Biomedical subjects

N Goldman

Publications and source records attributed to N Goldman.

At least 37 records · Page 2Linked to original sources

PubMed1999

Can accurate data on birthweight be obtained from health interview surveys?

BACKGROUND: Because hospital records rarely exist for a representative sample of the population in developing countries, researchers frequently rely on birthweight data from surveys. Yet, the quality of these data has rarely been evaluated. This study explores the accuracy of birthweight information in six demographic and health surveys in Latin America conducted in the early 1990s: two in Guatemala, and one each in Bolivia, Costa Rica, El Salvador and Peru. METHODS: The quality of the birthweight reports is assessed by examining the plausibility of estimates of the proportion of newborns reported to have been weighed and estimates derived from the numerical weights, by characteristics of the delivery and maternal education. RESULTS: The estimates suggest that a substantial proportion of women whose newborns were probably never weighed report a birthweight. For all of the surveys, with the possible exception of Costa Rica, the average birthweights appear to be too high, and the estimates of the prevalence of low birthweight too low. In addition, the data reveal anomalous patterns, such as higher birthweights for home as compared with hospital deliveries. CONCLUSIONS: These findings suggest that estimates of low birthweight derived from surveys in developing countries are likely to portray an overly optimistic picture of children's and women's health status. More information about the underlying source of these data are needed not only to provide additional insight into the degree of error characterizing existing estimates, but also to improve data collection strategies in future health interview surveys.

Birth Weight↗

PubMed1999

Using protein structural information in evolutionary inference: transmembrane proteins.

We present a model of amino acid sequence evolution based on a hidden Markov model that extends to transmembrane proteins previous methods that incorporate protein structural information into phylogenetics. Our model aims to give a better understanding of processes of molecular evolution and to extract structural information from multiple alignments of transmembrane sequences and use such information to improve phylogenetic analyses. This should be of value in phylogenetic studies of transmembrane proteins: for example, mitochondrial proteins have acquired a special importance in phylogenetics and are mostly transmembrane proteins. The improvement in fit to example data sets of our new model relative to less complex models of amino acid sequence evolution is statistically tested. To further illustrate the potential utility of our method, phylogeny estimation is performed on primate CCR5 receptor sequences, sequences of l and m subunits of the light reaction center in purple bacteria, guinea pig sequences with respect to lagomorph and rodent sequences of calcitonin receptor and K-substance receptor, and cetacean sequences of cytochrome b.

Animals↗

PubMed1998

Phylogenetic information and experimental design in molecular systematics.

Despite the widespread perception that evolutionary inference from molecular sequences is a statistical problem, there has been very little attention paid to questions of experimental design. Previous consideration of this topic has led to little more than an empirical folklore regarding the choice of suitable genes for analysis, and to dispute over the best choice of taxa for inclusion in data sets. I introduce what I believe are new methods that permit the quantification of phylogenetic information in a sequence alignment. The methods use likelihood calculations based on Markov-process models of nucleotide substitution allied with phylogenetic trees, and allow a general approach to optimal experimental design. Two examples are given, illustrating realistic problems in experimental design in molecular phylogenetics and suggesting more general conclusions about the choice of genomic regions, sequence lengths and taxa for evolutionary studies.

Animals↗

PubMed1998

PASSML: combining evolutionary inference and protein secondary structure prediction.

MOTIVATION: Evolutionary models of amino acid sequences can be adapted to incorporate structure information; protein structure biologists can use phylogenetic relationships among species to improve prediction accuracy. Results : A computer program called PASSML ('Phylogeny and Secondary Structure using Maximum Likelihood') has been developed to implement an evolutionary model that combines protein secondary structure and amino acid replacement. The model is related to that of Dayhoff and co-workers, but we distinguish eight categories of structural environment: alpha helix, beta sheet, turn and coil, each further classified according to solvent accessibility, i.e. buried or exposed. The model of sequence evolution for each of the eight categories is a Markov process with discrete states in continuous time, and the organization of structure along protein sequences is described by a hidden Markov model. This paper describes the PASSML software and illustrates how it allows both the reconstruction of phylogenies and prediction of secondary structure from aligned amino acid sequences. AVAILABILITY: PASSML 'ANSI C' source code and the example data sets described here are available at http://ng-dec1.gen.cam.ac.uk/hmm/Passml.html and 'downstream' Web pages. CONTACT: P.Lio@gen.cam.ac.uk

Adenylate Kinase↗

PubMed1998

Assessing the impact of secondary structure and solvent accessibility on protein evolution.

