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Results for “statistical inference”

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At least 631 records · Page 35Linked to original sources
PubMed1996

The effects of exposure to "synthetic" chemicals on human health: a review.

This article examines how scientists use human, animal, and bacterial evidence to develop policy recommendations about the health consequences of human exposure to modern chemicals. Human evidence is limited because many epidemiological studies are contaminated with selection effects or unobserved heterogeneity. Changes in the aggregate incidence of morbidity (such as cancer) in the population over time are not a substitute for the lack of good individual-level data because incidence data are contaminated by the medicalization of cancer. Animal tests are also problematic because the expense of conducting experiments leads researchers to use only enough animals to allow detection of large differences in cancer incidence between controls and experimental animals that can only arise if the exposure doses are large. Predictions about the cancer incidence that would result in humans at much lower exposure levels, thus, require statistical inferences that implicitly make choices between false positive and false negative inference errors. Policy recommendations about carcinogens, therefore, are as much the product of value choices as "scientific" knowledge.

Animal Testing Alternatives↗
PubMed1997

Projection of health benefits from ambient ozone reduction related to the use of methyl tertiary butyl ether (MTBE) in the reformulated gasoline program.

To estimate potential public health benefits from ozone (O3) pollution reduction attributable to the use of methyl tertiary-butyl ether (MTBE) in gasoline, O3 dose-response estimates from the biomedical literature were combined with model estimates of O3 reduction. Modeling employed EPA MOBILE5a and Complex models to predict emission changes, industry AQIRP techniques to predict ambient O3 changes, and the National Exposure Model to predict human exposures. Human health effects considered were lung function decrements and respiratory irritant symptoms (using dose-response functions measured in laboratory and field studies), and increased death rates (using concentration-response functions inferred statistically from public-health data). Other reported health effects, such as lung inflammation, increases in asthma attacks, and hospitalizations, were not addressed because of inadequate dose-response information. Even for the health responses considered, quantitation of improvements due to MTBE use is problematical, because MTBE affects only a small percentage of existing O3 pollution, and because exposure-response relationships are not well understood for population subgroups most likely to be affected. Nevertheless, it is reasonable to conclude that even small MTBE-associated reductions in peak ambient O3 levels (1-5 ppb, according to model estimates) should yield considerable public health benefits. Tens of millions of Americans are potentially exposed to O3 in the concentration range associated with health effects. Even if only a small percentage of them are susceptible, any incremental reduction in O3 (as with MTBE use) must mitigate or prevent effects for a meaningful number of people. Better quantitative estimates of benefit must await a more detailed understanding of each link in the chain of causation.

Air Pollutants↗
PubMed2002

Genetic diversity and models of viral evolution for the hepatitis C virus.

In this review we discuss the application of theoretical frameworks to the interpretation of viral gene sequence data, with particular reference to the hepatitis C virus (HCV). The increasing availability of such data means that it is now possible (and necessary) to proceed from simple qualitative models of viral evolution, to more quantitative frameworks based on statistical inference, notably population genetics and molecular phylogenetics. We argue that these approaches are invaluable tools to the virologist and are essential for understanding the dynamics of viral infection and the outcome of therapeutic strategies. We use several recent HCV data-sets to illustrate the methods.

Genetic Variation↗
PubMed1991

Nonparametric estimation of phase variance in auditory-nerve fiber's responses to tonal stimuli.

Statistical estimation of the phase variance from the auditory-nerve fiber's action potential timing data is studied in this paper. A detailed derivation of the sample-based estimation formulas, which deals specifically with the circularity of the phase variable, is given. The development of the estimator is based on nonparametric statistical inference techniques, making no assumptions on the parametric form of the phase distribution (i.e., shape of period histogram). Some desirable properties of the estimator are demonstrated through numerical examples and applications of the estimator in auditory research are discussed.

Acoustic Stimulation↗
PubMed1985

Gene density over the chromosome of Escherichia coli: frequency distribution, spatial clustering, and symmetry.

Published studies of gene density (the number of genetic loci per unit of length on the linkage map) for Escherichia coli report a nonrandom frequency distribution and indicate notable symmetry in spatial clustering of gene density. We reexamined these results and found that gene density is a random variable with a frequency distribution that is lognormal. That is, the logarithm of gene density is a normally distributed random variable. Furthermore, comparison of the observed E. coli map and computer-generated random maps showed that symmetries in the spatial clustering of gene density are not exceptional; these features arise naturally among genes (or loci) whose density has this frequency distribution. These results are discussed along with other related examples that illustrate the emerging importance of statistical inference in molecular genetics.

