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N Goldman

Publications and source records attributed to N Goldman.

At least 55 records · Page 3Linked to original sources
PubMed1994

Variance to mean ratio, R(t), for poisson processes on phylogenetic trees.

The ratio of expected variance to mean, R(t), of numbers of DNA base substitutions for contemporary sequences related by a "star" phylogeny is widely seen as a measure of the adherence of the sequences' evolution to a Poisson process with a molecular clock, as predicted by the "neutral theory" of molecular evolution under certain conditions. A number of estimators of R(t) have been proposed, all predicted to have mean 1 and distributions based on the chi 2. Various genes have previously been analyzed and found to have values of R(t) far in excess of 1, calling into question important aspects of the neutral theory. In this paper, I use Monte Carlo simulation to show that the previously suggested means and distributions of estimators of R(t) are highly inaccurate. The analysis is applied to star phylogenies and to general phylogenetic trees, and well-known gene sequences are reanalyzed. For star phylogenies the results show that Kimura's estimators ("The Neutral Theory of Molecular Evolution," Cambridge Univ. Press, Cambridge, 1983) are unsatisfactory for statistical testing of R(t), but confirm the accuracy of Bulmer's correction factor (Genetics 123: 615-619, 1989). For all three nonstar phylogenies studied, attained values of all three estimators of R(t), although larger than 1, are within their true confidence limits under simple Poisson process models. This shows that lineage effects can be responsible for high estimates of R(t), restoring some limited confidence in the molecular clock and showing that the distinction between lineage and molecular clock effects is vital.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1994

Phylogenetic analysis of the rpoB gene from the plastid-like DNA of Plasmodium falciparum.

Malaria and other Apicomplexan parasites harbour two extrachromosomal DNAs. One is mitochondrial and the other is a 35-kb circle with some plastid-like features but whose provenance and function is unknown. In addition to genes for rRNAs, tRNAs and ribosomal proteins, the 35-kb circular DNA of Plasmodium falciparum carries an rpoBC operon which encodes subunits of a eubacteria-like RNA polymerase. The phylogenetic analysis of the complete rpoB sequence presented here supports our inference that the 35-kb circle is the remnant of a plastid genome.

Amino Acid Sequence↗
PubMed1994

Health cards, maternal reports and the measurement of immunization coverage: the example of Guatemala.

Immunization against major childhood diseases has been an essential component of health policies in developing countries. However, despite its importance and the efforts invested by many organizations in promoting immunization programs, consistent and accurate measurement of immunization coverage has not yet been achieved. In this paper, we explore the implications of alternative methods of measuring immunization coverage rates in Guatemala, using data from the 1987 Encuesta Nacional de Salud Materno Infantil, and we consider the dangers of making inferences about levels and trends in coverage from cross-sectional data. The results indicate that (1) service statistics may well lead to overestimates of coverage; (2) survey estimates derived from health cards can also produce severely biased estimates; and (3) in spite of problems associated with maternal recall, mothers' reports of their children's vaccination status probably result in substantially improved estimates of immunization coverage.

Bias↗
PubMed1994

Comparison of models for nucleotide substitution used in maximum-likelihood phylogenetic estimation.

Using real sequence data, we evaluate the adequacy of assumptions made in evolutionary models of nucleotide substitution and the effects that these assumptions have on estimation of evolutionary trees. Two aspects of the assumptions are evaluated. The first concerns the pattern of nucleotide substitution, including equilibrium base frequencies and the transition/transversion-rate ratio. The second concerns the variation of substitution rates over sites. The maximum-likelihood estimate of tree topology appears quite robust to both these aspects of the assumptions of the models, but evaluation of the reliability of the estimated tree by using simpler, less realistic models can be misleading. Branch lengths are underestimated when simpler models of substitution are used, but the underestimation caused by ignoring rate variation over nucleotide sites is much more serious. The goodness of fit of a model is reduced by ignoring spatial rate variation, but unrealistic assumptions about the pattern of nucleotide substitution can lead to an extraordinary reduction in the likelihood. It seems that evolutionary biologists can obtain accurate estimates of certain evolutionary parameters even with an incorrect phylogeny, while systematists cannot get the right tree with confidence even when a realistic, and more complex, model of evolution is assumed.

Computer Simulation↗
PubMed1994

A codon-based model of nucleotide substitution for protein-coding DNA sequences.