Empirically derived models of amino acid replacement are employed to study the association between various physical features of proteins and evolution. The strengths of these associations are statistically evaluated by applying the models of protein evolution to 11 diverse sets of protein sequences. Parametric bootstrap tests indicate that the solvent accessibility status of a site has a particularly strong association with the process of amino acid replacement that it experiences. Significant association between secondary structure environment and the amino acid replacement process is also observed. Careful description of the length distribution of secondary structure elements and of the organization of secondary structure and solvent accessibility along a protein did not always significantly improve the fit of the evolutionary models to the data sets that were analyzed. As indicated by the strength of the association of both solvent accessibility and secondary structure with amino acid replacement, the process of protein evolution-both above and below the species level-will not be well understood until the physical constraints that affect protein evolution are identified and characterized.

Databases, Factual↗

PubMed1998

The use of calendars to measure child illness in health interview surveys.

BACKGROUND: During the past two decades, health interview surveys have become an increasingly common source of information about current morbidity patterns and utilization of health services in developing countries. This study describes a recent effort to enhance the utility of these surveys by incorporating a calendar format. METHODS: A calendar of morbidity and treatment behaviour during the 2-week period prior to interview was implemented in the Guatemalan Survey of Family Health (EGSF), a large-scale sample survey that was fielded in 60 communities in rural Guatemala in 1995. A total of 2872 women aged 18-35 were interviewed and provided information on 3193 children born since 1990. RESULTS: The EGSF calendar data provide estimates of diarrhoeal illness that are consistent with those obtained from more conventional questionnaire designs. However, in contrast to conventional health survey questions, these calendar data: (1) permit a much more complete evaluation of the accuracy of reporting; and (2) offer a richer and more complex description of child illness and treatment behaviour. For example, the results demonstrate that even the preferred 2-week recall period suffers from underreporting of diarrhoeal illness, that the majority of children with diarrhoea experience at least one additional symptom, and that mothers assess severity of diarrhoea from the type and number of accompanying symptoms. CONCLUSIONS: The findings indicate that additional implementation and evaluation of calendar formats is warranted in order to provide the most useful and accurate data possible at relatively low cost.

Adolescent↗

PubMed1998

Models of molecular evolution and phylogeny.

Phylogenetic reconstruction is a fast-growing field that is enriched by different statistical approaches and by findings and applications in a broad range of biological areas. Fundamental to these are the mathematical models used to describe the patterns of DNA base substitution and amino acid replacement. These may become some of the basic models for comparative genome research. We discuss these models, including the analysis of observed DNA base and amino acid mutation patterns, the concept of site heterogeneity, and the incorporation of structural biology data, all of which have become particularly important in recent years. We also describe the use of such models in phylogenetic reconstruction and statistical methods for the comparison of different models.

Amino Acid Substitution↗

PubMed1997

Misclassification bias in estimates of bereavement effects.

Prospective studies that examine marital status differences in health and mortality frequently fail to update information on marital status in statistical models. The authors illustrate how the resulting misclassification of marital status can produce substantial bias in estimates of bereavement effects associated with widowhood. They use as their main source of data the Longitudinal Study of Aging (LSOA), 1984-1990, a national survey of persons aged 70 years and older. The estimates are based primarily on 3,192 respondents who were married and cohabiting with their spouses at the time of the baseline survey and who could be matched to their spouses' records. Comparisons of widowhood status derived from matched spouse records with reported marital status recorded in LSOA interviews demonstrate that reliance on interview information leads to substantial misclassification of marital status. Results from survival models indicate that estimates of marital status effects are sensitive to whether and how marital status is updated after baseline interviews. For example, updating marital status in hazard models from interview information alone indicates a protective effect of widowhood, whereas classifying widowhood on the basis of spouses' death records reveals a significant bereavement effect (relative mortality risks between 1.3 and 1.4).

Aged↗

PubMed1997

Molecular characterization and ultrastructural localization of Plasmodium falciparum Hsp 60.

Heat shock proteins (Hsp) are a group of highly conserved proteins which are widely represented phylogenetically. Genes for members of the Hsp 70, 90 and 60 families have been cloned from the human malaria parasite Plasmodium falciparum. In this study, we have cloned and expressed the P. falciparum Hsp 60 (PfHsp60) in E. coli. The sequence analysis identified a previously unknown intron of 257 bp beginning after the nucleotide 142 in the coding sequence. Antisera raised against the recombinant PfHsp60 was employed in immunoprecipitation studies with biosynthetically labeled parasite extracts to investigate regulation of expression of PfHsp60 at various temperatures. In contrast to the three to four fold accumulation of PfHsp60 transcripts in heat shocked parasites (37-40 degrees C), the expression of PfHsp60 was not induced in the blood stages of P. falciparum. On the other hand, the effect of heat induction on PfHsp70 was seen both at the level of specific mRNA and protein. In these studies we also observed co-immunoprecipitation of a number of other cellular proteins suggesting possible interaction with PfHsp60. Immunofluorescence analysis indicated the presence of PfHsp60 in the cytoplasm of all the various stages of the parasite. In addition, immunoelectron microscopic analysis distinctly localized PfHsp60 in the mitochondrion of P. falciparum. This study suggests that different mechanisms are involved in the regulation of expression of various members of the heat shock proteins in the parasite.

