TESTING STATISTICAL HYPOTHESIS ON RANDOM TREES AND APPLICATIONS TO THE PROTEIN CLASSIFICATION PROBLEM

Efficient automatic protein classification is of central importance in genomic annotation. As an independent way to check the reliability of the classification, we propose a statistical approach to test if two sets of protein domain sequences coming from two families of the Pfam database are significantly different. We model protein sequences as realizations of Variable Length Markov Chains (VLMC) and we use the context trees as a signature of each protein family. Our approach is based on a Kolmogorov-Smirnov-type goodness-of-fit test proposed by Balding et at. [Limit theorems for sequences of random trees (2008), DOI: 10.1007/s11749-008-0092-z]. The test statistic is a supremum over the space of trees of a function of the two samples; its computation grows, in principle, exponentially fast with the maximal number of nodes of the potential trees. We show how to transform this problem into a max-flow over a related graph which can be solved using a Ford-Fulkerson algorithm in polynomial time on that number. We apply the test to 10 randomly chosen protein domain families from the seed of Pfam-A database (high quality, manually curated families). The test shows that the distributions of context trees coming from different families are significantly different. We emphasize that this is a novel mathematical approach to validate the automatic clustering of sequences in any context. We also study the performance of the test via simulations on Galton-Watson related processes.

Hypothesis testing in an errors-in-variables model with heteroscedastic measurement errors

In many epidemiological studies it is common to resort to regression models relating incidence of a disease and its risk factors. The main goal of this paper is to consider inference on such models with error-prone observations and variances of the measurement errors changing across observations. We suppose that the observations follow a bivariate normal distribution and the measurement errors are normally distributed. Aggregate data allow the estimation of the error variances. Maximum likelihood estimates are computed numerically via the EM algorithm. Consistent estimation of the asymptotic variance of the maximum likelihood estimators is also discussed. Test statistics are proposed for testing hypotheses of interest. Further, we implement a simple graphical device that enables an assessment of the model`s goodness of fit. Results of simulations concerning the properties of the test statistics are reported. The approach is illustrated with data from the WHO MONICA Project on cardiovascular disease. Copyright (C) 2008 John Wiley & Sons, Ltd.

In vitro wear resistance of three types of polymethyl methacrylate denture teeth

The wear resistance of denture teeth is important to the longevity of removable prostheses of edentulous patients. The ability of denture teeth to maintain a stable occlusal relationship over time may be influenced by this property. The purpose of this in vitro study was to evaluate the wear resistance of polymethyl methacrylate (PMMA) denture teeth based on their chemical composition when opposed by a ceramic antagonist. The maxillary canines (n=10) of 3 PMMA denture teeth (Trubyte Biotone, cross-linked PMMA; Trilux, highly cross-linked IPN (interpenetrating polymer network)-PMMA; and Vivodent, highly cross-linked PMMA) were secured in an in vitro 2-body wear-testing apparatus that produced sliding contact of the specimens (4.5 cycles/s, sliding distance of 20 mm, under 37°C running water) against glazed or airborne particle abraded ceramic. Wear resistance was measured as height loss (mm) under 300 g (sliding force) after 100,000 cycles, using a digital measuring microscope. Mean values were analyzed by 2-way ANOVA and Tukey's test (a=0.05). The wear of Trubyte Biotone (0.93 ± 0.14 mm) was significantly higher than that of both other types of teeth tested against abraded ceramic (p<0.05). The Vivodent tooth (0.64 ± 0.17 mm) exhibited the best wear resistance among the denture teeth tested against airborne particle abraded ceramic. There were no statistically significant differences (p>0.05) in wear among the 3 denture teeth evaluated against glazed ceramic. Trilux and Vivodent teeth tested against either glazed or airborne particle abraded ceramic did not differ significantly from each other (p<0.05). All teeth showed significantly more wear against airborne particle abraded ceramic than against glazed ceramic (p<0.05). In conclusion, the three types of PMMA denture teeth presented significantly different wear resistance against the abraded ceramic. The high-strength PMMA denture teeth were more wear-resistant than the conventional PMMA denture tooth.