A codon-based model for the evolution of protein-coding DNA sequences is presented for use in phylogenetic estimation. A Markov process is used to describe substitutions between codons. Transition/transversion rate bias and codon usage bias are allowed in the model, and selective restraints at the protein level are accommodated using physicochemical distances between the amino acids coded for by the codons. Analyses of two data sets suggest that the new codon-based model can provide a better fit to data than can nucleotide-based models and can produce more reliable estimates of certain biologically important measures such as the transition/transversion rate ratio and the synonymous/nonsynonymous substitution rate ratio.

Animals↗
PubMed1994

Childhood immunization and pregnancy-related services in Guatemala.

In this paper we examine the experience of one poor country, Guatemala, that provided childhood immunization partly through a major national campaign, and provided pregnancy-related services through government health facilities, during the 1980s. Specifically, we compare the breadth of coverage of these two types of services using national sample survey data collected in 1987. We then draw upon results of previous qualitative studies to explore the social, cultural, and organizational factors that may account for differences between the use of immunization and the use of pregnancy-related health services.

Child↗
PubMed1994

[Evaluation and extension of Markov process models for the evolution of DNA].

Markov process models of nucleotide substitution are evaluated. A model proposed by Lanave et al (1984), alleged to need no priori assumption about the substitution pattern, is found to have the assumption of reversibility. Calculations based on the 2-p, 4-p, and 6-p substitution schemes show that site variation of substitution speed leads to serious under-estimation of sequence divergence by various methods. Spatial pattern variation also leads to under-estimation, but the discrepancy is slight. A nonhomogeneous Markov process model is used to study the temporal variations of rates and it is shown that the estimated number of substitutions reflects a rate averaged over time. The implications of those results to evolutionary phylogenetics are discussed.

Biological Evolution↗
PubMed1993

Nucleotide, dinucleotide and trinucleotide frequencies explain patterns observed in chaos game representations of DNA sequences.

The chaos game representation (CGR) is a scatter plot derived from a DNA sequence, with each point of the plot corresponding to one base of the sequence. If the DNA sequence were a random collection of bases, the CGR would be a uniformly filled square; conversely, any patterns visible in the CGR represent some pattern (information) in the DNA sequence. In this paper, patterns previously observed in a variety of DNA sequences are explained solely in terms of nucleotide, dinucleotide and trinucleotide frequencies.

Base Sequence↗
PubMed1993

Statistical tests of models of DNA substitution.

Penny et al. have written that "The most fundamental criterion for a scientific method is that the data must, in principle, be able to reject the model. Hardly any [phylogenetic] tree-reconstruction methods meet this simple requirement." The ability to reject models is of such great importance because the results of all phylogenetic analyses depend on their underlying models--to have confidence in the inferences, it is necessary to have confidence in the models. In this paper, a test statistic suggested by Cox is employed to test the adequacy of some statistical models of DNA sequence evolution used in the phylogenetic inference method introduced by Felsenstein. Monte Carlo simulations are used to assess significance levels. The resulting statistical tests provide an objective and very general assessment of all the components of a DNA substitution model; more specific versions of the test are devised to test individual components of a model. In all cases, the new analyses have the additional advantage that values of phylogenetic parameters do not have to be assumed in order to perform the tests.

Animals↗
PubMed1993

Simple diagnostic statistical tests of models for DNA substitution.

The accuracy of models for DNA substitution used in phylogenetic analyses is becoming more important with the increasing availability and analysis of molecular sequence data. It is natural to look for ways of improving these models, and to do this in a planned manner it is useful to be able to identify features of sequences that may not be described adequately. In this paper, I describe three statistics which may give useful diagnostic information on departures from models' predictions. The statistical distributions of these statistics are discussed and simple significance tests are derived. These tests are based on the (estimated) phylogeny of the sequences and so have the advantage of using the information contained in this tree. Examples are given of the application of the new tests to Markov chain models describing the evolution of primate pseudogene sequences and small-subunit RNA sequences.

Animals↗
PubMed1993

Excess mortality among the unmarried: a case study of Japan.

Recent research has demonstrated that mortality patterns by marital status in Japan are different from corresponding patterns in other industrialized countries. Most notably, the magnitude of the excess mortality experienced by single Japanese has been staggering. For example, estimates of life expectancy for the mid-1900s indicate that single Japanese men and women had life expectancies between 15 and 20 years lower than their married counterparts. In addition, gender differences among single Japanese have been smaller than elsewhere, while those among divorced persons have been unanticipatedly large; and, the excess mortality of the Japanese single population has been decreasing over the past few decades in contrast to generally increasing differentials elsewhere. In this paper, we use a variety of data sources to explore several explanations for these unique mortality patterns in Japan. Undeniably, the traditional Japanese system of arranged marriages makes the process of selecting a spouse a significant factor. Evidence from anthropological studies and attitudinal surveys indicates that marriage is likely to have been and probably continues to be more selective with regard to underlying health characteristics in Japan than in other industrialized countries. However, causal explanations related to the importance of marriage and the family in Japanese society may also be responsible for the relatively high mortality experienced by singles and by divorced men.

