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PubMed1994

Group differences in measures of voice production and revised values of maximum airflow declination rate.

In previous reports, aerodynamic and acoustic measures of voice production were presented for groups of normal male and female speakers [Holmberg et al., J. Acoust. Soc. Am. 84, 511-529 (1988); J. Voice 3, 294-305 (1989)] that were used as norms in studies of voice disorders [Hillman et al., J. Speech Hear. Res. 32, 373-392 (1989); J. Voice 4, 52-63 (1990)]. Several of the measures were extracted from glottal airflow waveforms that were derived by inverse filtering a high-time-resolution oral airflow signal. Recently, the methods have been updated and a new study of additional subjects has been conducted. This report presents previous (1988) and current (1993) group mean values of sound pressure level, fundamental frequency, maximum airflow declination rate, ac flow, peak flow, minimum flow, ac-dc ratio, inferred subglottal air pressure, average flow, and glottal resistance. Statistical tests indicate overall group differences and differences for values of several individual parameters between the 1988 and 1993 studies. Some inter-study differences in parameter values may be due to sampling effects and minor methodological differences; however, a comparative test of 1988 and 1993 inverse filtering algorithms shows that some lower 1988 values of maximum flow declination rate were due at least in part to excessive low-pass filtering in the 1988 algorithm. The observed differences should have had a negligible influence on the conclusions of our studies of voice disorders.

Air Pressure↗
PubMedDate not supplied

The role of warmup in muscular injury prevention.

This study is an attempt to provide biomechanical support for the athletic practice of warming up prior to an exercise task to reduce the incidence of injury. Tears in isometrically preconditioned (stimulated before stretching) muscle were compared to tears in control (nonstimulated) muscle by examining four parameters: 1) force and 2) change of length required to tear the muscle, 3) site of failure, and 4) length-tension deformation. The tibialis anterior (TA), the extensor digitorum longus (EDL), and flexor digitorum longus (EDL) muscles from both hindlimbs of rabbits comprised our experimental model. Isometrically preconditioned TA (P less than 0.001), EDL (P less than 0.005), and FDL (P less than 0.01) muscles required more force to fail than their contralateral controls. Preconditioned TA (P less than 0.05), EDL (P less than 0.001), and FDL (P less than 0.01) muscles also stretched to a greater length from rest before failing than their nonpreconditioned controls. The site of failure in all of the muscles was the musculotendinous junction; thus, the site of failure was not altered by condition. The length-tension deformation curves for all three muscle types showed that in every case the preconditioned muscles attained a lesser force at each given increase in length before failure, showing a relative increase in elasticity, although only the EDL showed a statistically significant difference. From our data, it may be inferred that physiologic warming (isometric preconditioning) is of benefit in preventing muscular injury by increasing the and length to failure and elasticity of the muscle-tendon unit.

Animals↗
PubMed2006

Online updating of space-time disease surveillance models via particle filters.

Online surveillance of disease has become an important issue in public health. In particular, the space-time monitoring of disease plays an important part in any syndromic system. However, methodology for these systems is generally lacking. One approach to space-time monitoring of health data is to consider the space-time model parameters as the focus and to monitor their changes as multivariate time series (Lawson AB. Some considerations in spatial-temporal analysis of public health surveillance data. In Brookmeyer R, Stroup DF eds. Monitoring the Health of Populations. Oxford University Press, 2004; Vidal Rodeiro CL, Lawson AB. Monitoring changes in spatio-temporal maps of disease. Biometrical Journal 2006; to appear). However with complex space-time models, this becomes very time consuming. Some simplifications may be necessary and these can be made in a number of ways. In this article, the focus is on particle filters that can be used to resample the history of the process and thereby reduce computation time. This article describes a particular case of particle filters, the resample-move algorithm, proposed by Gilks and Berzuini (Gilks WR, Berzuini C. Following a moving target--Monte Carlo inference for dynamic Bayesian models. Journal of the Royal Statistical Society, Series B 2001; 63: 127-46), in the context of disease map surveillance. This is followed by an application to a real data set in which a comparison between the use of Markov chain Monte Carlo methods and the resample-move algorithm is carried out.

Algorithms↗
PubMed2004

A mixed model approach to identify yeast transcriptional regulatory motifs via microarray experiments.