Array-CGH testing in spontaneous abortions with normal karyotypes

In about 50% of first trimester spontaneous abortion the cause remains undetermined after standard cytogenetic investigation. We evaluated the usefulness of array-CGH in diagnosing chromosome abnormalities in products of conception from first trimester spontaneous abortions. Cell culture was carried out in short- and long-term cultures of 54 specimens and cytogenetic analysis was successful in 49 of them. Cytogenetic abnormalities (numerical and structural) were detected in 22 (44.89%) specimens. Subsequent, array-CGH based on large insert clones spaced at ~1 Mb intervals over the whole genome was used in 17 cases with normal G-banding karyotype. This revealed chromosome aneuplodies in three additional cases, giving a final total of 51% cases in which an abnormal karyotype was detected. In keeping with other recently published works, this study shows that array-CGH detects abnormalities in a further ~10% of spontaneous abortion specimens considered to be normal using standard cytogenetic methods. As such, array-CGH technique may present a suitable complementary test to cytogenetic analysis in cases with a normal karyotype.

Treadmill exercise testing of asymptomatic men and women without evidence of heart disease

The aim of this study was to test the hypothesis of differences in performance including differences in ST-T wave changes between healthy men and women submitted to an exercise stress test. Two hundred (45.4%) men and 241 (54.6%) women (mean age: 38.7 ± 11.0 years) were submitted to an exercise stress test. Physiologic and electrocardiographic variables were compared by the Student t-test and the chi-square test. To test the hypothesis of differences in ST-segment changes, data were ranked with functional models based on weighted least squares. To evaluate the influence of gender and age on the diagnosis of ST-segment abnormality, a logistic model was adjusted; P < 0.05 was considered to be significant. Rate-pressure product, duration of exercise and estimated functional capacity were higher in men (P < 0.05). Sixteen (6.7%) women and 9 (4.5%) men demonstrated ST-segment upslope ≥0.15 mV or downslope ≥0.10 mV; the difference was not statistically significant. Age increase of one year added 4% to the chance of upsloping of segment ST ≥0.15 mV or downsloping of segment ST ≥0.1 mV (P = 0.03; risk ratio = 1.040, 95% confidence interval (CI) = 1.002-1.080). Heart rate recovery was higher in women (P < 0.05). The chance of women showing an increase of systolic blood pressure ≤30 mmHg was 85% higher (P = 0.01; risk ratio = 1.85, 95%CI = 1.1-3.05). No significant difference in the frequency of ST-T wave changes was observed between men and women. Other differences may be related to different physical conditioning.

Estimating HIV-1 incidence using the serologic testing algorithm for recent HIV infections at HIV counseling and testing centers in the city of São Paulo, Brazil

The network of HIV counseling and testing centers in São Paulo, Brazil is a major source of data used to build epidemiological profiles of the client population. We examined HIV-1 incidence from November 2000 to April 2001, comparing epidemiological and socio-behavioral data of recently-infected individuals with those with long-standing infection. A less sensitive ELISA was employed to identify recent infection. The overall incidence of HIV-1 infection was 0.53/100/year (95% CI: 0.31-0.85/100/year): 0.77/100/year for males (95% CI: 0.42-1.27/100/year) and 0.22/100/ year (95% CI: 0.05-0.59/100/year) for females. Overall HIV-1 prevalence was 3.2% (95% CI: 2.8-3.7%), being 4.0% among males (95% CI: 3.3-4.7%) and 2.1% among females (95% CI: 1.6-2.8%). Recent infections accounted for 15% of the total (95% CI: 10.2-20.8%). Recent infection correlated with being younger and male (p = 0.019). Therefore, recent infection was more common among younger males and older females.

IgM e IgG como marcadores da infecção transplacentária por Neospora caninum em fetos bovinos

O objetivo deste estudo foi determinar a ocorrência de anticorpos anti-Neospora caninum em 260 amostras de soro coletadas de fetos bovinos de julho de 2007 a março de 2008, em abatedouro do município de Santa Maria, Rio Grande do Sul, Brasil. Para detecção de anticorpos anti-N. caninum, a técnica de imunofluorescência indireta foi utilizada tanto para a detecção de imunoglobulinas G e M. Amostras com títulos e" 25 foram consideradas positivas. Das 260 amostras testadas, 15% (39/260) foram positivas para anticorpos anti-N. caninum. Destas, em 38 (97,4%) foi detectada a presença de IgG anti-N. caninum e em seis (15,4%) de IgM. Em cinco amostras (12,8%) detectaram-se ambos, IgG e IgM. Os resultados reafirmam a habilidade do N. caninum em determinar infecção fetal. A pesquisa de IgM foi de limitada importância na detecção da infecção via transplacentária em soro fetal bovino.

