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Estimating pairwise relatedness from dominant genetic markers.

Knowledge of the genetic relatedness between a pair of individuals is important in many research areas of quantitative genetics, conservation genetics, evolution and ecology. Many estimators have been developed to estimate such pairwise relatedness (r) using codominant markers, such as microsatellites and enzymes. In contrast, only two estimators are proposed to use dominant markers, such as random amplified polymorphic DNAs (RAPDs) and amplified fragment length polymorphisms (AFLPs), in relatedness inference. They are both biased estimators, and their statistical properties and robustness to the sampling errors in allele frequency have not been investigated. In this short paper, I propose two new pairwise relatedness estimators for dominant markers, and compare them in precision, accuracy and robustness to sampling with the two previous estimators using simulations. It was found that the new estimator based on the least squares approach is unbiased when allele frequencies are known or estimated from a sample without correcting for sampling effects. It has, however, a low precision and as a result, an intermediate overall performance among the four estimators in terms of the mean squared deviation (MSD) of estimates from actual values of r. The new estimator based on a similarity index is slightly biased but has generally the lowest MSD among the four estimators compared, regardless of the number of loci, type of actual relationships, allele frequencies known or estimated from samples. Simulations also show that the confidence intervals estimated by bootstrapping are appropriate for different estimators provided that the number of loci used in the estimation is not small.

Computer Simulation↗

Exact two-sample inference with missing data.

When comparing follow-up measurements from two independent populations, missing records may arise due to censoring by events whose occurrence is associated with baseline covariates. In these situations, inferences based only on the completely followed observations may be biased if the follow-up measurements and the covariates are correlated. This article describes exact inference for a class of modified U-statistics under covariate-dependent dropouts. The method involves weighing each permutation according to the retention probabilities, and thus requires estimation of the missing data mechanism. The proposed procedure is nonparametric in that no distributional assumption is necessary for the outcome variables and the missingness patterns. Monte Carlo approximation by the Gibbs sampler is proposed, and is shown to be fast and accurate via simulation. The method is illustrated in two small data sets for which asymptotic inferential procedures may not be appropriate.

Biometry↗

Multi-state models for event history analysis.

An introduction to event history analysis via multi-state models in given. Examples include the two-state model for survival analysis, the competing risks and illness-death models, and models for bone marrow transplantation. Statistical model specification via transition intensities and likelihood inference is introduced. Consequences of observational patterns are discussed, and a real example concerning mortality and bleeding episodes in a liver cirrhosis trial is discussed.

Biometry↗

[Sampling and representativeness in epidemiological surveillance using sentinel sites]

This article maintains that technical issues for sampling in epidemiological surveillance require a profound review of important concepts from health theory. It is particularly neccessary to emphasize living conditions and more specifically the environments or contexts in which reproductive processes of social life take place. However, both fields require access to more complete data than those produced by traditional sources. Such an approach to epidemiological surveillance requires a review of sampling types, and this implies a new look at prevailing interpretations concerning the logical basis for inferences from samples. It becomes necessary to abandon statistical samples (even stratified ones) and to promote procedures of the "sentinel site" type. This techinique, originally applied in societies with insufficient statistical systems, can be developed in such a way as to become a substantial complement to monitoring of living conditions, even in societies with good information systems. The article suggests changes in the "sentinel site" concept, adding the requirement of "qualitative representativeness" through finalistic samples based on previous typologies of spatial/demographic units.

Journal Article↗

An approach for measuring methane emissions from whole farms.

Estimates of enteric methane (CH4) emissions from ruminants are typically measured by confining animals in large chambers, using head hoods or masks, or by a ratiometric technique involving sampling respired air of the animal. These techniques are not appropriate to evaluate large-scale farm emissions and the variability between farms that may be partly attributed to different farm management. This study describes the application of an inverse-dispersion technique to calculate farm emissions in a controlled tracer-release experiment. Our study was conducted at a commercial dairy farm in southern Alberta, Canada (total of 321 cattle, including 152 lactating dairy cows). Sulfur hexafluoride (SF6) and CH4 were released from 10 outlet locations (barn and open pens) using mass-flow controllers. A Lagrangian stochastic (LS) dispersion model was then used to infer farm emissions from downwind gas concentrations. Concentrations of SF6 and CH4 were measured by gas chromatography analysis and open path lasers, respectively. Wind statistics were measured with a three-dimensional sonic anemometer. Comparing the inferred emissions with the known release rate showed we recovered 86% of the released CH4 and 100% of the released SF6. The location of the concentration observations downwind of the farm was critically important to the success of this technique.