A genome-wide location analysis method has been introduced as a means to simultaneously study protein-DNA binding interactions for a large number of genes on a microarray platform. Identification of interactions between transcription factors (TF) and genes provide insight into the mechanisms that regulate a variety of cellular responses. Drawing proper inferences from the experimental data is key to finding statistically significant TF-gene binding interactions. We describe how the analysis and interpretation of genome-wide location data can be fit into a traditional statistical modeling framework that considers the data across all arrays and formulizes appropriate hypothesis tests. The approach is illustrated with data from a yeast transcription factor binding experiment that illustrates how identified TF-gene interactions can enhance initial exploration of transcriptional regulatory networks. Examples of five kinds of transcriptional regulatory structure are also demonstrated. Some stark differences with previously published results are explored.

Journal Article↗
PubMed1976

[Nutrition and cancer (author's transl)].

The problem of a relationship between nutrition and cancer has to be approached from two different points of view: 1. Direct effect of carcinogens present in foods or in food additives (direct carcinogenesis), 2. In-vivo synthesis of carcinogens caused by changes in metabolism due to altered dietary habits (indirect carcinogenesis). For the second mechanism, we have to make a distinction between the effects of nutritional deficiency and of nutritional excess. Some examples from animal experiments are presented. In man, possible relationships between nutrition and cancer are postulated mainly for tumors of the gastrointestinal tract and recently also for hormone-dependent cancers. Epidemiological evidence points to the major importance of the indirect way of carcinogenesis caused by specific nutritional deficiencies and excesses. Experimental studies in man are difficult to perform. Therefore, most hypotheses are based on statistical associations, and great caution is required in drawing inferences on causal relationships. Cancers of the upper and lower gastrointestinal tract epidemiologically behave in a different way, the former showing a marked decrease in most western countries, the latter a slight increase. The etiology of the cancers of the esophagus and stomach has still to be determined in spite of many hypotheses. Migrant studies show a major effect of environmental rather than genetic factors. Substantial differences in dietary habits between countries with high and low incidence of stomach cancer (Japan and United States) point to the importance of nutrition as an etiological factor with a high probability, but no specific dietary components have been identified so far. The same is true for cancer of the large bowel. Recent hypotheses suggest that dietary factors may relate to cancer of the colon by their effect on bile production and on the bacterial makeup of faeces which in turn might be transforming bile acids into active carcinogens. There is, however, disagreement about the specific dietary component responsible for this model of carcinogenesis. BURKITT stresses the importance of the lower consumption of dietary fiber, resulting in retarded bowel function and additional time for bacterial proliferation and degradation by bacteria of bile acids. WYNDER, on the other hand, explains the increased bile acid and neutral sterol excretion and microbial modification of these compounds with the high content of animal fat in the western diet. With hormone-dependent cancers (breast, endometrium, ovary, prostate), a correlation has been shown between body weight and height and breast cancer as well as between overweight and cancer of the endometrium. Which aspect of diet, if any, is responsible for changes in hormone metabolism, resulting in an increased risk of these cancers, is still to be proved. On the basis of current knowledge, it is extremely difficult to draw inferences for preventive action. Certainly, a cancer-preventing diet cannot be established...

Adult↗
PubMed2001

Data mining for on-line support of general practice.

Statistical relationships among symptoms, diagnoses and treatments can be inferred from large data-bases of health records. We investigate how these "empirical norms" can be utilized to improve the efficiency and quality assurance capability of on-line systems in General Practice medicine. Using a survey-based database of General Practice records, we assess hotlists (case sensitive menus) of diagnoses to speed data entry. We also explore norm violation as an indicator of poor quality in practice or data recording. We find that efficient hotlists of diagnoses can be generated from symptoms. Also, we find that less frequently used hypertension treatments are assessed as of a lower quality than more common ones. The results support the hypothesis that empirical norms have a role to play in improved General Practice systems.

Australia↗
PubMed2002

Insomnia and hypnotic use in Campo Grande general population, Brazil.

