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PubMed2004

Non-stationary time series and the robustness of circadian rhythms.

Circadian rhythms are regular oscillations in the value of behavioral and physiological variables of organisms that recur on a daily basis. The purpose of this study was to evaluate the extent of non-stationarity of circadian rhythms over several days, to determine how damaging is the violation of the assumption of stationarity in the analysis of circadian rhythms, and to formalize the concept of "rhythm robustness" as an index of oscillatory ("weak") stationarity. Simulated (computer-generated) and experimental data sets (rhythms of body temperature and running-wheel activity in several rodent species) were analysed. Tests of stationarity based on the variance of the daily means and the variance of the daily variances revealed that most experimental data sets are not stationary. Analysis of linear trends indicated that significant trends are rare in experimental data sets. Although the non-stationarity of the experimental data sets reduced the spectral energy of the Enright periodogram used to assess rhythmicity, detection of circadian rhythmicity was not prevented in any of the rhythmic data sets. The results of the various analyses allow the inference that, after high-frequency noise is filtered out, the value of the periodogram's Q(P) statistic reflects the extent of stationarity of the time series. Thus, the "robustness" of a circadian rhythm (i.e. the magnitude of the empirical Q(P) value as compared to the Q(P) value associated with a perfectly rhythmic time series) can serve as an index of the stationarity of the rhythm.

Analysis of Variance↗
PubMed2006

Inference in ecology and evolution.

Most ecologists and evolutionary biologists continue to rely heavily on null hypothesis significance testing, rather than on recently advocated alternatives, for inference. Here, we briefly review null hypothesis significance testing and its major alternatives. We identify major objectives of statistical analysis and suggest which analytical approaches are appropriate for each. Any well designed study can improve our understanding of biological systems, regardless of the inferential approach used. Nevertheless, an awareness of available techniques and their pitfalls could guide better approaches to data collection and broaden the range of questions that can be addressed. Although we should reduce our reliance on significance testing, it retains an important role in statistical education and is likely to remain fundamental to the falsification of scientific hypotheses.

Bayes Theorem↗
PubMed2000

Accident reduction factors and causal inference in traffic safety studies: a review.

Accident reduction factors are used to predict the change in accident occurrence which a countermeasure can be expected to cause. Since ethical and legal obstacles preclude the use of randomized experiments when evaluating traffic safety improvements, empirical support for the causal effectiveness of accident countermeasures comes entirely from observational studies. Drawing on developments in causal inference initiated by Donald Rubin, it is argued here that the mechanism by which sites are selected for application of a countermeasure should be included as part of a study's data model, and that when important features of the selection mechanism are neglected, existing methods for estimating accident reduction factors become inconsistent. A promising, but neglected, way out of these difficulties lies in developing rational countermeasure selection methods which also support valid causal inference of countermeasure effects.

Accidents, Traffic↗
PubMed2004

The comparative method rules! Codon volatility cannot detect positive Darwinian selection using a single genome sequence.

All established methods for detecting positive selection at the molecular level rely on comparisons between nucleotide sequences. An exceptional method that purports to detect selection on the basis of a single genomic sequence has recently been proposed. This method uses a measure called "codon volatility," defined for each codon as the ratio between the number of nonsynonymous codons that differ from the codon under study at a single nucleotide position and the number of sense codons that differ from the codon under study at a single nucleotide position. Here, we examine various properties of codon volatility and its derivatives and use simulation of evolutionary processes to determine whether they can be used to detect selective pressures. Codons for only four amino acids (glycine, leucine, arginine, and serine) show any variation in codon volatility. Thus, codon volatility is mainly a proxy for amino acid usage, rather than for codon usage, with 65% of all synonymous changes and 27% of all nonsynonymous changes being undetectable by this measure. Genes identified by the volatility method as being subject to positive selection tend to have idiosyncratic amino acid compositions (e.g., they are glycine rich or arginine poor). An additional property of codon volatility is the near zero variance of its mean expectation, which translates into overestimated statistical significance estimates, especially in the absence of corrections for multiple comparisons. A comparison with measures of selection inferred through comparative methodology reveals no relationship between the results of the two methods. Finally, we show that codon volatility can increase in the absence of positive Darwinian selection; that is, increased codon volatility is not indicative of positive selection.

