analyses over a range of parameters show that ecological and demographic factors, such as birth and death rates, often have a more profound effect on the amount of polymorphism than genetic parameters, such as the pleiotropic costs of resistance and virulence associated with different alleles. A series of simple measures are proposed to predict the amount of genetic polymorphism expected in particular host-pathogen interactions. These measures can be used to develop and test a comparative theory of genetic polymorphism in host-pathogen coevolution.

Biological Evolution↗

PubMed1990

When to copy or avoid an opponent's strategy.

Models of two-player games are analyzed in which contestants strive to maximize relative success (market share). Each contestant divides its resources among a set of investment strategies. For a particular investment strategy the contestants may receive different expected rates of return. Each strategy also returns to both contestants an additional payoff that is unpredictable. Depending on particular assumptions, a contestant may maximize relative success by copying or avoiding its opponent's allocation pattern. In other cases a contestant may be favored to diversify its investments equally among strategies and minimize its total variance in returns, or to invest only in one strategy and maximize its total variance in returns.

Animals↗

PubMed1990

The distribution of allelic effects under mutation and selection.

The Price (1970, 1972) equation is applied to the problem of describing the changes in the moments of allelic effects caused by selection, mutation and recombination at loci governing a quantitative genetic character. For comparable assumptions the resulting equations are the same as those obtained by different means by Barton & Turelli (1987; Turelli & Barton, 1989). The Price equation provides a natural framework within which to examine certain kinds of non-additive allelic effects, recombination and assortative mating. The use of the Price equation is illustrated by finding the equilibrium genetic variance under multiplicative dominance and epistasis and under assortative mating at an additive locus. The limitations of the use of recursion equations for the moments of allelic effects are also discussed.

Alleles↗

PubMed1990

The quantitative genetic consequences of pleiotropy under stabilizing and directional selection.

The independence of two phenotypic characters affected by both pleiotropic and nonpleiotropic mutations is investigated using a generalization of M. Slatkin's stepwise mutation model of 1987. The model is used to determine whether predictions of either the multivariate normal model introduced in 1980 by R. Lande or the house-of-cards model introduced in 1985 by M. Turelli can be regarded as typical of models that are intermediate between them. We found that, under stabilizing selection, the variance of one character at equilibrium may depend on the strength of stabilizing selection on the other character (as in the house-of-cards model) or not (as in the multivariate normal model) depending on the types of mutations that can occur. Similarly, under directional selection, the genetic covariance between two characters may increase substantially (as in the house-of-cards model) or not (as in the multivariate normal model) depending on the kinds of mutations that are assumed to occur. Hence, even for the simple model we consider, neither the house-of-cards nor the multivariate normal model can be used to make predictions, making it unlikely that either could be used to draw general conclusions about more complex and realistic models.

Genes↗