Bacterial Proteins↗
PubMed2000

Empirical assessment of effect of publication bias on meta-analyses.

OBJECTIVE: To assess the effect of publication bias on the results and conclusions of systematic reviews and meta-analyses. DESIGN: Analysis of published meta-analyses by trim and fill method. STUDIES: 48 reviews in Cochrane Database of Systematic Reviews that considered a binary endpoint and contained 10 or more individual studies. MAIN OUTCOME MEASURES: Number of reviews with missing studies and effect on conclusions of meta-analyses. RESULTS: The trim and fill fixed effects analysis method estimated that 26 (54%) of reviews had missing studies and in 10 the number missing was significant. The corresponding figures with a random effects model were 23 (48%) and eight. In four cases, statistical inferences regarding the effect of the intervention were changed after the overall estimate for publication bias was adjusted for. CONCLUSIONS: Publication or related biases were common within the sample of meta-analyses assessed. In most cases these biases did not affect the conclusions. Nevertheless, researchers should check routinely whether conclusions of systematic reviews are robust to possible non-random selection mechanisms.

Clinical Trials as Topic↗
PubMed2004

Comparative genomic hybridisation using a proximal 17p BAC/PAC array detects rearrangements responsible for four genomic disorders.

BACKGROUND: Proximal chromosome 17p is a region rich in low copy repeats (LCRs) and prone to chromosomal rearrangements. Four genomic disorders map within the interval 17p11-p12: Charcot-Marie-Tooth disease type 1A, hereditary neuropathy with liability to pressure palsies, Smith-Magenis syndrome, and dup(17)(p11.2p11.2) syndrome. While 80-90% or more of the rearrangements resulting in each disorder are recurrent, several non-recurrent deletions or duplications of varying sizes within proximal 17p also have been characterised using fluorescence in situ hybridisation (FISH). METHODS: A BAC/PAC array based comparative genomic hybridisation (array-CGH) method was tested for its ability to detect these genomic dosage differences and map breakpoints in 25 patients with recurrent and non-recurrent rearrangements. RESULTS: Array-CGH detected the dosage imbalances resulting from either deletion or duplication in all the samples examined. The array-CGH approach, in combination with a dependent statistical inference method, mapped 45/46 (97.8%) of the analysed breakpoints to within one overlapping BAC/PAC clone, compared with determinations done independently by FISH. Several clones within the array that contained large LCRs did not have an adverse effect on the interpretation of the array-CGH data. CONCLUSIONS: Array-CGH is an accurate and sensitive method for detecting genomic dosage differences and identifying rearrangement breakpoints, even in LCR-rich regions of the genome.

Centromere↗
PubMed2024

Causal Mediation Analysis for Integrating Exposure, Genomic, and Phenotype Data.

Causal mediation analysis provides an attractive framework for integrating diverse types of exposure, genomic, and phenotype data. Recently, this field has seen a surge of interest, largely driven by the increasing need for causal mediation analyses in health and social sciences. This article aims to provide a review of recent developments in mediation analysis, encompassing mediation analysis of a single mediator and a large number of mediators, as well as mediation analysis with multiple exposures and mediators. Our review focuses on the recent advancements in statistical inference for causal mediation analysis, especially in the context of high-dimensional mediation analysis. We delve into the complexities of testing mediation effects, especially addressing the challenge of testing a large number of composite null hypotheses. Through extensive simulation studies, we compare the existing methods across a range of scenarios. We also include an analysis of data from the Normative Aging Study, which examines DNA methylation CpG sites as potential mediators of the effect of smoking status on lung function. We discuss the pros and cons of these methods and future research directions.

causal inference↗
PubMed2006

Complete functional characterization of sensory neurons by system identification.

System identification is a growing approach to sensory neurophysiology that facilitates the development of quantitative functional models of sensory processing. This approach provides a clear set of guidelines for combining experimental data with other knowledge about sensory function to obtain a description that optimally predicts the way that neurons process sensory information. This prediction paradigm provides an objective method for evaluating and comparing computational models. In this chapter we review many of the system identification algorithms that have been used in sensory neurophysiology, and we show how they can be viewed as variants of a single statistical inference problem. We then review many of the practical issues that arise when applying these methods to neurophysiological experiments: stimulus selection, behavioral control, model visualization, and validation. Finally we discuss several problems to which system identification has been applied recently, including one important long-term goal of sensory neuroscience: developing models of sensory systems that accurately predict neuronal responses under completely natural conditions.