Animals↗
PubMed2000

Error, bias, and long-branch attraction in data for two chloroplast photosystem genes in seed plants.

Sequences of two chloroplast photosystem genes, psaA and psbB, together comprising about 3,500 bp, were obtained for all five major groups of extant seed plants and several outgroups among other vascular plants. Strongly supported, but significantly conflicting, phylogenetic signals were obtained in parsimony analyses from partitions of the data into first and second codon positions versus third positions. In the former, both genes agreed on a monophyletic gymnosperms, with Gnetales closely related to certain conifers. In the latter, Gnetales are inferred to be the sister group of all other seed plants, with gymnosperms paraphyletic. None of the data supported the modern "anthophyte hypothesis," which places Gnetales as the sister group of flowering plants. A series of simulation studies were undertaken to examine the error rate for parsimony inference. Three kinds of errors were examined: random error, systematic bias (both properties of finite data sets), and statistical inconsistency owing to long-branch attraction (an asymptotic property). Parsimony reconstructions were extremely biased for third-position data for psbB. Regardless of the true underlying tree, a tree in which Gnetales are sister to all other seed plants was likely to be reconstructed for these data. None of the combinations of genes or partitions permits the anthophyte tree to be reconstructed with high probability. Simulations of progressively larger data sets indicate the existence of long-branch attraction (statistical inconsistency) for third-position psbB data if either the anthophyte tree or the gymnosperm tree is correct. This is also true for the anthophyte tree using either psaA third positions or psbB first and second positions. A factor contributing to bias and inconsistency is extremely short branches at the base of the seed plant radiation, coupled with extremely high rates in Gnetales and nonseed plant outgroups.

Chloroplasts↗
PubMed2001

Clinical measurement, artifact, and data analysis in dioptric power space.

It appears now to be recognized that traditional clinical representations of astigmatic power, including sphere, cylinder, and axis, in particular, do not lend themselves directly to satisfactory quantitative analysis. For purposes of analysis, the clinical representations need first to be transformed into representations in dioptric power space. It turns out, however, that characteristics of the clinical measurements carried over into dioptric power space can be a source of spurious conclusions reached in such studies. The source of the problem lies in the nature of sphere, cylinder, and axis and in the discreteness (multiples of 0.25 D, usually, in sphere and cylinder and 1 or 5 degrees in axis) of the clinical measurements. As a consequence, scatter plots of clinical measurements in dioptric power space may show patterns and structures, including clusters, arcs, and moiré effects. All the structures are artifacts of the discreteness in sphere, cylinder, and axis; they have no other physical basis. Furthermore, the clinical measurements can show departures from normality that are also purely artifact. By learning to recognize artifact in the scatter plots, the researcher can overcome some of the problems. But because of the assumption of normality underlying many statistical procedures, the problem of distortions in the distributions remains. The distortions may weaken the confidence with which inferences can be made or even lead to erroneous conclusions. The purpose of this paper is to draw attention to the problems of artifact in analyses of clinical data and to suggest ways of overcoming it or avoiding it at least in part.

Artifacts↗
PubMed2004

Maximum entropy and Bayesian data analysis: Entropic prior distributions.

The problem of assigning probability distributions which reflect the prior information available about experiments is one of the major stumbling blocks in the use of Bayesian methods of data analysis. In this paper the method of maximum (relative) entropy (ME) is used to translate the information contained in the known form of the likelihood into a prior distribution for Bayesian inference. The argument is inspired and guided by intuition gained from the successful use of ME methods in statistical mechanics. For experiments that cannot be repeated the resulting "entropic prior" is formally identical with the Einstein fluctuation formula. For repeatable experiments, however, the expected value of the entropy of the likelihood turns out to be relevant information that must be included in the analysis. The important case of a Gaussian likelihood is treated in detail.

Journal Article↗
PubMed1995

Lack of effect of gender and oral contraceptive steroids on the pharmacokinetics of (R)-ibuprofen in humans.