Cause of Death↗
PubMed1993

Marriage selection and age patterns of mortality: a mathematical investigation.

"In this paper, we use simulation models to demonstrate the complexity of the relationship between the marriage selection process and the resulting RMRs [relative mortality ratios]. In particular, we show that marriage selection alone can produce a relative mortality ratio which remains large and relatively constant at ages far beyond the marriage span....Our general objective...is to determine the range of age patterns of relative mortality which could, in theory, result from marriage selection on the basis of health characteristics. We also evaluate the effects of variations in the marriage selection mechanisms on the resulting mortality patterns.... We develop and apply several simple mathematical models of the marriage selection process. In order to distinguish the potential consequences of marriage selection from marriage protection, we consider hypothetical populations in which causal effects are absent.... We begin by considering an extremely simple marriage selection process and subsequently explore a more realistic selection model based on recent death and marriage rates for Japan."

Age Factors↗
PubMed1993

Pentostatin increases the acute toxicity of high dose cyclophosphamide.

One dose of pentostatin was added to a standard cyclophosphamide (CY) based transplant regimen in two patients in an attempt to decrease the rate of non-engraftment in haploidentical allogeneic BMT. Despite a normal cardiac history and evaluation prior to transplant, both patients suffered fatal cardiac toxicity within 48 h of receiving the chemotherapy. This phenomenon was further investigated in an animal model. Laboratory rats were treated with progressive doses of CY in a range that produces acute cardiac toxicity. Successive groups of rats were treated with either pentostatin or fludarabine and CY at 400 mg/kg. Neither pentostatin nor fludarabine alone produced early mortality. However, a marked increase in early mortality was noted in those animals treated with pentostatin and high-dose CY. The addition of fludarabine did not increase the early toxicity of CY. Autopsy revealed no gross or microscopic abnormalities in the animals. The implications of adding agents that interfere with adenosine metabolism to CY based transplant regimens is discussed.

Adult↗
PubMed1993

Marriage selection and mortality patterns: inferences and fallacies.

Researchers have long wondered whether marital-status differences in mortality arise largely from selection mechanisms or from causal processes typically known as marriage protection. Unfortunately, many investigators have relied on aggregate patterns of mortality differentials--such as age schedules of excess mortality in the single population or the relationship between the level of excess mortality and the relative size of the single population--to make inferences about the relative importance of selection and causal processes. In this paper, a simple mathematical simulation model is used to demonstrate that many inferences derived from observed patterns are simply not justified. This finding highlights the importance of prospective data for assessing the relative importance of selection and causal factors in accounting for the excess mortality of the unmarried.

Adult↗
PubMed1991

[Use of a monthly calendar for collecting retrospective data on contraception: an evaluation of the experimental field studies of the Demographic and Health Surveys (DHS)].

A methodological experiment was conducted as part of the Demographic and Health Surveys (DHS) project to determine whether different approaches to measuring the same variables would yield similar results. The experiment consisted of the use of a new questionnaire, incorporating variants of many of the traditional approaches to the collection of demographic and health data. The experimental questionnaire was applied in 2 countries, Peru and the Dominican Republic at the same time as the standard survey. The most salient feature of this new questionnaire pregnancies, contraceptive practice, and postpartum, marriage, employment, and migration information. In this paper, the authors evaluate whether the use of the calendar in the experimental questionnaire improved the quality of the resulting information on contraception in the DHS surveys from the abovementioned countries. Specifically, the author determine whether the monthly calendar led to better estimates of contraceptive prevalence, failure, and discontinuation, and discuss the advantages and drawbacks of the calendar over the more standard approach. Results from this evaluation suggest that the major advantages of the calendar over the more standard questionnaire are 3-fold: it allows for more complete reports of use for periods prior to the survey; it allows for a detailed study of contraceptive use patterns; and it obtains information which is more internally consistent with other types of information. On the bases of these findings, the DHS project will include a calendar in the new standard questionnaire to be used in the 2nd round of surveys (DHS II).

Americas↗