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PubMed2002

Statistical evaluation of the revised fixed-dose procedure.

The fixed-dose procedure (FDP) was introduced as OECD Test Guideline 420 in 1992, as an alternative to the conventional median lethal dose (LD50) test for the assessment of acute oral toxicity (OECD Test Guideline 401). The FDP uses fewer animals and causes less suffering than the conventional test, while providing information on the acute toxicity to allow substances to be ranked according to the EU hazard classification system. Recently the FDP has been revised, with the aim of providing further reductions and refinements, and classification according to the criteria of the Globally Harmonized Hazard Classification and Labelling scheme (GHS). This paper describes the revised FDP and analyses its properties, as determined by a statistical modelling approach. The analysis shows that the revised FDP classifies substances for acute oral toxicity generally in the same, or a more stringent, hazard class as that based on the LD50 value, according to either the GHS or the EU classification scheme. The likelihood of achieving the same classification is greatest for substances with a steep dose-response curve and median toxic dose (TD50) close to the LD50. The revised FDP usually requires five or six animals with two or fewer dying as a result of treatment in most cases.

Algorithms↗

PubMed2005

Towards joint disease mapping.

This article discusses and extends statistical models to jointly analyse the spatial variation of rates of several diseases with common risk factors. We start with a review of methods for separate analyses of diseases, then move to ecological regression approaches, where the rates from one of the diseases enter as surrogate covariates for exposure. Finally, we propose a general framework for jointly modelling the variation of two or more diseases, some of which share latent spatial fields, but with possibly different risk gradients. In our application, we consider mortality data on oral, oesophagus, larynx and lung cancers for males in Germany, which all share smoking as a common risk factor. Furthermore, the first three cancers are also known to be related to excessive alcohol consumption. An empirical comparison of the different models based on a formal model criterion as well as on the posterior precision of the relative risk estimates strongly suggests that the joint modelling approach is a useful and valuable extension over individual analyses.

Epidemiologic Studies↗

PubMed2004

Retention of basic science knowledge: a comparison between body system-based and clinical presentation curricula.

BACKGROUND: When the University of Calgary implemented the clinical presentation (CP) curriculum in 1994, it was prospectively decided to administer the National Board of Medical Examiner's Comprehensive Basic Science Exam (CBSE) as a measure of students' basic science knowledge retention. PURPOSE: The exam performance from 2 classes (1995, 1996) of the previous system-based (SB) curriculum was compared to exam performance of 2 classes (2000, 2002) of the CP curriculum. METHODS: Data analyses employed 2 statistical models (covariate multiple linear regression and hierarchical mixed effects), and effect sizes were computed. RESULTS: Differences between CBSE mean scores produced by students from the SB and CP curricula showed a curricular effect on students' retention of basic science knowledge. However, preexisting differences between groups were found to be in the small-to-medium range. CONCLUSION: Evidence supporting the potential of schemes within a CP curriculum and their relation to basic science knowledge retention was observed. Effect size for the CP curriculum on students' retention of basic science knowledge was substantial; however, a notable part of that difference can be accounted for by extraneous and confounding factors. Further research utilizing more rigorous designs to investigate the relation between schemes and basic science retention is warranted.

Alberta↗

PubMed1992

Women's social roles and their exercise participation.

How women's social roles such as parenthood, marital status and employment status affect their exercise participation, is important for the rational planning of suitable and effective exercise programs for women in different social contexts. A secondary analysis of a large data-base of urban women aged 20-49 (n = 5939) was carried out to determine if social roles, their characteristics and their combinations were related to women's exercise participation. Parenthood and marital status were significantly related to whether women exercise, and among those exercising, all three roles were significantly related to the amount of exercise. Statistical modelling, including all three roles and their interactions, controlling for age and education, showed that with respect to whether women exercise, parenthood affected exercise participation most and that its effect was dependent on age. Of the role characteristics only the number of children and overall satisfaction with daily activities improved the prediction of exercising. With respect to how much women exercise, the effect of parenthood interacted with marital status. Married parents were least likely to exercise very much. Of the role characteristics only overall satisfaction with daily activities improved the prediction of the amount of exercise.

Activities of Daily Living↗

PubMed1991

Predictors of the accuracy of telephoned dietary recall data in a group of free-living elderly subjects.