The effects of gender and oral contraceptive steroids on the pharmacokinetics of (R)-ibuprofen were studied in groups of healthy adult males, females and oral contraceptive steroid (OCS) using females. The values of AUC, CLpo, t1/2 and Vss, app did not differ significantly between the groups. Similarly, the percentage unbound of (R)-ibuprofen in pooled plasma from the three groups was not statistically different. Since chiral inversion is the major determinant of (R)-ibuprofen clearance in humans, it may be inferred from these data that gender and OCS have little or no effect on conversion of (R)-ibuprofen to the pharmacologically active S-enantiomer. Moreover, it is unlikely that hormonal factors influence the activity of the human hepatic long-chain fatty-acid:CoA ligase, the enzyme mediating the rate limiting step of (R)-ibuprofen inversion.

Administration, Oral↗
PubMedDate not supplied

Asymptotic analysis of cross-hole hydraulic tests in fractured granite.

Illman and Tartakovsky (2005a, 2005b) developed a new approach for the interpretation of three-dimensional pneumatic well tests conducted in porous or fractured geologic media, which is based on a straight-line analysis of late-time data. We modify this approach to interpret three-dimensional well tests in the saturated zone and use it to analyze the cross-hole hydraulic test data collected in the Full-Scale Engineered Barrier Experiment gallery at the Grimsel Test Site in Switzerland. The equivalent hydraulic conductivity and specific storage obtained from our analysis increase with the radial distance between the centroids of the pumping and monitoring intervals. Since this scale effect is observed from a single test type (cross-hole tests), it is less ambiguous than scale effects typically inferred from laboratory and multiple types of hydraulic tests (e.g., slug, single- and cross-hole tests). The statistical analysis of the estimated hydraulic parameters shows a strong correlation between equivalent hydraulic conductivity and specific storage.

Engineering↗
PubMed2001

16S/23S rRNA intergenic spacer regions for phylogenetic analysis, identification, and subtyping of Bartonella species.

Species of the genus Bartonella are currently recognized in growing numbers and are involved in an increasing variety of human diseases, mainly trench fever, Carrion's disease, bacillary angiomatosis, endocarditis, cat scratch disease, neuroretinitis, and asymptomatic bacteremia. Such a wide spectrum of infections makes it necessary to develop species and strain identification tools in order to perform phylogenetic and epidemiological studies. The 16S/23S rRNA intergenic spacer region (ITS) was sequenced for four previously untested species, B. vinsonii subsp. arupensis, B. tribocorum, B. alsatica, and B. koehlerae, as well as for 28 human isolates of B. quintana (most of them from French homeless people), six human or cat isolates of B. henselae, five cat isolates of B. clarridgeiae, and four human isolates of B. bacilliformis. Phylogenetic trees inferred from full ITS sequences of the 14 recognized Bartonella species using parsimony and distance methods revealed high statistical support, as bootstrap values were higher than those observed with other tested genes. Five well-supported lineages were identified within the genus and the proposed phylogenetic organization was consistent with that resulting from protein-encoding gene sequence comparisons. The ITS-derived phylogeny appears, therefore, to be a useful tool for investigating the evolutionary relationships of Bartonella species and to identify Bartonella species. Further, partial ITS amplification and sequencing offers a sensitive means of intraspecies differentiation of B. henselae, B. clarridgeiae, and B. bacilliformis isolates, as each strain had a specific sequence. The usefulness of this approach in epidemiological investigations should be highlighted. Among B. quintana strains, however, the genetic heterogeneity was low, as only three ITS genotypes were identified. It was nevertheless sufficient to show that the B. quintana population infecting homeless people in France was not clonal.

Animals↗
PubMed2001

Assessing the clinical importance of statistically significant improvement in anti-dementia drug trials.

A strategy for assessing the clinical importance of statistically significant treatment benefits in recent dementia drug trials is proposed. Traditional criteria for the assessment of valid inferences are helpful: the more likely the treatment effects are valid, the greater the chance that they will be clinically important. The role of the Clinician's Interview-Based Impression of Change is also of some importance. Progress in this area faces the special challenge that the 'new' disease entity of partial treatment of Alzheimer's disease has not been well described. Large, systematic clinical studies of treated patients remain necessary to define reliable guides to successful treatment.