The insomnia prevalence in general population was determined by means of 408 home interviews of adults, in a representative sample of Campo Grande city, Brazil. The random sample was stratified by sex, age and economic social status. Insomnia subtypes evaluated were the disorders of sleep initiation (DSI), sleep maintenance (DSM) and early awakening (DEA). A structured questionnaire was used with the consent from the interviewed subjects. Statistics used chi-square, and Fisher tests; and inferences based on binomial distribution parameters; the significance level was 5% and confidence interval (CI) was 95%. The general prevalence of insomnia was 19.1% (sd=2.0%), mostly women (p=0.0015), and people of less years of schooling (p=0.0317), subtype DSI (14.2%, p=0.0043), and chronic (p=0.7022). Hypnotic drugs were used by 6.9%(sd=1.3%) in the last month. Use in the last 2 years, 70.3% mostly insomniacs (p<0.0001), women (p=0.0372) and people over 30 years of age (p=0.0536).

Adult↗
PubMedDate not supplied

[Methods of computer modeling and conformational mobility of DNA duplexes].

The review is focused on issues of transferability of the context-sensitive conformational characteristics of DNA estimated from crystallographic structural data on the DNA in aqueous solution. The state of the art in molecular dynamics of charged biopolymers in aqueous solution is covered. Elaboration of expedient force fields and algorithms of calculating long-range electrostatic interactions and solving combined equations of atomic motion have made it possible to generate stable nanosecond trajectories of thermal atomic motion of the biopolymer in aqueous solution in the presence of counterions and salt ions over reasonable time. Tools for analyzing the atomic statistical trajectories of DNA duplexes in aqueous solution to infer context-sensitive conformational dynamic characteristics are discussed together with advances in simulating the mechanisms of global axial bend in DNA duplexes. These techniques allow one to consecutively analyze relationships between the contextual composition of the duplex and the basic modes of essential motions, their amplitude and extent of fluctuation. Development of satisfactory methods for estimating the free energy of biopolymer conformations in solution permits qualitative assessment of the conformational thermodynamic stability of biopolymers and their complexes.

Computer Simulation↗
PubMed1995

NHS "indicators of success": what do they tell us? Radical Statistics Health Group.

In the absence of any systematic evaluation of the changes it has made to the NHS, the government cites three "indicators of success." These are record numbers of patients treated, shorter waiting times for hospital treatment, and more children being immunised against the main childhood diseases. Closer inspection of the statistics reveals that they do not support the conclusions inferred from them and that they are misleading measures of the impact of the changes made to the NHS.

Ambulatory Care↗
PubMed2003

SARS associated coronavirus has a recombinant polymerase and coronaviruses have a history of host-shifting.

The sudden appearance and potential lethality of severe acute respiratory syndrome associated coronavirus (SARS-CoV) in humans has focused attention on understanding its origins. Here, we assess phylogenetic relationships for the SARS-CoV lineage as well as the history of host-species shifts for SARS-CoV and other coronaviruses. We used a Bayesian phylogenetic inference approach with sliding window analyses of three SARS-CoV proteins: RNA dependent RNA polymerase (RDRP), nucleocapsid (N) and spike (S). Conservation of RDRP allowed us to use a set of Arteriviridae taxa to root the Coronaviridae phylogeny. We found strong evidence for a recombination breakpoint within SARS-CoV RDRP, based on different, well supported trees for a 5' fragment (supporting SARS-CoV as sister to a clade including all other coronaviruses) and a 3' fragment (supporting SARS-CoV as sister to group three avian coronaviruses). These different topologies are statistically significant: the optimal 5' tree could be rejected for the 3' region, and the optimal 3' tree could be rejected for the 5' region. We did not find statistical evidence for recombination in analyses of N and S, as there is little signal to differentiate among alternative trees. Comparison of phylogenetic trees for 11 known host-species and 36 coronaviruses, representing coronavirus groups 1-3 and SARS-CoV, based on N showed statistical incongruence indicating multiple host-species shifts for coronaviruses. Inference of host-species associations is highly sensitive to sampling and must be considered cautiously. However, current sampling suggests host-species shifts between mouse and rat, chicken and turkey, mammals and manx shearwater, and humans and other mammals. The sister relationship between avian coronaviruses and the 3' RDRP fragment of SARS-CoV suggests an additional host-species shift. Demonstration of recombination in the SARS-CoV lineage indicates its potential for rapid unpredictable change, a potentially important challenge for public health management and for drug and vaccine development.

