Biomedical subjects

Anthony Almudevar

Publications and source records attributed to Anthony Almudevar.

9 recordsLinked to original sources

PubMed2006

A graphical approach to relatedness inference.

The estimation of relatedness structure in natural populations using molecular marker data has become an important tool in population biology, resulting in a variety of estimation procedures for specific sampling scenarios. In this article a general approach is proposed, in which the detailed relationship structure, typically a pedigree graph or partition, is considered to be the object of inference. This makes available tools used in complex model selection theory which have demonstrated effectiveness. An important advantage of this approach is that it permits a fully Bayesian approach to the problem, providing a principled and accessible way to measure statistical error. The approach is demonstrated by applying the minimum description length principle. This technique is used in model selection to provide a rational way of comparing models of varying complexity. We show how the resulting score may be interpreted and applied as a Bayesian posterior density.

Bayes Theorem↗

PubMed2006

Deletion of prostaglandin E2 EP2 receptor protects against ultraviolet-induced carcinogenesis, but increases tumor aggressiveness.

Ultraviolet (UV) light is a complete carcinogen inducing and promoting squamous-cell carcinoma (SCC) of the skin. Recent work has shown that SCC initiation and promotion are enhanced by prostaglandin E2 (PGE2). PGE2 interacts with specific EP receptors to regulate cellular functions. Previous work from our group has shown that the prostaglandin E2 EP2 receptor is a powerful regulator of keratinocyte growth. SKH-1 hairless mice lacking the EP2 receptor were therefore studied to understand how this growth signaling pathway contributes to photocarcinogenesis. Our data indicate that UV-irradiated mice lacking EP2 receptors exhibit decreased proliferation and a poor capacity for epidermal hypertrophy in response to UV injury. In a chronic irradiation model, these animals were protected from tumor formation, developing 50% fewer tumors than wild-type controls. Despite this capacity to protect against tumorigenesis, animals lacking EP2 receptors grew tumors that were larger in size, with a more aggressive phenotype. Further study suggested that this susceptibility may be associated with synthesis of active metalloproteinase enzymes in greater quantities than keratinocytes expressing the EP2 receptor, thereby enhancing the invasive potential of EP2-/- cells.

Animals↗

PubMed2006

Using complexity for the estimation of Bayesian networks.

Statistical inference of graphical models has become an important tool in the reconstruction of biological networks of the type which model, for example, gene regulatory interactions. In particular, the construction of a score-based Bayesian posterior density over the space of models provides an intuitive and computationally feasible method of assessing model uncertainty and of assigning statistical confidence to structural features. One problem which frequently occurs with this approach is the tendency to overestimate the degree of model complexity. Spurious graphical features obtained in this way may affect the inference in unpredictable ways, even when using scoring techniques, such as the Bayesian Information Criterion (BIC), that are specifically designed to compensate for overfitting. In this article we propose a simple adjustment to a BIC-based scoring procedure. The method proceeds in two steps. In the first step we derive an independent estimate of the parametric complexity of the model. In the second we modify the BIC score so that the mean parametric complexity of the posterior density is equal to the estimated value. The method is applied to a set of test networks, and to a collection of genes from the yeast genome known to possess regulatory relationships. A Bayesian network model with binary responses is employed. In the examples considered, we find that the number of spurious graph edges inferred is reduced, while the effect on the identification of true edges is minimal.

Algorithms↗

PubMed2006

Dalhousie dyspnea scales: Pictorial scales to measure dyspnea during induced bronchoconstriction.

The aim of this study was to validate our Dalhousie Dyspnea Scales in children referred for histamine bronchoprovocation challenge. Seventy-four children rated their dyspnea after each FEV(1) measurement following inhalation of doubling histamine concentrations from 0.125 to 8.0 mg/ml by the standard tidal breathing method. Serial FEV(1) and dyspnea rating using the Dalhousie Dyspnea Scales were recorded and Kendall's tau was computed for dyspnea rating versus fall in FEV(1). Subjects were split into those with positive (DeltaFEV(1) >or= 20% with PC(20) <or= 8 mg/ml) or negative histamine challenge test. During histamine inhalation, dyspnea ratings on each of the subscales rose as FEV(1) fell across subjects, whether or not they were histamine-responsive (main effect), and then fell dramatically following relief of induced obstruction by bronchodilator.The Dalhousie Dyspnea Scales are useful and accurate tools to measure dyspnea due to bronchoconstriction in children.

Administration, Inhalation↗

PubMed2006

Utility of correlation measures in analysis of gene expression.

The role of the correlation structure of gene expression data are two-fold: It is a source of complications and useful information at the same time. Ignoring the strong stochastic dependence between gene expression levels in statistical methodologies for microarray data analysis may deteriorate their performance. However, there is a host of valuable information in the correlation structure that deserves a closer look. A proper use of correlation measures can remedy deficiencies of currently practiced methods that are focused too heavily on strong effects in terms of differential expression of genes. The present paper discusses the utility of correlation measures in microarray data analysis and gene regulatory network reconstruction, along with various pitfalls in both research areas that have been uncovered in methodological studies. These issues have broad applicability to all genomic studies examining the biology, diagnosis, and treatment of neurological disorders.