Animals↗

PubMed1997

Antibody response to influenza immunization in patients after heart transplantation.

The aim of this study was to evaluate post-heart transplantation (Htx) response to two-dose and three-dose influenza vaccine. Hemagglutination inhibition antibodies were monitored in HTx recipients immunized twice (n = 25) or three times (n = 17), and non-HTx controls (n = 8) once, with inactivated influenza vaccine. Post-first dose protective antibody titers (> or = 1:40) were demonstrated in 9/25 (36%) for A/Singapore/ (H1N1), 5/25 (20%) for A/Shanghai/(H3N2) and 2/25 (8%) for B/Yamagata compared with 4/8 (50%), 6/8 (75%) and 2/8 (25%), respectively, for controls. Post-second dose protective titers remained low, increasing following the third dose to 71%, 65% and 29%, respectively. The abnormally low antibody responses of HTx recipients to one-dose and two-dose influenza vaccine can be overcome by a third dose.

Adolescent↗

PubMed1997

The treatment of relapsed or refractory intermediate grade non-Hodgkin's lymphoma with autologous bone marrow transplantation followed by cyclosporine and interferon.

In an effort to decrease the relapse rate following autologous bone marrow transplantation for non-Hodgkin's lymphoma, patients were given cyclosporine and interferon following autologous marrow transplantation. Forty patients with intermediate grade non-Hodgkin's lymphoma that was relapsed or refractory to standard chemotherapy underwent autologous marrow transplantation. The preparative regimen consisted of cyclophosphamide 6.8 g/m2, etoposide 1600 mg/m2, and carmustine 400 mg/m2 over 4 days followed by reinfusion of bone marrow. Intravenous cyclosporine was started on day -1 as a 16 mg/kg loading dose followed by 3.6 mg/kg/day for 28 days after transplant. Patients were begun on alpha-interferon (starting dose, 0.5 million units s.c. every other day) following platelet engraftment (median day 24 post-transplant) and continued on 1.5 million units s.c. daily for 2 years. Regimen-related toxicities resulted in four (10%) deaths. Twenty-one (53%) patients developed marked erythema of the palms, soles, and arms. Biopsies of the erythema were consistent with grade I GVHD. Patients who did not develop rashes were not biopsied. The erythema persisted for a median of 10 days and resolved in all cases without treatment. Visceral GVHD was not apparent. All patients have been followed for a median of 24 months (range 12-54 months). To date, only five patients (13%) have relapsed after bone marrow transplant. Multivariant analysis could not identify risk factors for relapse post-transplant. Disease-free survival of all patients is 77% (95% confidence interval, 67-93%). The results of this pilot study suggest that the administration of cyclosporine and interferon may decrease the relapse rate of relapsed/refractory non-Hodgkin's lymphoma following autologous bone marrow transplantation.

Adolescent↗

PubMed1996

Using evolutionary trees in protein secondary structure prediction and other comparative sequence analyses.

Previously proposed methods for protein secondary structure prediction from multiple sequence alignments do not efficiently extract the evolutionary information that these alignments contain. The predictions of these methods are less accurate than they could be, because of their failure to consider explicitly the phylogenetic tree that relates aligned protein sequences. As an alternative, we present a hidden Markov model approach to secondary structure prediction that more fully uses the evolutionary information contained in protein sequence alignments. A representative example is presented, and three experiments are performed that illustrate how the appropriate representation of evolutionary relatedness can improve inferences. We explain why similar improvement can be expected in other secondary structure prediction methods and indeed any comparative sequence analysis method.

Amino Acid Sequence↗

PubMed1996

Combining protein evolution and secondary structure.

An evolutionary model that combines protein secondary structure and amino acid replacement is introduced. It allows likelihood analysis of aligned protein sequences and does not require the underlying secondary (or tertiary) structures of these sequences to be known. One component of the model describes the organization of secondary structure along a protein sequence and another specifies the evolutionary process for each category of secondary structure. A database of proteins with known secondary structures is used to estimate model parameters representing these two components. Phylogeny, the third component of the model, can be estimated from the data set of interest. As an example, we employ our model to analyze a set of sucrose synthase sequences. For the evolution of sucrose synthase, a parametric bootstrap approach indicates that our model is statistically preferable to one that ignores secondary structure.