The ability of the BANA test to detect different levels of P. gingivalis, T. denticola and T. forsythia

The aim of this study was to evaluate the ability of the BANA Test to detect different levels of Porphyromonas gingivalis, Treponema denticola and Tannerella forsythia or their combinations in subgingival samples at the initial diagnosis and after periodontal therapy. Periodontal sites with probing depths between 5-7 mm and clinical attachment level between 5-10 mm, from 53 subjects with chronic periodontitis, were sampled in four periods: initial diagnosis (T0), immediately (T1), 45 (T2) and 60 days (T3) after scaling and root planing. BANA Test and Checkerboard DNA-DNA hybridization identified red complex species in the subgingival biofilm. In all experimental periods, the highest frequencies of score 2 (Checkerboard DNA-DNA hybridization) for P. gingivalis, T. denticola and T. forsythia were observed when strong enzymatic activity (BANA) was present (p < 0.01). The best agreement was observed at initial diagnosis. The BANA Test sensitivity was 95.54% (T0), 65.18% (T1), 65.22% (T2) and 50.26% (T3). The specificity values were 12.24% (T0), 57.38% (T1), 46.27% (T2) and 53.48% (T3). The BANA Test is more effective for the detection of red complex pathogens when the bacterial levels are high, i.e. in the initial diagnosis of chronic periodontitis.

Working at night and work ability among nursing personnel: when precarious employment makes the diVerence

Purpose To test the association between night work and work ability, and verify whether the type of contractual employment has any inXuence over this association. Methods Permanent workers (N = 642) and workers with precarious jobs (temporary contract or outsourced; N = 552) were interviewed and Wlled out questionnaires concerning work hours and work ability index. They were classiWed into: never worked at night, ex-night workers, currently working up to Wve nights, and currently working at least six nights/2-week span. Results After adjusting for socio-demography and work variables, current night work was signiWcantly associated with inadequate WAI (vs. day work with no experience in night work) only for precarious workers (OR 2.00, CI 1.01- 3.95 and OR 1.85, CI 1.09-3.13 for those working up to Wve nights and those working at least six nights in 2 weeks, respectively). Conclusions Unequal opportunities at work and little experience in night work among precarious workers may explain their higher susceptibility to night work

Parametric model for the analysis of concrete expansion due to alkali-aggregate reaction

The alkali-aggregate reaction (AAR) is a chemical reaction that provokes a heterogeneous expansion of concrete and reduces important properties such as Young's modulus, leading to a reduction in the structure's useful life. In this study, a parametric model is employed to determine the spatial distribution of the concrete expansion, combining normalized factors that influence the reaction through an AAR expansion law. Optimization techniques were employed to adjust the numerical results and observations in a real structure. A three-dimensional version of the model has been implemented in a finite element commercial package (ANSYS(C)) and verified in the analysis of an accelerated mortar test. Comparisons were made between two AAR mathematical descriptions for the mechanical phenomenon, using the same methodology, and an expansion curve obtained from experiment. Some parametric studies are also presented. The numerical results compared very well with the experimental data validating the proposed method.

A reliable measure of similarity based on dependency for short time series: an application to gene expression networks

Background: Microarray techniques have become an important tool to the investigation of genetic relationships and the assignment of different phenotypes. Since microarrays are still very expensive, most of the experiments are performed with small samples. This paper introduces a method to quantify dependency between data series composed of few sample points. The method is used to construct gene co-expression subnetworks of highly significant edges. Results: The results shown here are for an adapted subset of a Saccharomyces cerevisiae gene expression data set with low temporal resolution and poor statistics. The method reveals common transcription factors with a high confidence level and allows the construction of subnetworks with high biological relevance that reveals characteristic features of the processes driving the organism adaptations to specific environmental conditions. Conclusion: Our method allows a reliable and sophisticated analysis of microarray data even under severe constraints. The utilization of systems biology improves the biologists ability to elucidate the mechanisms underlying celular processes and to formulate new hypotheses.

