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N Goldman

Publications and source records attributed to N Goldman.

At least 19 recordsLinked to original sources
PubMed2001

Molecular phylogenetics: state-of-the-art methods for looking into the past.

As the amount of molecular sequence data in the public domain grows, so does the range of biological topics that it influences through evolutionary considerations. In recent years, a number of developments have enabled molecular phylogenetic methodology to keep pace. Likelihood-based inferential techniques, although controversial in the past, lie at the heart of these new methods and are producing the promised advances in the understanding of sequence evolution. They allow both a wide variety of phylogenetic inferences from sequence data and robust statistical assessment of all results. It cannot remain acceptable to use outdated data analysis techniques when superior alternatives exist. Here, we discuss the most important and exciting methods currently available to the molecular phylogeneticist.

Animals↗
PubMed2001

Diffusion of ideas about personal hygiene and contamination in poor countries: evidence from Guatemala.

In this paper, we explore the diffusion of beliefs pertaining to the causes of childhood diarrhea in rural Guatemala. The analysis focuses on the importance of interpersonal and impersonal contacts as conduits for information and norms related to hygiene and contamination. Estimates from multivariate models reveal that there is evidence of a diffusion process through social contacts, primarily through interpersonal ones. The analysis also identifies striking differences between (1) the diffusion process related to hygiene (e.g. dirtiness) and that related to contamination (e.g. pathogens); and (2) beliefs about the causes of diarrheal illness among children in general and those among respondents' own children.

Adolescent↗
PubMed2001

Complete characterization of the (D2O)2 ground state: high Ka rotation-tunneling levels.

We report the observation of extensive a- and c-type rotation-tunneling (RT) spectra of (D2O)2 for Ka = 0-4. These data allow quantification of molecular constants and tunneling splittings for a number of previously unobserved RT states of (D2O)2. The vibrational ground state has thus been characterized to energies as high as those of some of the intermolecular vibrations, and we present the first test of the VRT(ASP-W) potential at these high Ka states.

Journal Article↗
PubMed2001

A general empirical model of protein evolution derived from multiple protein families using a maximum-likelihood approach.

Phylogenetic inference from amino acid sequence data uses mainly empirical models of amino acid replacement and is therefore dependent on those models. Two of the more widely used models, the Dayhoff and JTT models, are estimated using similar methods that can utilize large numbers of sequences from many unrelated protein families but are somewhat unsatisfactory because they rely on assumptions that may lead to systematic error and discard a large amount of the information within the sequences. The alternative method of maximum-likelihood estimation may utilize the information in the sequence data more efficiently and suffers from no systematic error, but it has previously been applicable to relatively few sequences related by a single phylogenetic tree. Here, we combine the best attributes of these two methods using an approximate maximum-likelihood method. We implemented this approach to estimate a new model of amino acid replacement from a database of globular protein sequences comprising 3,905 amino acid sequences split into 182 protein families. While the new model has an overall structure similar to those of other commonly used models, there are significant differences. The new model outperforms the Dayhoff and JTT models with respect to maximum-likelihood values for a large majority of the protein families in our database. This suggests that it provides a better overall fit to the evolutionary process in globular proteins and may lead to more accurate phylogenetic tree estimates. Potentially, this matrix, and the methods used to generate it, may also be useful in other areas of research, such as biological sequence database searching, sequence alignment, and protein structure prediction, for which an accurate description of amino acid replacement is required.

Algorithms↗
PubMed2001

Social inequalities in health disentangling the underlying mechanisms.

Differentials in health and longevity by socioeconomic status and by the nature of social relationships have been found in innumerable studies in the social and medical sciences. Three categories of explanations for the observed patterns have been proposed: causal mechanisms through which the social environment affects health status or the risk of dying; selection or reverse causal pathways whereby a person's health status affects their social position; and artifactual mechanisms, such as measurement error. The general consensus among researchers is that the observed disparities in health are driven largely by a complex set of causal processes rather than by selection or by artifactual mechanisms. This paper explores the set of arguments and strategies that researchers have used to arrive at this conclusion. As part of this undertaking, we assess whether inferences regarding the minor contribution of selection to the overall association between social factors and health are justifiable. In addition, we identify current avenues of research that are providing new insights into the causal pathways linking social factors and health.