Animals↗
PubMed2002

A regression-based method to identify differentially expressed genes in microarray time course studies and its application in an inducible Huntington's disease transgenic model.

Time-course studies with microarray technologies provide enormous potential for exploring underlying mechanisms of biological phenomena in many areas of biomedical research, but the large amount of gene expression data generated by such studies also presents great challenges to data analysis. Here we introduce a regression-based statistical modeling approach that identifies differentially expressed genes in microarray time-course studies. To illustrate this method, we applied it to data generated from an inducible Huntington's disease transgenic model. The regression method accounts for the induction process, incorporates relevant experimental information, and includes parameters that specifically address the research interest: the temporal differences in gene expression profiles between the mutant and control mice over the time course, in addition to heterogeneities that commonly exist in microarray data. Least-squares and estimating equation techniques were used to estimate parameters and variances, and inferences were made based on efficient and robust Z-statistics under a set of well-defined assumptions. A permutation test was also used to estimate the number of false-positives, providing an alternative measurement of statistical significance useful for investigators to make decisions on follow-up studies.

Animals↗
PubMed1999

Statistical model building and model criticism for human circadian data.

Mathematical models have played an important role in the analysis of circadian systems. The models include simulation of differential equation systems to assess the dynamic properties of a circadian system and the use of statistical models, primarily harmonic regression methods, to assess the static properties of the system. The dynamical behaviors characterized by the simulation studies are the response of the circadian pacemaker to light, its rate of decay to its limit cycle, and its response to the rest-activity cycle. The static properties are phase, amplitude, and period of the intrinsic oscillator. Formal statistical methods are not routinely employed in simulation studies, and therefore the uncertainty in inferences based on the differential equation models and their sensitivity to model specification and parameter estimation error cannot be evaluated. The harmonic regression models allow formal statistical analysis of static but not dynamical features of the circadian pacemaker. The authors present a paradigm for analyzing circadian data based on the Box iterative scheme for statistical model building. The paradigm unifies the differential equation-based simulations (direct problem) and the model fitting approach using harmonic regression techniques (inverse problem) under a single schema. The framework is illustrated with the analysis of a core-temperature data series collected under a forced desynchrony protocol. The Box iterative paradigm provides a framework for systematically constructing and analyzing models of circadian data.

Adult↗
PubMed1998

Meta-analysis of linkage data under worst-case conditions: a demonstration using the human OB region.

To date, few methods have been developed explicitly for meta-analysis of linkage analyses. Moreover, the methods that have been developed or suggested generally depend on certain ideal situations and have not been widely applied. In this article, we apply standard statistical theory and meta-analytic techniques in novel ways to five published papers discussing the evidence of linkage of body mass index (BMI) to the region of the human genome containing the OB gene. These methods are "inference based," meaning that they allow one to make statements about the statistical significance of the entire body of evidence. As currently developed, they do not allow specific statements to be made about the amount of variance explained by any putative locus or allow precise confidence intervals to be placed around the putative location of a linked locus. By applying these techniques to the literature on linkage in the human OB gene region, we are able to show that the evidence for linkage somewhere in the region is extremely strong (P = 1.5 x 10[-5]).

Body Mass Index↗
PubMed1997

Does diesel exhaust cause human lung cancer?

Recent reviews of epidemiological evidence on the relation between exposure to diesel exhaust (DE) and lung cancer risk have reached conflicting conclusions, ranging from belief that there is sufficient evidence to conclude that DE is a human lung carcinogen (California EPA, 1994) to conclusions that there is inadequate evidence to support a causal association between DE and human lung cancer (Muscat and Wynder, 1995). Individual studies also conflict, with both increases and decreases in relative risks of lung cancer mortality being cited with 95% statistical confidence. On balance, reports of elevated risk outnumber reports of reduced risk. This paper reexamines the evidence linking DE exposures to lung cancer risk. After briefly reviewing animal data and biological mechanisms, it surveys the relevant epidemiological literature and examines possible explanations for the discrepancies. These explanations emphasize the distinction between statistical associations, which have been found in many studies, and causal associations, which appear not to have been established. Methodological threats to valid causal inference are identified and new approaches for controlling them are proposed using recent techniques from artificial intelligence (AI) and computational statistics. These threats have not been adequately controlled for in previous epidemiological studies. They provide plausible noncausal explanations for the reported increases in relative risks, making it impossible to infer causality between DE exposure and lung cancer risk from these studies. A key contribution is to show how recent techniques developed in the AI-and-statistics literature can help clarify the causal interpretation of complex multivariate data sets used in epidemiological risk assessments. Applied to the key study of Garshick et al. (1988), these methods show that DE concentration has no positive causal association with occupational lung cancer mortality risk.