Animals↗

[New functional cerebral cartography: studies of plasticity of the human brain].

The non-invasive brain scanning techniques, introduced a quarter of a century ago, have become crucial for diagnosis in clinical neurology. They have also been used to investigate brain function and have provided information about normal activity and pathogenesis. They have been used to investigate functional specialisation in the brain and how specialised areas communicate to generate complex integrated functions such as speech, memory, the emotions and so on. Brain plasticity is a generic term that has now come to be used to signify any changes in brain structure or function. The phenomenon is poorly understood, and yet clinical neurologists are aware that spontaneous recovery from brain lesions is not uncommon. An improved understanding of the mechanisms of recovery may generate new therapeutic strategies and indicate ways of modulating mechanisms that promote plastic compensation for loss of function. The main methods used to investigate these issues are positron emission tomography and magnetic resonance imaging (MRI). The techniques of functional brain mapping and computational morphometrics depend on high performance scanners and a validated set of analytic statistical procedures that generate reproducible data and meaningful inferences from them. The motor system presents a good paradigm to illustrate advances made by scanning towards an understanding of plasticity at the level of brain areas. The normal motor system is organised in a nested hierarchy. Recovery from paralysis caused by internal capsule strokes involves functional reorganisation manifesting as changed patterns of activity in the component brain areas of the normal motor system. The pattern of plastic modification depends in part on patterns of residual or disturbed connectivity after brain injury. Therapeutic manipulations in patients with Parkinson's disease using deep brain stimulation, dopaminergic agents or foetal mesencephalic transplantation provide a means to examine mechanisms underpinning plastic change. Other models of plastic change, such as normal visuospatial learning or re-establishing speech comprehension after cochlear implantation in the deaf illustrate how patterns of brain function adapt over time. Limitations of the scanning techniques and prospects for the future are discussed in relation to new developments in the neuroimaging field.

Brain↗

[Healthy nutrition and the prevention of cancer].

A number of risk factors of cancer diseases can be identified in the diet of the Hungarian population, and also one may infer the presence of these risk factors from statistics on food purchasing, the results of household budget surveys and those of earlier nutrition surveys. These risk factors are: overweight and obesity involving two thirds of the male and half of the female population, insufficient vegetable and fruit consumption, insufficient wholemeal cereal consumption, inadequate dietary fibre intake, high sugar intake, regular heavy drinking, as well as high fat, animal fat, cholesterol and salt intakes. The messages for decreasing the risks of cancer diseases--as presented herein--have been included in the recommendations for healthy nutrition aimed at eliminating the risk factors of diet-related diseases.

Alcohol Drinking↗

Forthergillian Lecture. Imaging human brain function.

The non-invasive brain scanning techniques introduced a quarter of a century ago have become crucial for diagnosis in clinical neurology. They have also been used to investigate brain function and have provided information about normal activity and pathogenesis. They have been used to investigate functional specialization in the brain and how specialized areas communicate to generate complex integrated functions such as speech, memory, the emotions and so on. The phenomenon of brain plasticity is poorly understood and yet clinical neurologists are aware, from everyday observations, that spontaneous recovery from brain lesions is common. An improved understanding of the mechanisms of recovery may generate new therapeutic strategies and indicate ways of modulating mechanisms that promote plastic compensation for loss of function. The main methods used to investigate these issues are positron emission tomography and magnetic resonance imaging (M.R.I.). M.R.I. is also used to map brain structure. The techniques of functional brain mapping and computational morphometrics depend on high performance scanners and a validated set of analytic statistical procedures that generate reproducible data and meaningful inferences from brain scanning data. The motor system presents a good paradigm to illustrate advances made by scanning towards an understanding of plasticity at the level of brain areas. The normal motor system is organized in a nested hierarchy. Recovery from paralysis caused by internal capsule strokes involves functional reorganization manifesting itself as changed patterns of activity in the component brain areas of the normal motor system. The pattern of plastic modification depends in part on patterns of residual or disturbed connectivity after brain injury. Therapeutic manipulations in patients with Parkinson's disease using deep brain stimulation, dopaminergic agents or fetal mesencephalic transplantation provide a means to examine mechanisms underpinning plastic change. Other models of plastic change, such as normal visuospatial learning or re-establishing speech comprehension after cochlear implantation in the deaf illustrate how patterns of brain function adapt over time. Limitations of the scanning techniques and prospects for the future are discussed in relation to new developments in the neuroimaging field.