Animals↗

PubMed2005

Relationship between FEV1 and peak oxygen uptake in children with cystic fibrosis.

Cross-sectional data do not truly convey the manner in which declining lung function affects peak oxygen uptake (peak VO2) within a given patient with cystic fibrosis. We hypothesized that there would be a concomitant decline in peak VO2 with FEV1 over time. Twenty-eight children aged 8-17 years with cystic fibrosis performed annual ergometer tests over a 5-year period to determine peak VO2 and within-patient predictors of change in peak VO2. Analysis was done using a mixed-effects model. During the study period, the annual decline in FEV1 averaged 2.7% of the predicted value per year. Peak VO2 fell during the observation period in 70% of patients, with an average annualized decline of 1.9 ml x min(-1) x kg(-1). This rate of decline was greater in older children in contrast to younger children, some of whom had an improvement in peak VO2 over the first few years, consistent with growth and maturation. There was no difference in this rate of decline between sexes, but girls started with a slightly lower peak VO2 (37.9 vs. 45.1 ml x min(-1) x kg(-1)). In patients with FEV1 <80% predicted, declining FEV1 was highly correlated with falling peak VO2, whereas it remained stable over 4-5 years in patients whose FEV1 was >80% predicted and remained in that range. We conclude that peak VO2 remains stable or rises slightly over time in younger patients, while it shows a downward trend in older children with CF, particularly once FEV1 falls below 80% predicted. Peak VO2 is correlated with FEV1 during childhood in patients with cystic fibrosis, and both FEV1 and age influence peak VO2.

Adolescent↗

PubMed2003

A simulated annealing algorithm for maximum likelihood pedigree reconstruction.

The calculation of maximum likelihood pedigrees for related organisms using genotypic data is considered. The problem is formulated so that the domain of optimization is a permutation space. This is a feature shared by the travelling salesman problem, for which simulated annealing is known to be effective. Using this technique it is found that pedigrees can be reconstructed with minimal error using genotypic data of a quality currently realizable. In complex pedigrees accurate reconstruction can be done with no a priori age or sex information. For smaller numbers of individuals a method of efficiently enumerating all admissible pedigrees of nonzero likelihood is given.

Algorithms↗

PubMed2003

Coxiella burnetii seropositivity in parturient women is associated with adverse pregnancy outcomes.

OBJECTIVE: We conducted a cohort study of parturient women in an area with endemic Q fever infection to determine whether those seropositive for Coxiella burnetii had evidence of adverse birth outcomes. STUDY DESIGN: From June 1997 to November 1998, the cord blood of all women delivered at our health center was tested for antibodies to C burnetii by indirect immunofluorescence antibody test by using purified whole cell strain Nine Mile antigens. A titer of 1:8 or greater to either phase I or phase II antigens was considered seropositive. Placentas of a sample of cases and seronegative controls had polymerase chain reaction and culture performed. RESULTS: Evidence of prior infection with C burnetii was found in 3.8% (291/7658) of all parturient women. In a multivariate logistic regression, an association was seen between seropositivity (phase I titer >or= 1:8 or phase II titer >or= 1:32) and newborn gestational age >or=36 weeks (phase I antibody, odds ratio [OR] 2.4, 95% CI 1.3-4.3, P =.005; phase II antibody, OR 1.9, 95% CI 1.02-3.7, P =.04). Women with phase I antibody were more likely to have a prior or current neonatal death (phase I OR 3.2, 95% CI 1.09-9.3, P =.03). No placental samples from 153 seropositive or 93 seronegative women had Q fever by polymerase chain reaction or culture. CONCLUSION: About 4% of parturient women in this endemic area have evidence of previous exposure to C burnetii and this exposure is associated with adverse pregnancy outcomes. The pathogenesis of this association remains to be determined.

Adolescent↗

PubMed2002

Screening for adolescent depression: comparison of the Kutcher Adolescent Depression Scale with the Beck depression inventory.

Self-report instruments commonly used to assess depression in adolescents have limited or unknown reliability and validity in this age group. We describe a new self-report scale, the Kutcher Adolescent Depression Scale (KADS), designed specifically to diagnose and assess the severity of adolescent depression. This report compares the diagnostic validity of the full 16-item instrument, brief versions of it, and the Beck Depression Inventory (BDI) against the criteria for major depressive episode (MDE) from the Mini International Neuropsychiatric Interview (MINI). Some 309 of 1,712 grade 7 to grade 12 students who completed the BDI had scores that exceeded 15. All were invited for further assessment, of whom 161 agreed to assessment by the KADS, the BDI again, and a MINI diagnostic interview for MDE. Receiver operating characteristic (ROC) curve analysis was used to determine which KADS items best identified subjects experiencing an MDE. Further ROC curve analyses established that the overall diagnostic ability of a six-item subscale of the KADS was at least as good as that of the BDI and was better than that of the full-length KADS. Used with a cutoff score of 6, the six-item KADS achieved sensitivity and specificity rates of 92% and 71%, respectively-a combination not achieved by other self-report instruments. The six-item KADS may prove to be an efficient and effective means of ruling out MDE in adolescents.

Adolescent↗