Adult↗
PubMed2000

Do health interview surveys yield reliable data on chronic illness among older respondents?

Previous research evaluating quality of health interview survey data has generally relied upon comparisons of household interview data with medical records or other external sources of information. However, "gold standards" are not always satisfactory or available. This paper illustrates an alternative approach to the evaluation of data quality-examination of the reliability of reports of chronic conditions in longitudinal surveys. The data come from national samples of older Americans (First National Health and Nutrition Examination Survey Epidemiologic Followup Study, 1971-1975, 1982-1984, 1986) and older Taiwanese (Survey of Health and Living Status of the Elderly, 1989, 1993, 1996). The results show that, among respondents who reported a chronic condition at a given interview, the likelihood that the condition was acknowledged at the subsequent interview was higher for hypertension and diabetes than for arthritis and stroke. Low levels of consistency for stroke appear to result partly from the poor wording of questions. In Taiwan, younger, more educated persons and those experiencing severe conditions were somewhat more likely to acknowledge the condition at follow-up compared with their respective counterparts. Women and persons of high cognitive status in the United States and respondents in both countries who used a proxy to report the occurrence of a stroke were also more likely to acknowledge conditions at follow-up.

Adult↗
PubMed2000

A description of child illness and treatment behavior in Guatemala.

This paper uses a new calendar design implemented in the Guatemalan Survey of Family Health to analyze diarrheal and respiratory illness among children. The calendar provides a much richer description of child illness and treatment behavior than do conventional data typically collected in health interview surveys. The resulting estimates reveal that Guatemalan children experience high rates of diarrheal and respiratory illness and that these illnesses often involve multiple symptoms that only partially overlap one another. In addition, estimates from the calendar demonstrate that the measurement of illness frequency is fairly complex and that classification of illness into distinct categories may not always be feasible or meaningful. Results regarding treatment behavior indicate that the vast majority of illnesses are treated and that mothers almost always receive advice regarding their children's illnesses from relatives. On the other hand, health providers are sought for advice and treatment in only about one-third of illnesses. When families do seek providers, they are more likely to rely on biomedical ones - especially pharmacists, doctors and personnel at health posts and centers - than traditional practitioners. By far, the most common form of treatment - recommended by both relatives and providers - consists of readily available Western medicines. In contrast, the use of traditional remedies appears to be relatively low.

Attitude to Health↗
PubMed2000

The association between health-related behaviours and the risk of divorce in the USA.

This study investigates the link between health-related variables and risks of divorce. The findings indicate that physical characteristics associated with poor health--namely, obesity and short stature--are not significantly related to risks of marital dissolution for either men or women. On the other hand, risk-taking behaviours--such as smoking and drug use--are strongly related to higher risks of divorce for both sexes. Overall, the results emphasize the need to accommodate health-related variables in the dominant economic and social psychological theories of marital dissolution.

Adult↗
PubMed2000

Health-seeking behaviour for child illness in Guatemala.

Relying on data from the 1995 Guatemalan Survey of Family Health (EGSF), we analyse the relationship between child illness and health-seeking behaviour. Information on illness was collected for 3193 children. This analysis is based on 870 of these who became ill with diarrhoeal or respiratory disease during a 13-day period prior to interview. Estimates are derived from logistic models of the probability of seeing any or a specific type of health care provider as a function of characteristics of the illness on a given day and the child. The results indicate that modern medical care plays a major role in the treatment of infectious illness among children in rural Guatemala, with visits to pharmacists, doctors and the staff at government health facilities occurring much more frequently than visits to curers and other traditional practitioners. In general, families are much more likely to seek out a health care provider when a child experiences fever and gastrointestinal symptoms than when suffering from respiratory and other symptoms, and when a mother perceives the illness to be serious. The results also indicate that infants, low parity children, and children assessed as having generally been in good health are more likely to visit health care providers than other children. However, the particular associations often vary by type of health care provider.

Attitude to Health↗
PubMed2000

Likelihood-based tests of topologies in phylogenetics.

