Biomedical subjects

Michael J Daniels

Publications and source records attributed to Michael J Daniels.

12 recordsLinked to original sources

PubMed2006

On estimation of vaccine efficacy using validation samples with selection bias.

Using validation sets for outcomes can greatly improve the estimation of vaccine efficacy (VE) in the field (Halloran and Longini, 2001; Halloran and others, 2003). Most statistical methods for using validation sets rely on the assumption that outcomes on those with no cultures are missing at random (MAR). However, often the validation sets will not be chosen at random. For example, confirmational cultures are often done on people with influenza-like illness as part of routine influenza surveillance. VE estimates based on such non-MAR validation sets could be biased. Here we propose frequentist and Bayesian approaches for estimating VE in the presence of validation bias. Our work builds on the ideas of Rotnitzky and others (1998, 2001), Scharfstein and others (1999, 2003), and Robins and others (2000). Our methods require expert opinion about the nature of the validation selection bias. In a re-analysis of an influenza vaccine study, we found, using the beliefs of a flu expert, that within any plausible range of selection bias the VE estimate based on the validation sets is much higher than the point estimate using just the non-specific case definition. Our approach is generally applicable to studies with missing binary outcomes with categorical covariates.

Adolescent↗

PubMed2006

Effects of variation in protein and carbohydrate intake on body mass and composition during energy restriction: a meta-regression 1.

BACKGROUND: It is unclear whether low-carbohydrate, high-protein, weight-loss diets benefit body mass and composition beyond energy restriction alone. OBJECTIVE: The objective was to use meta-regression to determine the effects of variations in protein and carbohydrate intakes on body mass and composition during energy restriction. DESIGN: English-language studies with a dietary intervention of > or =4200 kJ/d (1000 kcal/d), with a duration of > or =4 wk, and conducted in subjects aged > or =19 y were considered eligible for inclusion. A self-reported intake in conjunction with a biological marker of macronutrient intake was required as a minimum level of dietary control. A total of 87 studies comprising 165 intervention groups met the inclusion criteria. RESULTS: After control for energy intake, diets consisting of < or =35-41.4% energy from carbohydrate were associated with a 1.74 kg greater loss of body mass, a 0.69 kg greater loss of fat-free mass, a 1.29% greater loss in percentage body fat, and a 2.05 kg greater loss of fat mass than were diets with a higher percentage of energy from carbohydrate. In studies that were conducted for >12 wk, these differences increased to 6.56 kg, 1.74 kg, 3.55%, and 5.57 kg, respectively. Protein intakes of >1.05 g/kg were associated with 0.60 kg additional fat-free mass retention compared with diets with protein intakes < or =1.05 g/kg. In studies conducted for >12 wk, this difference increased to 1.21 kg. No significant effects of protein intake on loss of either body mass or fat mass were observed. CONCLUSION: Low-carbohydrate, high-protein diets favorably affect body mass and composition independent of energy intake, which in part supports the proposed metabolic advantage of these diets.

Adipose Tissue↗

PubMed2005

Longitudinal profiling of health care units based on continuous and discrete patient outcomes.

Monitoring health care quality involves combining continuous and discrete outcomes measured on subjects across health care units over time. This article describes a Bayesian approach to jointly modeling multilevel multidimensional continuous and discrete outcomes with serial dependence. The overall goal is to characterize trajectories of traits of each unit. Underlying normal regression models for each outcome are used and dependence among different outcomes is induced through latent variables. Serial dependence is accommodated through modeling the pairwise correlations of the latent variables. Methods are illustrated to assess trends in quality of health care units using continuous and discrete outcomes from a sample of adult veterans discharged from 1 of 22 Veterans Integrated Service Networks with a psychiatric diagnosis between 1993 and 1998.

Bayes Theorem↗

PubMed2004

Underestimation of standard errors in multi-site time series studies.