Amino Acid Sequence↗

PubMed1996

Prenatal and delivery care and childhood immunization in Guatemala: do family and community matter?

In this paper we investigate family choices about pregnancy-related care and the use of childhood immunization. Estimates obtained from a multilevel logistic model indicate that use of formal (or "modern") health services differs substantially by ethnicity, by social and economic factors, and by availability of health services. The results also show that family and community membership are very important determinants of the use of health care, even in the presence of controls for a large number of observed characteristics of individuals, families, and communities.

Child, Preschool↗

PubMed1995

Marital status and health among the elderly.

Many studies have documented a longevity advantage for married persons relative to their unmarried counterparts in all age groups. However, these studies have failed to determine whether the advantage experienced by married elderly persons arises mostly from selection and causal processes which operated at younger ages. This paper employs data from the Longitudinal Study of Aging (1984-1990) to explore whether marital status continues to exert any influence on health and mortality at the older ages. In the presence of an extensive set of controls for health status at the baseline survey, a series of logistic models are used to determine: (1) the magnitude of marital status effects on disability and on mortality, among older males and older females; and (2) the extent to which the social environment and economic status of the elderly can account for the existing disability and mortality differences by marital status.

Activities of Daily Living↗

PubMed1995

Human immunodeficiency virus type 2 (HIV-2) env gene analysis: prediction of glycoprotein epitopes important for heterotypic neutralization and evidence for three genotype clusters within the HIV-2a subtype.

The env gene sequences of ten tissue-culture-adapted human immunodeficiency virus type 2 (HIV-2) isolates from West African patients were determined. Alignment and comparison of the gene sequences and putative translation products with database sequences revealed 11-29% diversity at the nucleotide level and 15-31% variation at the protein level. From analysis of glycoproteins of HIV-2 strains sensitive and resistant to neutralization by HIV-1 antisera, five regions were identified as putative targets for cross-neutralizing antibody. The HIV-2 equivalent of the HIV-1 V3 loop was not included in this number. However, three of the HIV-2 peptides aligned with regions identified as targets for broad neutralization of HIV-1 strains. These were the V2 and CD4-binding domains of gp120 and the Kennedy domain in gp41. Phylogenetic analysis of the env gene sequences, together with HIV-2 env gene sequences published in the Los Alamos database, support the identification of two distinct HIV-2 subtypes, HIV-2a and HIV-2b. The new sequences are located within the HIV-2a subtype and allow prediction of at least three genotypes, designated I-III. Some correlation of genotype with geographical origin of isolates was noted. Genotype I viruses originate from Guinea Bissau and group II viruses mainly originate from The Gambia. One isolate from Guinea Bissau, HIV-2CAM4, appears phylogenetically older than other viruses in the HIV-2a subtype. The possible implications of this in the light of epidemiological findings in Guinea Bissau are discussed.

Amino Acid Sequence↗

PubMed1995

Social inequality and children's growth in Guatemala.

This paper is an investigation of the effects of social inequality in Guatemala on children's health and nutritional status as measured by attained height. Guatemala remains a highly stratified and poor society. We examine the association of land distribution, land tenure, occupation, and other aspects of family social and economic status with children's height between the ages of three months and 36 months, using data from a cross-sectional survey. An important consequence of the poverty and poor living conditions of the majority of the Guatemalan population is substantial deficits in children's growth. Our results suggest that children's growth is affected by ethnicity, their father's occupation, land distribution in the area where they live, and maternal education. Substantial growth deficits are observed among children living at altitudes above 1500 metres; we hypothesize that this is because, in Guatemala, higher altitude is associated with land scarcity, poorer agricultural conditions, and greater remoteness from transport networks and other public services.

Adolescent↗

PubMed1994

Social factors and health: the causation-selection issue revisited.

Since social scientists rarely have access to experimental data, they rely heavily upon observational studies. As a consequence, their attempts to make causal inferences about the effects of social factors--such as occupation or marital status--on health are plagued by potential selection problems. Some researchers have addressed this selection-causation problem on the basis of the presence or absence of a particular aggregate pattern of health status. The rationale underlying this approach derives from the investigators' hypotheses that the presence of selection would lead to a particular type of pattern that is distinct from the pattern that would result in the absence of selection. Although intuitively appealing, this strategy appears to be seriously flawed. The essential weakness is that the range of patterns that can result from selection is often much broader than researchers have speculated.

Causality↗