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Biomedical subjects

Robert E Weiss

Publications and source records attributed to Robert E Weiss.

At least 19 recordsLinked to original sources

HIV-1 viral fitness estimation using exchangeable on subsets priors and prior model selection.

The phenotype-genotype problem is a fundamental problem of biology where an organism's genotype (genetic information) predicts its phenotype (observable characteristic). Viral fitness, defined as the reproductive capacity of a virus compared to a standard, is a continuous phenotype. We construct models to predict viral fitness as a function of mutation away from the standard wildtype virus. Data of this nature are difficult to analyse because there are potentially many more parameters than observations. We treat this issue as a regression problem using a prior with both a shrinkage component and a variable selection component. The key to practical implementation of the model is the prior specification for the regression coefficients. We use results from the scientific literature to construct several informative exchangeable within subsets priors (ESP). We use prior model selection (PMS) to select among our priors. Two novel graphics present results from five models each with 71 predictors.

Codon↗

Time squared: repeated measures on phylogenies.

Studies of gene expression profiles in response to external perturbation generate repeated measures data that generally follow nonlinear curves. To explore the evolution of such profiles across a gene family, we introduce phylogenetic repeated measures (PR) models. These models draw strength from 2 forms of correlation in the data. Through gene duplication, the family's evolutionary relatedness induces the first form. The second is the correlation across time points within taxonic units, individual genes in this example. We borrow a Brownian diffusion process along a given phylogenetic tree to account for the relatedness and co-opt a repeated measures framework to model the latter. Through simulation studies, we demonstrate that repeated measures models outperform the previously available approaches that consider the longitudinal observations or their differences as independent and identically distributed by using deviance information criteria as Bayesian model selection tools; PR models that borrow phylogenetic information also perform better than nonphylogenetic repeated measures models when appropriate. We then analyze the evolution of gene expression in the yeast kinase family using splines to estimate nonlinear behavior across 3 perturbation experiments. Again, the PR models outperform previous approaches and afford the prediction of ancestral expression profiles. To demonstrate PR model applicability more generally, we conclude with a short examination of variation in brain development across 4 primate species.

Algorithms↗

Newly homeless youth STD testing patterns over time.

PURPOSE: To use the Behavioral Model for Vulnerable Populations to examine the predisposing and need characteristics of newly homeless youth that are associated with sexually transmitted disease (STD) testing over time. METHODS: A longitudinal cohort of newly homeless youth from Los Angeles County (n = 261; ages 12-20 years) were followed for 24 months. Youth were interviewed at baseline, 3, 6, 12, 18, and 24 months, and asked about their background, housing situation, emotional distress (using the Brief-Symptom Inventory), substance use, sexual risk behaviors, and their STD testing rates. We modeled our longitudinal data using logistic random effects models. RESULTS: Characteristics of homeless youth that were associated with STD testing in our multivariate model included time in study (odds ratio [OR] 1.3, 95% confidence interval [CI] 1.1-1.6), age at baseline (OR 1.2, 95% CI 1.1-1.4), being African-American (OR 2.7, 95% CI 1.4-5.3), being from a mixed race/ethnic group (OR 2.8, 95% CI 1.3-5.8), self-identifying as a gay/bisexual male (OR 2.9, 95% CI 1.2-6.9), self-identifying as a heterosexual female (OR 2.2, 95% CI 1.3-3.7), using amphetamines (OR 1.7, 95% CI 1.1-2.6), and history of having gotten someone/becoming pregnant (OR 2.3, 95% CI 1.4-3.9). Youth who lived in an apartment were less likely to have received an STD test than youth who lived in other types of housing (OR .4, 95% CI .2-.9). Sexual risk behaviors such as inconsistent condom use (OR 1.0, 95% CI .6-1.4) and number of sexual partners over past 3 months (OR 1.1, 95% CI 1.0-1.1) were not predictive of STD testing over time. CONCLUSIONS: A need exists for interventions to target young newly homeless youth who engage in high-risk sexual behaviors to increase their STD testing rates and thereby decrease their risk for HIV infection.

Adolescent↗

A Bayesian heterogeneous analysis of variance approach to inferring recent selective sweeps.