Likelihood-based statistical tests of competing evolutionary hypotheses (tree topologies) have been available for approximately a decade. By far the most commonly used is the Kishino-Hasegawa test. However, the assumptions that have to be made to ensure the validity of the Kishino-Hasegawa test place important restrictions on its applicability. In particular, it is only valid when the topologies being compared are specified a priori. Unfortunately, this means that the Kishino-Hasegawa test may be severely biased in many cases in which it is now commonly used: for example, in any case in which one of the competing topologies has been selected for testing because it is the maximum likelihood topology for the data set at hand. We review the theory of the Kishino-Hasegawa test and contend that for the majority of popular applications this test should not be used. Previously published results from invalid applications of the Kishino-Hasegawa test should be treated extremely cautiously, and future applications should use appropriate alternative tests instead. We review such alternative tests, both nonparametric and parametric, and give two examples which illustrate the importance of our contentions.

Classification↗
PubMed2000

Understanding ethnic variation in pregnancy-related care in rural Guatemala.

OBJECTIVES: This study examines the relatively low use of modern pregnancy-related care in Guatemala, especially among indigenous women, and explores the role of socioeconomic status, social and cultural variables, and access to biomedical health facilities in accounting for ethnic differences in care. METHODS: The data for the analysis come from the Guatemalan Survey of Family Health--a population-based survey of rural women that contains detailed data on care received during pregnancy and delivery along with extensive background information. Binomial and multinomial logit models are used to identify the variables that affect the likelihood of receiving different types of care during pregnancy and delivering in a medical facility and the extent to which sociocultural factors and measures of access account for the observed ethnic differences. RESULTS: The estimates not only confirm previous findings of a large ethnic difference in the use of modern pregnancy-related care, but also extend them by identifying a gradient within the indigenous population. The analysis demonstrates that, in general, sociocultural variables are more strongly associated with modern pregnancy-related care than are measures of access and that the former variables explain more of the ethnic variation in care than the latter. The results also demonstrate that pregnant women, especially indigenous women, are more likely to seek biomedical care in conjunction with traditional midwifery care rather than to rely solely on the former. CONCLUSION: The findings suggest that midwives are likely to continue to be key providers of pregnancy-related care in the future, even as access to modern health facilities improves. Current efforts directed toward the training and integration of midwives into the formal health system are likely to be much more effective at improving pregnancy-related care than the replacement of midwives with biomedical providers.

Adolescent↗
PubMed2000

EDIBLE: experimental design and information calculations in phylogenetics.

UNLABELLED: Although evolutionary inference from molecular sequences is a statistical problem, little attention has been paid to questions of experimental design. A computer program, EDIBLE, has been developed to perform likelihood calculations based on Markov process models of nucleotide substitution allied with phylogenetic trees, and from these to compute Fisher information measures under different experimental designs. These calculations can be used to answer questions of optimal experimental design in molecular phylogenetics. AVAILABILITY: Source code (ANSI C), executables and documentation for EDIBLE are available from http://ng-dec1.gen.cam. ac.uk/info/index.htmland 'downstream' Web pages. CONTACT: N.Goldman@gen.cam.ac.uk

Likelihood Functions↗
PubMed2000

Codon-substitution models for heterogeneous selection pressure at amino acid sites.

Comparison of relative fixation rates of synonymous (silent) and nonsynonymous (amino acid-altering) mutations provides a means for understanding the mechanisms of molecular sequence evolution. The nonsynonymous/synonymous rate ratio (omega = d(N)d(S)) is an important indicator of selective pressure at the protein level, with omega = 1 meaning neutral mutations, omega < 1 purifying selection, and omega > 1 diversifying positive selection. Amino acid sites in a protein are expected to be under different selective pressures and have different underlying omega ratios. We develop models that account for heterogeneous omega ratios among amino acid sites and apply them to phylogenetic analyses of protein-coding DNA sequences. These models are useful for testing for adaptive molecular evolution and identifying amino acid sites under diversifying selection. Ten data sets of genes from nuclear, mitochondrial, and viral genomes are analyzed to estimate the distributions of omega among sites. In all data sets analyzed, the selective pressure indicated by the omega ratio is found to be highly heterogeneous among sites. Previously unsuspected Darwinian selection is detected in several genes in which the average omega ratio across sites is <1, but in which some sites are clearly under diversifying selection with omega > 1. Genes undergoing positive selection include the beta-globin gene from vertebrates, mitochondrial protein-coding genes from hominoids, the hemagglutinin (HA) gene from human influenza virus A, and HIV-1 env, vif, and pol genes. Tests for the presence of positively selected sites and their subsequent identification appear quite robust to the specific distributional form assumed for omega and can be achieved using any of several models we implement. However, we encountered difficulties in estimating the precise distribution of omega among sites from real data sets.