Animals↗
PubMed1997

Hypothesis testing in evolutionary inference.

The comparative method, amongst other things, searches for correlations between evolutionary variables. These can be used to test null hypotheses. Here I consider, in the context of binary variables, the bases of such tests. I examine grounds upon which evolutionary traits and events can be regarded as statistically independent of each other. I argue that no description of observations as independent or non-independent makes sense except in the context of a population of possible observations from which they are regarded as having being sampled. Significant correlations between traits or changes in traits in comparative tests have been taken by some to imply causal links between traits. However, the statistical significance of an observed correlation between traits is neither necessary nor sufficient for the inference of a causal connection between them.

Animals↗
PubMed2006

Farm Scale Evaluations of spring-sown genetically modified herbicide-tolerant crops: a statistical assessment.

Primary results from the Farm Scale Evaluations (FSEs) of spring-sown genetically modified herbicide-tolerant crops were published in 2003. We provide a statistical assessment of the results for count data, addressing issues of sample size (n), efficiency, power, statistical significance, variability and model selection. Treatment effects were consistent between rare and abundant species. Coefficients of variation averaged 73% but varied widely. High variability in vegetation indicators was usually offset by large n and treatment effects, whilst invertebrate indicators often had smaller n and lower variability; overall, achieved power was broadly consistent across indicators. Inferences about treatment effects were robust to model misspecification, justifying the statistical model adopted. As expected, increases in n would improve detectability of effects whilst, for example, halving n would have resulted in a loss of significant results of about the same order. 40% of the 531 published analyses had greater than 80% power to detect a 1.5-fold effect; reducing n by one-third would most likely halve the number of analyses meeting this criterion. Overall, the data collected vindicated the initial statistical power analysis and the planned replication. The FSEs provide a valuable database of variability and estimates of power under various sample size scenarios to aid planning of more efficient future studies.

Agriculture↗
PubMed2005

Analysis of microarray studies performed in the neurosciences.

The application of microarray technology to basic and applied fields of science has been progressing rapidly and broadly since its initial description. The field of neuroscience stands to benefit particularly, as nervous tissue is the most transcriptionally active system within most biological organisms. Moreover, large numbers of cell and animal models have been created that mimic many biochemical and behavioral features of neurological states and diseases. In the present study, data on study designs, tissue sources, technology platforms, bioinformatic tools, and results obtained from 448 published microarray studies were collected. The data were then summarized to determine overall usage statistics of microarrays. Future directions and applications for microarrays in the neurosciences were then inferred from the data analyzed.

Animals↗
PubMed2001

A simple method for statistical analysis of intensity differences in microarray-derived gene expression data.

BACKGROUND: Microarray experiments offer a potent solution to the problem of making and comparing large numbers of gene expression measurements either in different cell types or in the same cell type under different conditions. Inferences about the biological relevance of observed changes in expression depend on the statistical significance of the changes. In lieu of many replicates with which to determine accurate intensity means and variances, reliable estimates of statistical significance remain problematic. Without such estimates, overly conservative choices for significance must be enforced. RESULTS: A simple statistical method for estimating variances from microarray control data which does not require multiple replicates is presented. Comparison of datasets from two commercial entities using this difference-averaging method demonstrates that the standard deviation of the signal scales at a level intermediate between the signal intensity and its square root. Application of the method to a dataset related to the beta-catenin pathway yields a larger number of biologically reasonable genes whose expression is altered than the ratio method. CONCLUSIONS: The difference-averaging method enables determination of variances as a function of signal intensities by averaging over the entire dataset. The method also provides a platform-independent view of important statistical properties of microarray data.

Algorithms↗