As part of a study evaluating the accuracy of dietary intake data from telephoned 24-hour dietary recalls, an attempt was made to predict, on the basis of their health, social, demographic and dietary characteristics, which subjects would provide data containing the greatest error. Unexpectedly, the statistical model for the overall error score was predictive of smaller rather than larger errors. All variables it contained were reasons why an individual might have a heightened awareness of their food consumption. Work should be undertaken to determine whether this model also has predictive ability in face-to-face dietary interview settings and with non-elderly subjects.

Aged↗

PubMed2001

Conditional local influence in case-weights linear regression.

The local influence approach proposed by Cook (1986) makes use of the normal curvature and the direction achieving the maximum curvature to assess the local influence of minor perturbation of statistical models. When the approach is applied to the linear regression model, the result provides information concerning the data structure different from that contributed by Cook's distance. One of the main advantages of the local influence approach is its ability to handle the simultaneous effect of several cases, namely, the ability to address the problem of 'masking'. However, Lawrance (1995) points out that there are two notions of 'masking' effects, the joint influence and the conditional influence, which are distinct in nature. The normal curvature and the direction of maximum curvature are capable of addressing effects under the category of joint influences but not conditional influences. We construct a new measure to define and detect conditional local influences and use the linear regression model for illustration. Several reported data sets are used to demonstrate that new information can be revealed by this proposed measure.

Humans↗

PubMed2005

Growth patterns at distal radius and tibial shaft in pubertal girls: a 2-year longitudinal study.

UNLABELLED: Bone changes, in terms of both size and BMD, were assessed longitudinally in pubertal girls. Before puberty, BMD at the distal radius declined, whereas bone size increased, suggesting that normal growing girls experience a transient period of increased bone fragility. This could explain the elevated low-trauma forearm fracture rates reported in earlier studies. INTRODUCTION: Longitudinal data on bone growth during puberty are sparse. Such information is needed to understand the sequence of biological changes, the physical and mechanical consequences for the growing skeleton, and the implications for later life. MATERIALS AND METHODS: The geometric properties and volumetric BMD (vBMD) of the distal radius and tibial shaft were measured using pQCT in 258 pubertal girls followed over 2 years. A new hierarchical linear statistical modeling approach was used to determine true longitudinal trends. RESULTS: The growth rates of cross-sectional area (CSA) and BMC of the distal radius peaked at 16 and 9 months before menarche, respectively. This growth asynchrony between bone size and mass meant that total vBMD of the distal radius declined until 1 year before menarche. At the tibial shaft, total vBMD and cortical vBMD increased monotonically without any such transient reduction. Cortical thickness increased linearly, which was accounted for mainly by bone formation at the periosteal surface before menarche, but by both periosteal and endocortical apposition after menarche. During puberty, the ratio of cortical-to-total CSA of the tibial shaft increased and that of marrow-to-total CSA decreased. CONCLUSIONS: The temporal pattern of bone growth during puberty differs at the distal radius and tibial shaft. A transient decrease in vBMD, arising from asynchronous bone size and mass growth, occurs only at the radius. In the tibia, the mechanism of cortical thickening changes from periosteal apposition premenarche to both periosteal and endocortical apposition postmenarche.

Adolescent↗

PubMed2005

Statistical approach for detection and localization of a fluorescing mouse tumor in Intralipid.

We present a method for detecting and localizing a fluorescing tumor obscured underneath several millimeters of a multiply scattering, homogeneous medium from fluorescence measurements made above the surface. Using a statistical model of the measurement system, we develop approaches for detection by use of a binary hypothesis testing approach and localization by use of maximum-likelihood estimation. We also compute the probability of tumor detection and the Cramér-Rao lower bound for the localization estimate error, which are performance metrics that could potentially be optimized in an experimental design. We validate the methods in an experimental study involving an excised mouse tumor tagged with a new folate-indocyanine dye and obscured under a tissue-simulating lipid suspension.

Algorithms↗

PubMed2004

Use of a dense single nucleotide polymorphism map for in silico mapping in the mouse.