Amino Acid Substitution↗
PubMed1999

Coevolving protein residues: maximum likelihood identification and relationship to structure.

The identification of protein sites undergoing correlated evolution (coevolution) is of great interest due to the possibility that these pairs will tend to be adjacent in the three-dimensional structure. Identification of such pairs should provide useful information for understanding the evolutionary process, predicting the effects of site-directed substitution, and potentially for predicting protein structure. Here, we develop and apply a maximum likelihood method with the aim of improving detection of coevolution. Unlike previous methods which have had limited success, this method allows for correlations induced by phylogenetic relationships and for variation in rate of evolution along branches, and does not rely on accurate reconstruction of ancestral nodes. In order to reduce the complexity of coevolutionary relationships and identify the primary component of pairwise coevolution between two sites, we reduce the data to a two-state system at each site, regardless of the actual number of residues observed at that site. Simulations show that this strategy is good at identifying simple correlations and at recognizing cases in which the data are insufficient to distinguish between coevolution and spurious correlations. The new method was tested by using size and charge characteristics to group the residues at each site, and then evaluating coevolution in myoglobin sequences. Grouping based on physicochemical characteristics allows categorization of coevolving sites into positive and negative coevolution, depending on the correlation between equilibrium state frequencies. We detected a striking excess of negative coevolution (corresponding to charge) at sites brought into proximity by the periodicity of the alpha-helix, and there was also a tendency for sites with significant likelihood ratios to be close in the three-dimensional structure. Sites on the surface of the protein appear to coevolve both when they are close in the structure, and when they are distant, implying a role for folding and/or avoidance of quaternary structure in the coevolution process.

Computer Simulation↗
PubMed1999

Evidence for mitochondrial DNA recombination in a human population of island Melanesia.

Mitochondrial DNA (mtDNA) analysis has proved useful in studies of recent human evolution and the genetic affinities of human groups of different geographical regions. As part of an extensive survey of mtDNA diversity in present-day Pacific populations, we obtained sequence information of the hypervariable mtDNA control region of 452 individuals from various localities in the western Pacific. The mtDNA types fell into three major groups which reflect the settlement history of the area. Interestingly, we detected an extremely rare point mutation at high frequency in the small island of Nguna in the Melanesian archipelago of Vanuatu. Phylogenetic analysis of the mtDNA data indicated that the mutation was present in individuals of separate mtDNA lineages. We propose that the multiple occurrence of a rare mutation event in one isolated locality is highly improbable, and that recombination between different mtDNA types is a more likely explanation for our observation. If correct, this conclusion has important implications for the use of mtDNA in phylogenetic and evolutionary studies.

Biological Evolution↗
PubMed1999

Beliefs about children's illness.

Beliefs about child illness were investigated using semi-structured interviews with mothers and providers in four rural Guatemalan communities. The two most common forms of child illness in Guatemala--diarrhoea and respiratory disease--were focused upon. These illnesses are particularly difficult to prevent and treat, especially with the rudimentary health services available in rural areas of developing countries. Comparisons with other ethnographic studies in Guatemala suggest that some traditional models of illness causation identified in these earlier investigations are relatively unimportant in the communities studied here. This finding, in conjunction with frequent responses related to hygiene and water, suggests that traditional explanations may be co-existing with biomedical views of illness causation to a greater degree today than in the past.

Child↗
PubMed1999

New insights into the Far Eastern pattern of mortality.

Some of the highest levels of excess mortality of males found anywhere in the world were present in several Far Eastern populations during the 1960s and 1970s but have progressively disappeared since that time. This study uses cause-of-death data to determine the diseases responsible for the existence and attenuation of these sex differences in Hong Kong, Singapore, and Taiwan. The results indicate that respiratory tuberculosis is the single most important underlying cause of the existence and attenuation of the pattern, that the role of liver diseases is not clear cut, and that other causes (such as cardiovascular diseases) are also important. A review of numerous risk factors yields no compelling reason why these populations experienced such large sex differences in mortality. However, it seems likely that public health and biomedical improvements (particularly those related to the reduction in mortality from tuberculosis) played a critical role in the attenuation of the Far Eastern mortality pattern.

Cause of Death↗