Multi-site time series studies of the association of air pollution with mortality and morbidity have figured prominently in the literature as comprehensive approaches for estimating short-term effects of air pollution on health. Hierarchical models are generally used to combine site-specific information and to estimate pooled air pollution effects while taking into account both within-site statistical uncertainty and across-site heterogeneity. Within a site, characteristics of time series data of air pollution and health (small pollution effects, missing data, and highly correlated predictors) make the modeling of all sources of uncertainty challenging. One potential consequence is underestimation of the statistical variance of the site-specific effects to be combined.In this paper, we investigate the impact of variance underestimation on the pooled relative rate estimate. We focused on two-stage normal-normal hierarchical models and on underestimation of the statistical variance at the first stage. By mathematical considerations and simulation studies, we found that variance underestimation did not affect the pooled estimate substantially. However, the pooled estimate was somewhat sensitive to variance underestimation when the number of sites was small and underestimation was severe. These simulation results are applicable to any two-stage normal-normal hierarchical model for combining information of site-specific results (including meta-analyses), and they can easily be extended to more general hierarchical formulations. We also examined the impact of variance underestimation on the national average relative rate estimate from the National Morbidity, Mortality and Air Pollution Study. We found that variance underestimation as large as 40% had little effect on the national average.

Air Pollutants↗

PubMed2004

The National Morbidity, Mortality, and Air Pollution Study. Part III: PM10 concentration-response curves and thresholds for the 20 largest US cities.

Numerous studies have shown a positive association between daily mortality and particulate air pollution, even at concentrations below regulatory limits. These findings have motivated interest in the shape of the concentration-response relation. We developed flexible modeling strategies for time-series data that include spline and threshold concentration-response models. We applied these models to daily time-series data for the 20 largest US cities for 1987 through 1994, using concentration of particulate matter less than 10 microm in aerodynamic diameter (PM10*) as the exposure measure. The spline model showed a linear relation without indicating a threshold for the relative risks of death for all causes (total deaths) and for cardiovascular-respiratory causes in relation to PM10 concentration. By contrast, for causes other than cardiovascular-respiratory, the relative risk did not increase until the concentration reached approximately 50 microg/m3 PM10. For total mortality, a linear model without threshold was preferred to the threshold model and to the spline model, using the value of the Akaike information criterion (AIC). The findings were similar for combined cardiovascular and respiratory deaths. These findings indicate that linear models without a threshold are appropriate for assessing the effect of particulate air pollution on daily mortality even at current ambient levels.

Air Pollution↗

PubMed2003

p-Coumaroylnoradrenaline, a novel plant metabolite implicated in tomato defense against pathogens.

The Avr9 peptide elicitor from the fungus Cladosporium fulvum, the bacterial pathogen Pseudomonas syringae pathovar tomato carrying the avirulence gene avrPto (Pst (avrPto)), and the organophosphorous insecticide fenitrothion induce resistance-related responses in tomato lines carrying the Cf-9, Pto, and Fen genes, respectively. These responses were associated with synthesis of p-coumaroyloctopamine and p-coumaroylnoradrenaline, a novel compound for plants. In susceptible near isogenic tomato lines (Cf-0, pto, fen) and wounded tomato leaves, the levels of these compounds were reduced or undetectable. The elevated levels of p-coumaroyloctopamine and p-coumaroylnoradrenaline were accompanied by elevated mRNA levels of genes encoding phenylalanine ammonia lyase, p-coumarate CoA ligase, and hydroxycinnamoyl-CoA:tyramine N-(hydroxycinnamoyl)transferase (THT), enzymes that are involved in the hydroxycinnamic acid amide biosynthesis. Southern hybridization indicated that THT is encoded by a multigene family in tomato. Four different THT full-length cDNAs were derived by reverse transcriptase-PCR using degenerate primers based on potato and tobacco THT sequences. Transcripts for all four homologs were present in unchallenged tomato leaves, but only tomTHT1-3 was highly expressed following challenge with Pst (avrPto). Furthermore, tomTHT1-3 showed a more substantial and rapid induction in the incompatible interaction than in the compatible interaction. The cDNAs tomTHT1-3, tomTHT7-1, and tomTHT7-8 encoded proteins with a high degree of amino acid sequence homology, although the recombinant proteins had different preferences for octopamine and noradrenaline. The fourth cDNA, tomTHT1-4, directed synthesis of a truncated enzymatically inactive protein due to the presence of a premature stop codon.