The distribution of microsatellite allele sizes in populations aids in understanding the genetic diversity of species and the evolutionary history of recent selective sweeps. We propose a heterogeneous Bayesian analysis of variance model for inferring loci involved in recent selective sweeps by analyzing the distribution of allele sizes at multiple loci in multiple populations. Our model is shown to be consistent with a multilocus test statistic, ln RV, proposed for identifying microsatellite loci involved in recent selective sweeps. Our methodology differs in that it accepts original allele size data rather than summary statistics and allows the incorporation of prior knowledge about allele frequencies using a hierarchical prior distribution consisting of log normal and gamma probability distributions. Interesting features of the model are its ability to simultaneously analyze allele size data for any number of populations and to cope with the presence of any number of selected loci. The utility of the method is illustrated by application to two sets of microsatellite allele size data for a group of West African Anopheles gambiae populations. The results are consistent with the suppressed-recombination model of speciation, and additional candidate loci on chromosomes 2 (079 and 175) and 3 (088) are discovered that escaped former analysis.

Alleles↗

Intake of micronutrients high in animal-source foods is associated with better growth in rural Kenyan school children.

Observational studies have shown that children in developing countries consuming diets containing high amounts of bioavailable nutrients, such as those found in animal-source foods, grow better. The present study investigated which specific nutrients from the diet of Kenyan school children predicted their growth. The children (n 544, median age 7 years) participated in a 2-year long food supplementation study with animal-source foods. Height gain during the intervention period was positively predicted by average daily intakes of energy from animal-source foods, haem Fe, preformed vitamin A, Ca and vitamin B12. Weight gain was positively predicted by average daily intakes of energy from animal-source foods, haem Fe, preformed vitamin A, Ca and vitamin B12. Gain in mid-upper-arm muscle area was positively predicted by average daily intakes of energy from animal-source foods and vitamin B12. Gain in mid-upper-arm fat area was positively predicted by average daily intakes of energy from animal-source foods. Gain in subscapular skinfold thickness was not predicted by any of the nutrient intakes. Negative predictors of growth were total energy and nutrients that are contained in high amounts in plant foods. The study shows that growth was positively predicted by energy and nutrients that are provided in high amounts and in a bioavailable form in meat and milk, and their inclusion into the diets of children in developing countries should be part of all food-based programmes in order to improve micronutrient status and growth.

Adipose Tissue↗

Changing behaviors and patterns among Cambodian sex workers: 1997-2003.

OBJECTIVE: Identify patterns and behaviors among direct and indirect female sex workers (DFSWs and IDFSWs, respectively) across Cambodia's 5 major cities from 1997 to 2003. METHODS: Interviews with DFSWs and IDFSWs followed random selection from clusters in 5 cities. Individual characteristics and condom use with clients and other partners were assessed in univariate and multivariate analyses. RESULTS: From 1997 to 2003, consistent condom use with clients increased from 53% to 96% among DFSWs and from 30% to 84% among IDFSWs. DFSWs reported staying in their profession longer, had fewer clients per day, stayed longer in each brothel, were in increasingly larger brothels, and were tested more for HIV. For IDFSWs, there were significant changes: more reported practicing commercial sex and testing for HIV. In adjusted models, reported condom use with clients was significantly higher among DFSWs in later survey years (odds ratio [OR], 2.17) and who were never married (OR, 1.69), were in larger brothels (OR, 1.02), and charged more for sex (OR, 1.27), but lower for DFSWs with sweethearts (OR, 0.68) and who reported abnormal vaginal discharge (OR, 0.52). For IDFSWs, in the adjusted models, reported condom use with clients was higher in later years (OR, 1.77) and for those reporting abnormal vaginal discharge (OR, 1.34) and HIV testing (OR, 1.46), and lower for those with sweethearts (OR, 0.49). CONCLUSIONS: From 1997 to 2003, Cambodian direct and indirect sex workers increased their use of condoms each year with commercial as well as noncommercial partners, contributing to the evidence that HIV prevention programs can produce significant changes in risk behaviors.

Adult↗

Models for estimating bayes factors with applications to phylogeny and tests of monophyly.