Aged↗
PubMed2005

A confidence set inference procedure for gene mapping using markers with incomplete polymorphism.

A recent approach for gene mapping based on confidence set inference (CSI) promises several advantages, including avoidance of corrections for multiple tests, availability of confidence intervals with known statistical properties, and sufficient localizations of disease genes. This paper proposes an extended CSI procedure that can handle markers with incomplete polymorphism, thereby increasing the applicability of the set of CSI methods in practical situations. Simulation studies show that the new procedure retains the main advantages of the original CSI. Although it generally requires more data to achieve a similar power, this increase is moderate for markers with 80% heterozygosity or higher. We also investigate the effects of relative risk estimates and disease models. Our analyses show that perturbation from actual relative risks or multilocus disease models generally leads to reduction in power or inflation in type I error, as expected. Nevertheless, for certain classes of two-locus disease models, CSI can still perform well, with reasonably high actual coverage probabilities for at least one of the disease loci. Application of CSI to the data provided by the Genetic Analysis Workshop 13 yields encouraging results, as they compare favorably to those obtained from GENEHUNTER using its NPL sib-pair method.

Chromosome Mapping↗
PubMedDate not supplied

The role of reported primary race on health measures for multiple race respondents in the National Health Interview Survey.

OBJECTIVES: As data for multiple race groups have only recently been collected and tabulated, the current understanding of the health of multiple race groups is not well developed. In the National Health Interview Survey (NHIS), survey respondents who report more than one race are asked to identify a primary race. This report compares selected health and demographic measures by the response to the primary race question and compares estimates for specific primary race groups to corresponding estimates for single race groups. METHODS: Using 1997-2003 NHIS data, several demographic and health measures were compared by reported primary race within the four largest multiple race groups. Then estimates by primary race for these four multiple race groups were compared to those for their single race counterparts. RESULTS: There were few statistically significant associations between reported primary race and health or demographic variables within the four multiple race groups. This lack of association may be due to the small number of multiple race respondents (which results in large standard errors) rather than similarity of point estimates among the subgroups. A greater number of differences between estimates for single race groups and for multiple race respondents who reported the same single race as their primary race were identified. CONCLUSIONS: The apparent lack of association between primary race within a multiple race group and health outcomes suggests that tabulating multiple race responses by primary race is unnecessary for valid health estimates for multiple race groups, at least with available statistical power. However, differences between single race and primary race estimates within a multiple race group suggest that inferences for multiple race respondents using single race estimates may be imprecise for some outcomes.

Adolescent↗
PubMed2004

Methodologic and statistical approaches to studying human fertility and environmental exposure.

Although there has been growing concern about the effects of environmental exposures on human fertility, standard epidemiologic study designs may not collect sufficient data to identify subtle effects while properly adjusting for confounding. In particular, results from conventional time to pregnancy studies can be driven by the many sources of bias inherent in these studies. By prospectively collecting detailed records of menstrual bleeding, occurrences of intercourse, and a marker of ovulation day in each menstrual cycle, precise information on exposure effects can be obtained, adjusting for many of the primary sources of bias. This article provides an overview of the different types of study designs, focusing on the data required, the practical advantages and disadvantages of each design, and the statistical methods required to take full advantage of the available data. We conclude that detailed prospective studies allowing inferences on day-specific probabilities of conception should be considered as the gold standard for studying the effects of environmental exposures on fertility.

Data Collection↗
PubMed2003

Fiber-assisted detection with photon number resolution.

We report the development of a photon-number-resolving detector based on a fiber-optical setup and a pair of standard avalanche photodiodes. The detector is capable of resolving individual photon numbers and operates on the well-known principle by which a single-mode input state is split into a large number (eight) of output modes. We reconstruct the photon statistics of weak coherent input light from experimental data and show that there is a high probability of inferring the input photon number from a measurement of the number of detection events on a single run.

Journal Article↗