Acyltransferases↗

PubMed2003

Modelling the random effects covariance matrix in longitudinal data.

A common class of models for longitudinal data are random effects (mixed) models. In these models, the random effects covariance matrix is typically assumed constant across subject. However, in many situations this matrix may differ by measured covariates. In this paper, we propose an approach to model the random effects covariance matrix by using a special Cholesky decomposition of the matrix. In particular, we will allow the parameters that result from this decomposition to depend on subject-specific covariates and also explore ways to parsimoniously model these parameters. An advantage of this parameterization is that there is no concern about the positive definiteness of the resulting estimator of the covariance matrix. In addition, the parameters resulting from this decomposition have a sensible interpretation. We propose fully Bayesian modelling for which a simple Gibbs sampler can be implemented to sample from the posterior distribution of the parameters. We illustrate these models on data from depression studies and examine the impact of heterogeneity in the covariance matrix on estimation of both fixed and random effects.

Antidepressive Agents↗

PubMed2003

Incorporating prior beliefs about selection bias into the analysis of randomized trials with missing outcomes.

In randomized studies with missing outcomes, non-identifiable assumptions are required to hold for valid data analysis. As a result, statisticians have been advocating the use of sensitivity analysis to evaluate the effect of varying assumptions on study conclusions. While this approach may be useful in assessing the sensitivity of treatment comparisons to missing data assumptions, it may be dissatisfying to some researchers/decision makers because a single summary is not provided. In this paper, we present a fully Bayesian methodology that allows the investigator to draw a 'single' conclusion by formally incorporating prior beliefs about non-identifiable, yet interpretable, selection bias parameters. Our Bayesian model provides robustness to prior specification of the distributional form of the continuous outcomes.

Acquired Immunodeficiency Syndrome↗

PubMed2002

Biosynthesis of a substituted cellulose from a mutant strain of Xanthomonas campestris.

In Xanthomonas campestris the genes involved in polysaccharide (xanthan) biosynthesis are located in a gene cluster (gum) of 16 kb. A Tn5 insertion mutant with a reduced slimy phenotype has been characterized. This mutant failed to produce the pentasaccharide repeating-unit of xanthan. Only three sugars were transferred to the prenyl phosphate intermediate. Several lines of evidence suggested that the lipid-associated saccharide was the trisaccharide reducing end of the pentasaccharide from the wild-type strain. This trisaccharide was built up from UDP-Glc and GDP-Man, and a glucose residue was at the reducing end, linked to an allylic prenol through a diphosphate bridge. Results from one- or two-stage reactions showed that the trisaccharide-P-P-polyprenol was the precursor of the polymer. This new polymer, a polytrisaccharide, was detected also in vivo. The transposon responsible for the mutation was located within gumK gene. Therefore, this gene encodes for the glycosyltransferase IV, which catalyses the transfer of glucuronic acid to the lipid-linked beta-D-Manp-(1-->3)-beta-D-Glcp-(1-->4)-beta-D-Glcp trisaccharide. A recombinant plasmid with the whole gum cluster restored the wild type phenotype.

Bacterial Proteins↗

PubMed2002

Prior exposure to lipopolysaccharide potentiates expression of plant defenses in response to bacteria.