Bayes factors comparing two or more competing hypotheses are often estimated by constructing a Markov chain Monte Carlo (MCMC) sampler to explore the joint space of the hypotheses. To obtain efficient Bayes factor estimates, Carlin and Chib (1995, Journal of the Royal Statistical Society, Series B57, 473-484) suggest adjusting the prior odds of the competing hypotheses so that the posterior odds are approximately one, then estimating the Bayes factor by simple division. A byproduct is that one often produces several independent MCMC chains, only one of which is actually used for estimation. We extend this approach to incorporate output from multiple chains by proposing three statistical models. The first assumes independent sampler draws and models the hypothesis indicator function using logistic regression for various choices of the prior odds. The two more complex models relax the independence assumption by allowing for higher-lag dependence within the MCMC output. These models allow us to estimate the uncertainty in our Bayes factor calculation and to fully use several different MCMC chains even when the prior odds of the hypotheses vary from chain to chain. We apply these methods to calculate Bayes factors for tests of monophyly in two phylogenetic examples. The first example explores the relationship of an unknown pathogen to a set of known pathogens. Identification of the unknown's monophyletic relationship may affect antibiotic choice in a clinical setting. The second example focuses on HIV recombination detection. For potential clinical application, these types of analyses must be completed as efficiently as possible.

Bayes Theorem↗

Diet quality affects the playground activities of Kenyan children.

The present study examined the effects of a school breakfast program on the activity level, emotional state, and social interactions of a group of Kenyan schoolchildren on the playground. Five hundred forty children in rural Kenya participated in the study. The first standard (grade) classes were randomly assigned to groups provided for 21 months with school breakfasts of equivalent caloric value while families with children in the control group were given a goat at the end of the study. The study aimed to determine whether enhanced caloric intake or diet quality influenced the children's behavior on the school playground. The results indicate that supplemented children were more active and showed more leadership behavior and initiative than did non-supplemented children. In addition, children given meat showed fewer periods of low activity and more leadership behaviors and initiative than did children provided entirely with vegetable source foods. These results support our previous findings from naturalistic studies in the same community that both diet quantity and quality are important for children's development.

Animals↗

Prevention for substance-using HIV-positive young people: telephone and in-person delivery.

SUMMARY: HIV risky behaviors and health practices were examined among young people living with HIV (YPLH) in Los Angeles, San Francisco, and New York over 15 months in response to receiving a preventive intervention. YPLH aged 16 to 29 years (n = 175; 26% black and 42% Latino; 69% gay men) were randomly assigned to a 3-module intervention totaling 18 sessions delivered by telephone, in person, or a delayed-intervention condition. Intention-to-treat analyses found that the in-person intervention resulted in a significantly higher proportion of sexual acts protected by condoms overall and with HIV-seronegative partners. Pre- and postanalyses of YPLH in the delayed-intervention condition alone found that YPLH tended to have fewer sexual partners, used fewer drugs, reported less emotional distress, and decreased their use of antiretroviral therapies. Prevention programs can be delivered in alternative formats while retaining efficacy. When YPLH are using hard drugs, drug treatment may be needed before delivery of preventive interventions.

Adolescent↗

Routine pouchograms are not necessary after continent urinary diversion.

OBJECTIVES: Pouchograms are routinely performed before catheter removal after continent urinary diversion at our institution. Our aim was to determine the necessity of pouchograms based on a review of our experience. METHODS: A retrospective review of patient records and radiographic studies was done for patients undergoing radical cystectomy and continent urinary diversions between 1991 and 2001. RESULTS: Seventy-two patients underwent continent urinary diversion (orthotopic, n = 59; cutaneous, n = 13) during the study period. All underwent pouchogram postoperatively (median 22 days; range 20 to 27). Six patients (8.3%) had a demonstrable radiographic leak; in 5 of the 6 patients, the urine leak was suspected on clinical grounds. Three patients (4.7%) developed urosepsis after pouchogram. CONCLUSIONS: Our findings indicate that routine pouchograms before pouch activation after continent urinary diversion may not be necessary.

Adult↗

Correlates of sex trading among drug-using men who have sex with men.