Development and mechanical testing of a short intramedullary nail for fixation of femoral rotational osteotomy in cerebral palsy patients

Background: Rotational osteotomy is frequently indicated to correct excessive femoral anteversion in cerebral palsy patients. Angled blade plate is the standard fixation device used when performed in the proximal femur, but extensile exposure is required for plate accommodation. The authors developed a short locked intramedullary nail to be applied percutaneously in the fixation of femoral rotational osteotomies in children with cerebral palsy and evaluated its mechanical properties. Methods: The study was divided into three stages. In the first part, a prototype was designed and made based on radiographic measurements of the femoral medullary canal of ten-year-old patients. In the second, synthetic femoral models based on rapid-prototyping of 3D reconstructed images of patients with cerebral palsy were obtained and were employed to adjust the nail prototype to the morphological changes observed in this disease. In the third, rotational osteotomies were simulated using synthetic femoral models stabilized by the nail and by the AO-ASIF fixed-angle blade plate. Mechanical testing was done comparing both devices in bending-compression and torsion. Results: The authors observed proper adaptation of the nail to normal and morphologically altered femoral models, and during the simulated osteotomies. Stiffness in bending-compression was significantly higher in the group fixed by the plate (388.97 +/- 57.25 N/mm) than in that fixed by the nail (268.26 +/- 38.51 N/mm) as torsional relative stiffness was significantly higher in the group fixed by the plate (1.07 +/- 0.36 Nm/degrees) than by the nail (0.35 +/- 0.13 Nm/degrees). Conclusions: Although the device presented adequate design and dimension to fit into the pediatric femur, mechanical tests indicated that the nail was less stable than the blade plate in bending-compression and torsion. This may be a beneficial property, and it can be attributed to the more flexible fixation found in intramedullary devices.

Integration and visualization of systems biology data in context of the genome

Background: High-density tiling arrays and new sequencing technologies are generating rapidly increasing volumes of transcriptome and protein-DNA interaction data. Visualization and exploration of this data is critical to understanding the regulatory logic encoded in the genome by which the cell dynamically affects its physiology and interacts with its environment. Results: The Gaggle Genome Browser is a cross-platform desktop program for interactively visualizing high-throughput data in the context of the genome. Important features include dynamic panning and zooming, keyword search and open interoperability through the Gaggle framework. Users may bookmark locations on the genome with descriptive annotations and share these bookmarks with other users. The program handles large sets of user-generated data using an in-process database and leverages the facilities of SQL and the R environment for importing and manipulating data. A key aspect of the Gaggle Genome Browser is interoperability. By connecting to the Gaggle framework, the genome browser joins a suite of interconnected bioinformatics tools for analysis and visualization with connectivity to major public repositories of sequences, interactions and pathways. To this flexible environment for exploring and combining data, the Gaggle Genome Browser adds the ability to visualize diverse types of data in relation to its coordinates on the genome. Conclusions: Genomic coordinates function as a common key by which disparate biological data types can be related to one another. In the Gaggle Genome Browser, heterogeneous data are joined by their location on the genome to create information-rich visualizations yielding insight into genome organization, transcription and its regulation and, ultimately, a better understanding of the mechanisms that enable the cell to dynamically respond to its environment.

Adding fever to WHO criteria for diagnosing pneumonia enhances the ability to identify pneumonia cases among wheezing children

Objective To examine the ability of the criteria proposed by the WHO to identify pneumonia among cases presenting with wheezing and the extent to which adding fever to the criteria alters their performance. Design Prospective classification of 390 children aged 2-59 months with lower respiratory tract disease into five diagnostic categories, including pneumonia. WHO criteria for the identification of pneumonia and a set of such criteria modified by adding fever were compared with radio-graphically diagnosed pneumonia as the gold standard. Results The sensitivity of the WHO criteria was 94% for children aged <24 months and 62% for those aged >= 24 months. The corresponding specificities were 20% and 16%. Adding fever to the WHO criteria improved specificity substantially (to 44% and 50%, respectively). The specificity of the WHO criteria was poor for children with wheezing (12%). Adding fever improved this substantially (to 42%). The addition of fever to the criteria apparently reduced their sensitivity only marginally (to 92% and 57%, respectively, in the two age groups). Conclusion The authors' results reaffirm that the current WHO criteria can detect pneumonia with high sensitivity, particularly among younger children. They present evidence that the ability of these criteria to distinguish between children with pneumonia and those with wheezing diseases might be greatly enhanced by the addition of fever.