Lipopolysaccharide (LPS) is a ubiquitous component of Gram-negative bacteria which has a number of diverse biological effects on eukaryotic cells. In contrast to the large body of work in mammalian and insect cells, the effects of LPS on plant cells have received little attention. LPS can induce defense-related responses in plants, but in many cases these direct effects are weak. Here we have examined the effects of prior inoculation of LPS on the induction of plant defense-related responses by phytopathogenic xanthomonads in leaves of pepper (Capsicum annuum). The resistance of pepper to incompatible strains of Xanthomonas axonopodis pv. vesicatoria or to X. campestris pv. campestris is associated with increased synthesis of the hydroxycinnamoyl-tyramine conjugates, feruloyl-tyramine (FT) and coumaroyl-tyramine (CT). FT and CT are produced only in trace amounts in response to compatible strains of X. axonopodis pv. vesicatoria. Treatment of leaves with LPS from a number of bacteria did not induce the synthesis of FT and CT but altered the kinetics of induction upon subsequent bacterial inoculation. In incompatible interactions FT and CT synthesis was accelerated, whereas in compatible interactions synthesis was also considerably enhanced. The ability of the tissue to respond more rapidly was induced within 4 h of LPS treatment and the potentiated state was maintained for at least 38 h. Earlier treatment with LPS also potentiated the expression of other defense responses such as transcription of genes encoding acidic beta-1,3-glucanase. Our findings indicate a wider role for LPS in plant-bacterial interactions beyond its limited activity as a direct inducer of plant defenses.

Capsicum↗

PubMed2000

Novel genes involved in the regulation of pathogenicity factor production within the rpf gene cluster of Xanthomonas campestris.

The synthesis of extracellular enzymes and extracellular polysaccharide (EPS) in Xanthomonas campestris pathovar campestris (Xcc) is subject to co-ordinate regulation by a cluster of genes called rpf (for regulation of pathogenicity factors). These genes are located within a 21.9 kb region of the chromosome isolated as the cosmid clone pIJ3020. The genes in the left-hand section of this region of the chromosome have previously been characterized. This paper reports on the genes in the right-hand section and on the phenotypes of mutants with transposon insertions in these genes. Sequence analysis identified eight genes or ORFs with the gene order rpfD-orf1-orf2-orf3-orf4-recJ-rpf E-greA. RecJ and GreA have established functions in recombination and transcriptional elongation, respectively. rpfD encoded a protein with some amino acid sequence relatedness to a hypothetical protein from Caulobacter crescentus and an autolysin response regulator in Bacillus subtilis. The predicted protein products of orf1, 2 and 3 were related to each other and had substantial amino acid sequence relatedness to hypothetical proteins from C. crescentus. Transposon insertions in orf1, 2 and 3 had no effect on the synthesis of extracellular enzymes or EPS. The predicted proteins RpfE and Orf4 showed the highest amino acid sequence relatedness to hypothetical proteins from Bordetella pertussis and Klebsiella pneumoniae, respectively. Transposon insertions in rpfE led to reduced levels of some extracellular enzymes (endoglucanase and protease) and increased levels of others (polygalacturonate lyase). Transposon insertions in orf4 had no effect on polygalacturonate lyase but led to reduced levels of protease and endoglucanase. Levels of EPS were reduced in both rpfE and orf4 mutants. These alterations in the levels of extracellular enzymes, which were relatively modest (between two- and threefold), did not affect the pathogenicity of Xcc on turnip. It is proposed that the gene designation should be rpfI for orf4.

Amino Acid Sequence↗

PubMed1998

Evidence for a role for the gumB and gumC gene products in the formation of xanthan from its pentasaccharide repeating unit by Xanthomonas campestris.

The biosynthesis of the extracellular polysaccharide xanthan in Xanthomonas campestris pv. campestris is directed by a cluster of 12 genes, gumB-gumM. Several xanthan-deficient mutants of the wild-type strain 8004 have previously been described which carry Tn5 insertions in this region of the chromosome. Here it is shown that the transposon insertion in one of these mutants, strain 8397, is located 15 bp upstream of the translational start site of the gumB gene. EDTA-treated cells of strain 8397 were able to synthesize the lipid-linked pentasaccharide repeating unit of xanthan from the three nucleotide sugar donors (UDP-glucose, GDP-mannose and UDP-glucuronic acid) but were unable to polymerize the pentasaccharide into mature xanthan. A subclone of the gum gene cluster carrying gumB and gumC restored xanthan production to strain 8397 to levels approximately 28% of the wild-type. In contrast, subclones carrying gumB or gumC alone were not effective. These results are discussed with reference to previous speculations, based on computer analysis, that gumB and gumC are both involved in the translocation of xanthan across the bacterial membranes.

Bacterial Proteins↗