OBJECTIVES: We examined correlates of trading sex for money, drugs, and shelter, or food among drug-using men who have sex with men (MSM). METHODS: Audio computer-assisted self-interviewing questionnaires were completed by 387 MSM. The association of predictors with sex trading was assessed with chi(2) tests and multiple logistic regression. RESULTS: Sex-trading prevalence was 62.5% (95% confidence interval=57.7%, 67.4%). Sex trading was associated with crack use, injection drug use, childhood maltreatment, non-gay self-identification, and homelessness (adjusted odds ratios=3.72, 2.28, 2.62, 2.21, and 1.88, respectively). CONCLUSIONS: Multiple risk factors are associated with sex trading among MSM. Interventions may need to address crack and injection drug use, homelessness, and childhood maltreatment and target non-gay-identified MSM who engage in sex trading.

Adolescent↗

Testing a molecular clock without an outgroup: derivations of induced priors on branch-length restrictions in a Bayesian framework.

We propose a Bayesian method for testing molecular clock hypotheses for use with aligned sequence data from multiple taxa. Our method utilizes a nonreversible nucleotide substitution model to avoid the necessity of specifying either a known tree relating the taxa or an outgroup for rooting the tree. We employ reversible jump Markov chain Monte Carlo to sample from the posterior distribution of the phylogenetic model parameters and conduct hypothesis testing using Bayes factors, the ratio of the posterior to prior odds of competing models. Here, the Bayes factors reflect the relative support of the sequence data for equal rates of evolutionary change between taxa versus unequal rates, averaged over all possible phylogenetic parameters, including the tree and root position. As the molecular clock model is a restriction of the more general unequal rates model, we use the Savage-Dickey ratio to estimate the Bayes factors. The Savage-Dickey ratio provides a convenient approach to calculating Bayes factors in favor of sharp hypotheses. Critical to calculating the Savage-Dickey ratio is a determination of the prior induced on the modeling restrictions. We demonstrate our method on a well-studied mtDNA sequence data set consisting of nine primates. We find strong support against a global molecular clock, but do find support for a local clock among the anthropoids. We provide mathematical derivations of the induced priors on branch length restrictions assuming equally likely trees. These derivations also have more general applicability to the examination of prior assumptions in Bayesian phylogenetics.

Animals↗

Hierarchical phylogenetic models for analyzing multipartite sequence data.

Debate exists over how to incorporate information from multipartite sequence data in phylogenetic analyses. Strict combined-data approaches argue for concatenation of all partitions and estimation of one evolutionary history, maximizing the explanatory power of the data. Consensus/independence approaches endorse a two-step procedure where partitions are analyzed independently and then a consensus is determined from the multiple results. Mixtures across the model space of a strict combined-data approach and a priori independent parameters are popular methods to integrate these methods. We propose an alternative middle ground by constructing a Bayesian hierarchical phylogenetic model. Our hierarchical framework enables researchers to pool information across data partitions to improve estimate precision in individual partitions while permitting estimation and testing of tendencies in across-partition quantities. Such across-partition quantities include the distribution from which individual topologies relating the sequences within a partition are drawn. We propose standard hierarchical priors on continuous evolutionary parameters across partitions, while the structure on topologies varies depending on the research problem. We illustrate our model with three examples. We first explore the evolutionary history of the guinea pig (Cavia porcellus) using alignments of 13 mitochondrial genes. The hierarchical model returns substantially more precise continuous parameter estimates than an independent parameter approach without losing the salient features of the data. Second, we analyze the frequency of horizontal gene transfer using 50 prokaryotic genes. We assume an unknown species-level topology and allow individual gene topologies to differ from this with a small estimable probability. Simultaneously inferring the species and individual gene topologies returns a transfer frequency of 17%. We also examine HIV sequences longitudinally sampled from HIV+ patients. We ask whether posttreatment development of CCR5 coreceptor virus represents concerted evolution from middisease CXCR4 virus or reemergence of initial infecting CCR5 virus. The hierarchical model pools partitions from multiple unrelated patients by assuming that the topology for each patient is drawn from a multinomial distribution with unknown probabilities. Preliminary results suggest evolution and not reemergence.