Brain↗

[Language development in adolescence: semantic, syntactic and pragmatic competences].

BACKGROUND: Low learning rates during adolescence can be associated to deficits in language processing. AIM: To characterize the performance of adolescents, with and without complaints in metalinguistic tasks, and to verify the applicability of 4 subtests of the Test of Language Competence-Expanded (TLC-E) (Wiig & Secord, 1985; 1989). METHOD: 16 students with ages between 16 and 18 years were assessed, 8 with learning difficulties and 8 with no learning difficulties. The TLC-E was used, which assess the understanding of language ambiguity, inference, figurative language, syntactic elaboration and memory. RESULTS: Statistic differences were observed in the performance of both groups in all of the used subtests. CONCLUSION: It can be concluded that the group with learning difficulties presented a lower performance than the group with no learning difficulties, and that the used instrument was able to distinguish both groups.

Adolescent↗

Case-control studies.

This paper will provide an overview of the case-control study including the definition, types of study design, advantages and disadvantages, potential types and sources of bias, selection of controls, statistical measures of association, and criteria for suggesting inferences about causation. Measures of association for HLA-B27 and ankylosing spondylitis (AS) and HLA-DR4 and rheumatoid arthritis (RA) are calculated from previously published data. Case-control studies are useful for identifying etiologic associations in uncommon diseases.

Arthritis, Rheumatoid↗

[The use of continuous epidural analgesia in the combined treatment of chronic arterial obstruction in the lower extremities].

Experience had with the application of continuous epidural analgesia (CEDA) in the complex treatment of 33 patients with advanced stage of chronic arterial obstruction in the lower extremities is presented. In fourteen of them (42.4 per cent) CEDA is effected using implantable catheterization system "Periplant", and in the remainder 19 (57.6 per cent)--through nonimplantable "Periflex++". The technique of application of the systems is described. The therapeutic effect is estimated on the basis of: 1) quantitative evaluation of pain perception by a 5-point rating system, 2) acral skin thermometry, and 3) Doppler ultrasound tonometry. Changes in the parameters listed are compared with their counterparts in a control group of 33 patients, and subjected to statistical processing. Proceeding from the obtained results the inference is reached that CEDA is very effective in terms of main relief, and improves perfusion of the ischemic limbs. The implantable catheterization systems contribute to the patient's comfort for rather prolonged period of time, and reduce infection hazards in the vicinity of the spinal cord.

Aged↗

An example of using mixed models and PROC MIXED for longitudinal data.

Longitudinal data, or data that are repeated measurements on various subjects across time, are commonplace in biostatistical studies. The general linear mixed model is a useful statistical tool for analyzing such data and drawing meaningful inferences about them. This paper discusses some of the most common mixed models and fits them to a prototypical example involving repeated measures on blood pressure. Computer implementation is via the MIXED procedure in the SAS System, and code descriptions and output interpretations accompany the example.

Clinical Trials as Topic↗

Appropriate statistical methods to account for similarities in binary outcomes between fellow eyes.

PURPOSE: Many ocular measurements are more alike between fellow eyes than between eyes from different individuals. To make appropriate inferences using data from both eyes rather than the best or worst eye, statistical methods that account for the association between fellow eyes must be used. METHODS: Marginal and conditional regression models account for the association between fellow eyes in different ways. The authors compare and contrast these methods using data from a series of patients with retinitis pigmentosa in whom the primary object is to identify risk factors, some of which are subject specific and some of which are eye specific, for visual acuity loss (as a binary outcome) among affected subjects. RESULTS: Odds ratios for age, gender, presence of posterior subcapsular cataract, and genetic type of retinitis pigmentosa obtained from the marginal model were all larger than those from the conditional model. Familial aggregation of visual acuity loss was statistically significant in the marginal, but not in the conditional, model. CONCLUSIONS: The estimates and interpretation of the association between an ocular outcome and risk factors can differ significantly between these two approaches. The choice of model depends on the scientific questions of interest rather than on statistical considerations. Computer programs are available for implementing both models.