Animals↗
PubMed1987

Delayed or accelerated oxygen uptake kinetics in the transition from prior exercise?

Reported experimental findings are at variance with each other on the question as to whether O2 uptake (VO2) kinetics are delayed, advanced, or remain unaltered in the transition from prior exercise. Critical examination of these studies tend to suggest that not a great deal of reliance can be placed on their evidence in attempting to resolve the question. They seem to display a disregard for the theoretical properties of the VO2 kinetic model used; in some cases incorrect statistical inferences appear to have been made; most are mathematically incomplete; and the experimental designs have not been appropriately chosen so as to examine the whole question of altered VO2 kinetics. These points are detailed and discussed so that future designed experiments obtain sufficient reliable evidence with which to resolve the question.

Kinetics↗
PubMed1999

Litter effects on caries in rats and implications for experimental design.

The purpose of this study was to obtain quantitative estimates of litter effects on caries development in rats and to examine the implications for design of rat caries experiments. Twelve female Sprague-Dawley rats, aged 60 days, were bred with 4 male rats. Nine of the 12 dams had litters in close proximity. The litters were culled to 10 pups. One pup from each litter was placed with each of the other dams for nursing, leaving 2 pups from each litter with the birth dam. This design allowed the litter effect to be separated into a prenatal component, reflecting the shared genetic makeup and in utero environment of littermates, and a postnatal component reflecting a shared environment from shortly after birth to weaning. Pups were infected with Streptococcus sobrinus and fed Diet 2000 and 10% (w/v) sucrose water for 5 weeks. There was no significant evidence of a postnatal litter effect for smooth surface caries (p = 0.37) or sulcal caries (p = 0.43). The prenatal litter effect was significant for both smooth surface caries and sulcal caries (p<0. 01). When litter effects are present, the statistical power of caries studies is improved if animals from the same litter are divided evenly among experimental groups. In addition, if litter effects are present but not allowed for in data analysis, incorrect statistical inferences may be drawn. Based on our results and other reports of litter effects, we recommend planning for litter effects in the design and analysis of rat caries studies.

Animals↗
PubMed1981

Pulmonary changes during marathon training: a longitudinal study.

The purposes of this study were (1) to confirm whether there were any differences between observed and predicted scores based on age, height, and sex in forced vital capacity (FVC), 1-second forced expiratory volume (FEV1.0), FEV1.0/FVC ratio, functional residual capacity (FRC), total lung capacity (TLC, FRC/TLC ratio, residual volume (RV), RV/TLC ratio, diffusing capacity of lungs for carbon monoxide (DCO), alveolar-capillary permeability (k'CO), and alveolar volume (VA) for 2 middle-aged non-smoking men who trained for and competed in three annual 26.2-mile marathon races and (2) to determine the magnitude and direction of changes in the observed scores for the three annual tests. The subjects trained from 45 to 70 miles/week for 52 weeks during the 3-year period. In the week after their annual marathon run they were measured in the above pulmonary variables. For the 3-year period of training subject A improved five pulmonary variables (TLC, FRC, FRC/TLC ratio, DCO, and k'CO) and had small decreases in function of the other six variables. Likewise, subject B improved three pulmonary variables (FRC, FRC/TLC ratio, and k'CO) and had small decreases in function of the other eight variables. It is not possible to draw statistical inferences to other populations from this data, but it does indicate that these subjects are in a state of good-to-great pulmonary health. Although random variations may account for some of the changes for these 2 subjects, it is possible that marathon training has inhibited some of the deterioration in pulmonary function as predicted from the regression with age by Kory.

Adult↗
PubMed1991

A prospective study of sodium-lithium countertransport and hypertension in Utah.

A 7-year prospective study of a cohort of 1,458 normotensive adults from Utah pedigrees, screened from 1980 to 1985, was done to determine whether baseline levels of sodium-lithium countertransport were associated with an increased risk of future hypertension. Subsequent new hypertension (n = 39) was ascertained in 1989 from detailed follow-up medical questionnaires (67% response). Previous segregation analyses on a subset of these pedigree members who responded (n = 342) using family relationships in addition to countertransport levels have shown statistically inferred major gene segregation of sodium-lithium countertransport levels. In the normotensive adults inferred by segregation analysis to carry the recessive major gene for high sodium-lithium countertransport, new-onset hypertension occurred in 18.8% (3 of 16) compared with 3.7% (12 of 326) in the low sodium-lithium countertransport genotype group (relative risk, 4.6 [1.6, 13.9]; p = 0.03). However, an elevated baseline sodium-lithium countertransport level without genotype information from segregation analysis did not increase the risk of future hypertension in the complete cohort of adult pedigree members (relative risk, 1.02 [0.85, 1.22]). Adjustment for other risk factors reduced the relative risk to 0.90 (0.72, 1.11). We conclude that the presence of a major gene for sodium-lithium countertransport or another closely linked gene, rather than the actual level of sodium-lithium countertransport, may increase the risk of hypertension onset. High sodium-lithium countertransport levels do not increase the risk of future hypertension for individuals in whom only polygenic and environmental effects determine sodium-lithium countertransport level.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