Animals↗

Animal source foods improve dietary quality, micronutrient status, growth and cognitive function in Kenyan school children: background, study design and baseline findings.

A previous longitudinal three-country study in Egypt, Kenya and Mexico found significant positive associations between intake of animal source foods (ASF) and growth, cognitive development and physical activity. To test for a causal relationship, a controlled school feeding intervention study was designed to test the hypotheses that ASF would improve micronutrient status, growth and cognitive function in Kenyan primary school children. Twelve rural Kenyan schools with 554 children were randomized to four feeding interventions using a local vegetable stew as the vehicle. The groups were designated as Meat, Milk, Energy and Control, who received no feedings. Feeding was carried out on school days for seven terms during 21 mo. Preintervention baseline measures included nutritional status, home food intake, anthropometry, biochemical measures of micronutrient status, malaria, intestinal parasites, health status and cognitive and behavioral measures. The measurements of each child were repeated at intervals over 2 y. Baseline data revealed stunting and underweight in approximately 30% of children and widespread inadequate intakes and/or biochemical evidence of micronutrient deficiencies, particularly of iron, zinc, vitamins A and B-12, riboflavin and calcium. Little or no ASF were eaten and fat intake was low. Malaria was present in 31% of children, and hookworm, amebiasis and giardia were widely prevalent. The outcomes measured were rates of change or increase during the intervention in cognitive function, growth, physical activity and behavior and micronutrient status. Hierarchical linear random effects modeling was used for analysis of outcomes.

Animals↗

The impact of dietary intervention on the cognitive development of Kenyan school children.

Previous observational studies in developing countries have suggested that diet quality, particularly increased animal source food (ASF) consumption, is positively associated with child cognitive development. This report presents findings from a study in rural Kenya, designed to test the impact of three different diets on the cognitive development of school children. Twelve schools with a total of 555 Standard 1 children (equivalent to U.S. Grade 1) were randomized to one of four feeding interventions: Meat, Milk, Energy or Control (no feeding). Feeding continued for seven school terms (21 mo), and cognitive tests were administered before the commencement of feeding and during every other term of feeding. Hierarchical linear random effects models and associated methods were used to examine the effects of treatment group on changes in cognitive performance over time. Analyses revealed that children receiving supplemental food with meat significantly outperformed all other children on the Raven's Progressive Matrices. Children supplemented with meat, and children supplemented with energy, outperformed children in the Control group on tests of arithmetic ability. There were no group differences on tests of verbal comprehension. Results suggest that supplementation with animal source food has positive effects on Kenyan children's cognitive performance. However, these effects are not equivalent across all domains of cognitive functioning, nor did different forms of animal source foods produce the same beneficial effects. Implications of these findings for supplementation programs in developing countries are discussed.

Animals↗

Are you my mother? Bayesian phylogenetic inference of recombination among putative parental strains.

Reconstructing evolutionary relationships using Bayesian inference has become increasingly popular due to the ability of Bayesian inference to handle complex models of evolution. In this review we concentrate on inference of recombination events between strains of viruses when these events are sporadic, ie rare relative to point mutations. Bayesian inference is especially attractive in the detection of recombination events because it allows for simultaneous inferences about the presence, number and location of crossover points and the identification of parental sequences. Current frequentist recombination identification falls into a sequential testing trap. The most likely parental sequences and crossover points are identified using the data and then the certainty of recombination is assessed conditional on this identification. After briefly outlining basic phylogenetic models, Bayesian inference and Markov chain Monte Carlo (MCMC) computation, we summarise three different approaches to recombination detection and discuss current challenges in applying Bayesian phylogenetic inference of recombination.

Algorithms↗

Implications of radioactive seed migration to the lungs after prostate brachytherapy.