Baltimore↗

The incremental validity of psychological testing and assessment: conceptual, methodological, and statistical issues.

There has been insufficient effort in most areas of applied psychology to evaluate incremental validity. To further this kind of validity research, the authors examined applicable research designs, including those to assess the incremental validity of test instruments, of test-informed clinical inferences, and of newly developed measures. The authors also considered key statistical and measurement issues that can influence incremental validity findings, including the entry order of predictor variables, how to interpret the size of a validity increment, and possible artifactual effects in the criteria selected for incremental validity research. The authors concluded by suggesting steps for building a cumulative research base concerning incremental validity and by describing challenges associated with applying nomothetic research findings to individual clinical cases.

Humans↗

Nonlinear statistical modeling and model discovery for cardiorespiratory data.

We present a Bayesian dynamical inference method for characterizing cardiorespiratory (CR) dynamics in humans by inverse modeling from blood pressure time-series data. The technique is applicable to a broad range of stochastic dynamical models and can be implemented without severe computational demands. A simple nonlinear dynamical model is found that describes a measured blood pressure time series in the primary frequency band of the CR dynamics. The accuracy of the method is investigated using model-generated data with parameters close to the parameters inferred in the experiment. The connection of the inferred model to a well-known beat-to-beat model of the baroreflex is discussed.

Algorithms↗

MEGA: Molecular Evolutionary Genetics Analysis software for microcomputers.

A computer program package called MEGA has been developed for estimating evolutionary distances, reconstructing phylogenetic trees and computing basic statistical quantities from molecular data. It is written in C++ and is intended to be used on IBM and IBM-compatible personal computers. In this program, various methods for estimating evolutionary distances from nucleotide and amino acid sequence data, three different methods of phylogenetic inference (UPGMA, neighbor-joining and maximum parsimony) and two statistical tests of topological differences are included. For the maximum parsimony method, new algorithms of branch-and-bound and heuristic searches are implemented. In addition, MEGA computes statistical quantities such as nucleotide and amino acid frequencies, transition/transversion biases, codon frequencies (codon usage tables), and the number of variable sites in specified segments in nucleotide and amino acid sequences. Advanced on-screen sequence data and phylogenetic-tree editors facilitate publication-quality outputs with a wide range of printers. Integrated and interactive designs, on-line context-sensitive helps, and a text-file editor make MEGA easy to use.

Algorithms↗

Single subject image analysis using the complex general linear model--an application to functional magnetic resonance imaging with multiple inputs.

A linear time invariant model is applied to functional fMRI blood flow data. Based on traditional time series analysis, this model assumes that the fMRI stochastic output sequence can be determined by a constant plus a linear filter (hemodynamic response function) of several fixed deterministic inputs and an error term assumed stationary with zero mean. The input function consists of multiple exponential distributed (time delay between images) visual stimuli consisting of negative and erotic images. No a priori assumptions are made about the hemodynamic response function that, in essence, is calculated at each spatial position from the data. The sampling rate for the experiment is 400 ms in order to allow for filtering out higher frequencies associated with the cardiac rate. Since the statistical analysis is carried out in the Fourier domain, temporal correlation problems associated with inference in the time domain are avoided. This formal model easily lends itself to further development based on previously developed statistical techniques.

Adult↗

The (mis)estimation of neighborhood effects: causal inference for a practicable social epidemiology.

The resurgence of interest in the effect of neighborhood contexts on health outcomes, motivated by advances in social epidemiology, multilevel theories and sophisticated statistical models, too often fails to confront the enormous methodological problems associated with causal inference. This paper employs the counterfactual causal framework to illuminate fundamental obstacles in the identification, explanation, and usefulness of multilevel neighborhood effect studies. We show that identifying useful independent neighborhood effect parameters, as currently conceptualized with observational data, to be impossible. Along with the development of a dependency-based methodology and theories of social interaction, randomized community trials are advocated as a superior research strategy, one that may help social epidemiology answer the causal questions necessary for remediating disparities and otherwise improving the public's health.

Bias↗