The Helmholtz machine.

Discovering the structure inherent in a set of patterns is a fundamental aim of statistical inference or learning. One fruitful approach is to build a parameterized stochastic generative model, independent draws from which are likely to produce the patterns. For all but the simplest generative models, each pattern can be generated in exponentially many ways. It is thus intractable to adjust the parameters to maximize the probability of the observed patterns. We describe a way of finessing this combinatorial explosion by maximizing an easily computed lower bound on the probability of the observations. Our method can be viewed as a form of hierarchical self-supervised learning that may relate to the function of bottom-up and top-down cortical processing pathways.

Algorithms↗
PubMed2005

Meta-analysis: a case study.

This article raises some questions about the usefulness of meta-analysis as a means of reviewing quantitative research in the social sciences. When a meta-analytic model for SAT coaching is used to predict results from future studies, the amount of prediction error is quite large. Interpretations of meta-analytic regressions and quantifications of program and study characteristics are shown to be equivocal. The match between the assumptions of the meta-analytic model and the data from SAT coaching studies is not good, making statistical inferences problematic. Researcher subjectivity is no less problematic in the context of a meta-analysis than in a narrative review.

Adolescent↗
PubMed2005

Evaluation of a new antibody-based enzyme-linked immunosorbent assay for the detection of bovine leukemia virus infection in dairy cattle.

The objective of this study was to validate a new blocking enzyme-linked immunosorbent assay (ELISA) (designated M108 for milk and S108 for serum samples) for detecting bovine leukemia virus (BLV) infection in dairy cattle. Milk, serum, and ethylenediaminetetraacetic acid-blood samples were collected from 524 adult Holstein cows originating from 6 dairy herds in Central Argentina. The M108 and S108 were compared with agar gel immunodiffusion (AGID), polymerase chain reaction and a commercial ELISA. Because there is currently no reference test capable of serving as a gold standard, the test sensitivity (SE) and specificity (SP) were evaluated by the use of a latent class model. Statistical inference was performed by classical maximum likelihood and by Bayesian techniques. The maximum-likelihood analysis was performed assuming conditional independence of tests, whereas the Bayesian approach allowed for conditional dependence. No clear conclusion could be drawn about conditional dependence of tests. Results with maximum likelihood (under conditional independence) and posterior Bayes (under conditional dependence) were practically the same. Conservative estimates of SE and SP (with 95% confidence intervals) for M108 were 98.6 (96.7; 99.6) and 96.7 (92.9; 98.8) and for S108 99.5 (98.2; 99.9) and 95.4 (90.9; 98.1), respectively. The ELISA 108 using either milk or serum to detect BLV-infected animals had comparable SE and SP with the official AGID and a commercial ELISA test, which are currently the most widely accepted tests for the serological diagnosis of BLV infection. Therefore, ELISA 108 can be used as an alternative test in monitoring and control programs.

Animals↗
PubMed2004

Cortical activation resulting from painless vibrotactile dental stimulation measured by functional magnetic resonance imaging (FMRI).

There have been few investigations on hemodynamic responses in the human cortex resulting from dental stimulation. Identification of cortical areas involved in stimulus perception may offer new targets for pain treatment. This initial study aimed at establishing a cortical map of dental representation, based on non-invasive fMRI measurements. Five right-handed subjects were studied. Eight maxillary and 8 mandibular teeth were stimulated after the vibratory perception threshold was determined for each tooth. Suprathreshold stimulation was repeated thrice per session, in a total of three sessions performed on three consecutive days. Statistical inference on cluster level identified increased blood-oxygen-level-dependent signal during vibratory dental stimulation, primarily in the insular cortex bilaterally and in the supplementary motor cortex. No significant brain activation was observed in the somatosensory cortex with this stimulation protocol. These results agree with previous findings obtained from invasive direct electrical cortical stimulation of the human insula.

Adult↗