OBJECTIVES: To review the incidence and the impact of pulmonary seed migration after prostate brachytherapy on lung function. Isolated reports of seed migration to the lungs after prostate brachytherapy have been published; however, the clinical consequences of this pulmonary migration have not been adequately evaluated. METHODS: We performed a retrospective review of patients undergoing prostate brachytherapy from 1998 to 2000. Pulmonary imaging with chest x-ray was performed 15 to 90 days (median 45) after the procedure. The chest radiographs were reviewed by a single radiologist (V.S.D.), and patients with seed migration to the lungs were evaluated by a single pulmonologist (A.M.H.) using a questionnaire, chest radiography, and pulmonary function tests. Computed tomography of the prostate after seed implantation was performed to check seed position and dosimetry. Odds ratio, confidence intervals, chi-square tests, and logistic regression analysis were performed to evaluate the relationship between the type and number of seeds used, the incidence of pulmonary migration, and the effects on pulmonary function. RESULTS: A total of 83 patients underwent prostate brachytherapy during the study period and 58 patients underwent chest radiography. Seed migration occurred in 21 (36.2%) of 58 patients (95% confidence interval 23.8% to 48.6%). Thirty-four (0.71%) of 4755 seeds used migrated to the lungs. Nine patients had single seed migration to the right lung and three to the left lung. Nine patients had multiple (maximum of 4) and bilateral seed migration. No consistent relationship was found between seed migration and the type of seeds used (P = 0.24). Borderline statistical significance suggested an increased incidence of seed migration with an increasing number of implanted seeds (P = 0.054). Repeat chest radiography in 21 patients revealed no delayed migration at a median follow-up of 16 months. Clinical and pulmonary function testing revealed no consistent abnormality attributable to seed migration. CONCLUSIONS: Radioactive seed migration occurred in 36.2% of brachytherapy patients who had chest radiographs done in our series. Pulmonary seed migration may be influenced by the number of implanted seeds and does not appear to be influenced by the seed type. Additional study of this observed phenomenon is required. A thorough pulmonary workup failed to reveal any short-term harmful side effects; however, long-term follow-up is needed. Healthcare providers should discuss the possibility of pulmonary seed migration with patients with prostate cancer considering prostate brachytherapy.

Brachytherapy↗

Villous adenoma of the urinary tract: a lesion frequently associated with malignancy.

Villous adenomas arising in the urinary tract are rare. We identified 18 cases of villous adenomas of the bladder, urachus, and prostatic urethra. Patients ranged in age from 53 to 93 years with an average age of 69.6 years and a male preponderance of 67%. In six cases (33%), the lesion was pure villous adenoma. In three cases (17%), there was villous adenoma with in situ adenocarcinoma. In six cases (33%) there was villous adenoma with in situ and infiltrating adenocarcinoma. One case (6%) had villous adenomas with in situ (noninvasive) papillary urothelial carcinoma. One case (6%) had villous adenomas with in situ adenocarcinoma and in situ papillary (noninvasive) and infiltrating urothelial carcinoma. The remaining case (6%) had villous adenoma with in situ and infiltrating adenocarcinoma and in situ (noninvasive) papillary and infiltrating urothelial carcinoma. Clinical outcome was available in eight of the cases, with a mean follow-up of 4.6 years. No evidence of recurrence was found in two patients with pure villous adenoma or in two patients with villous adenoma and only in situ adenocarcinoma, all of whom were treated by nonradical excision. However, two of three cases with infiltrating cancer developed distant metastases despite radical surgery; the remaining patient was disease-free 11 years after transurethral resection. The case with villous adenoma and in situ urothelial carcinoma progressed to sarcomatoid urothelial carcinoma following partial cystectomy. Eight of 10 villous adenomas cases studied expressed the epitope for mAbDas1, found on colonic epithelium and primary adenocarcinomas of the bladder and urachus but not on normal or neoplastic urothelium. This study expands the spectrum of histologic features accompanying villous adenomas of the urinary tract. Coexisting infiltrating adenocarcinoma is often present, necessitating thorough sampling of any lesion diagnosed by biopsy as villous adenoma. Pure villous adenoma and those well-sampled lesions also containing in situ adenocarcinoma portend a favorable prognosis, even without radical treatment. Coexisting in situ or infiltrating carcinoma suggests a more aggressive course. Histologically, immunohistochemically, and prognostically, these lesions appear analogous to their counterparts in the intestine.

Adenocarcinoma↗