Rapid expansion of available data, both phenotypic and genotypic, for multiple strains of mice has enabled the development of new methods to interrogate the mouse genome for functional genetic perturbations. In silico mapping provides an expedient way to associate the natural diversity of phenotypic traits with ancestrally inherited polymorphisms for the purpose of dissecting genetic traits. In mouse, the current single nucleotide polymorphism (SNP) data have lacked the density across the genome and coverage of enough strains to properly achieve this goal. To remedy this, 470,407 allele calls were produced for 10,990 evenly spaced SNP loci across 48 inbred mouse strains. Use of the SNP set with statistical models that considered unique patterns within blocks of three SNPs as an inferred haplotype could successfully map known single gene traits and a cloned quantitative trait gene. Application of this method to high-density lipoprotein and gallstone phenotypes reproduced previously characterized quantitative trait loci (QTL). The inferred haplotype data also facilitates the refinement of QTL regions such that candidate genes can be more easily identified and characterized as shown for adenylate cyclase 7.

Adenylyl Cyclases↗

PubMed2006

Calculating uncertainty of measurement for serology assays by use of precision and bias.

BACKGROUND: In many countries, regulatory authorities that use International Organization for Standardization Standards to assess laboratory competence require an estimate of the uncertainty of measurement (MU) of assay test results. This estimate can be determined by identifying all sources of variation, calculating the extent of variation, and using established methods to combine the uncertainty. Alternatively, laboratory staff may use existing data generated from evaluations, proficiency testing, or external run controls to determine MU. METHODS: A quality-control (QC) sample with low reactivity was tested by laboratories participating in a national QC program. The results of testing the QC sample were entered into a shared database by use of an Internet-based program, EDCNet. Using a statistical approach that accounts for imprecision and bias of test results, we estimated the MU of the laboratories. RESULTS: A total of 2167 test results of a single QC sample reported by 18 laboratories were analyzed, and the MU of 1 laboratory was estimated by the statistical model described. CONCLUSION: Using peer-group run control data, MU of serologic testing can be estimated by taking into account both imprecision and bias.

Algorithms↗

PubMed1990

Cardiac arrhythmias and left ventricular function in respiratory failure from chronic obstructive pulmonary disease.

In 22 patients with COPD, we studied the relationship between left ventricular function and cardiac arrhythmias. Ventricular arrhythmias were detected on a 24-h ECG recorded at the beginning of the observation period and after a stable improvement of RF. Left ventricular function was evaluated by equilibrium-gated radionuclide angiocardiography measuring LVEF, PER and PFR. We found a significant decrease in the arrhythmia score after improvement of RF; LVEF and PFR were slightly depressed in six and nine patients, respectively. A "step-up" multiple regression analysis revealed a significant inverse correlation between PFR and ventricular arrhythmias during worsened RF, whereas LVEF, arterial blood gases and clinical data were not significantly predictive variables. Thus, a depressed left ventricular diastolic performance seems to be a predictive factor for arrhythmias during RF from COPD. The poor definition of the statistical model suggests that other presently unknown factors contribute to the genesis of ventricular arrhythmias.

Arrhythmias, Cardiac↗

PubMed2000

Stature, age, and gender effects on reach motion postures.

The rapid adoption of software to simulate human reach motions in the design of vehicle interiors and manufacturing and office workstations has required a sophisticated understanding of human motions. This paper describes how more than 3,000 right-arm reaching motions of a diverse group of participants were captured and statistically modeled. The results demonstrate that stature and age have a larger effect than does gender on reach motion postures for motions chosen by the participants while reaching to targets placed throughout a typical automobile interior. We propose that these methods, models, and results can assist the further development of human motion simulation software for ergonomic purposes, such as for the design or evaluation of vehicle interiors or industrial workplaces, to ensure that various population groups are physically accommodated.

Adolescent↗

PubMed2006

Influence of response variability on the coding performance of central gustatory neurons.

We explored how variability in responding to taste stimuli could impact the signaling of taste quality information by neuron types and individual cells in the nucleus of the solitary tract. One hundred sixty-two neurons recorded from anesthetized rats were grouped using multivariate analysis of taste responses to the following (in m): 0.5 sucrose, 0.1 NaCl, 0.01 HCl, and 0.01 quinine-HCl. Neurons fell into one of three groups corresponding to cell types that responded optimally to sucrose, NaCl, or HCl. A statistical model was used to examine whether responses observed among neurons within each group could be correctly attributed to the optimal stimulus or another tastant on the basis of spike count. Results revealed poor classification performance in some cases attributable to wide variations in the sensitivities of neurons that compose a cell type. This outcome leads us to question whether neuron types could faithfully encode a single taste quality. We then theoretically explored whether a hypothetical observer of individual neurons could discriminate between spiking rates to different tastants during the first second of stimulus processing. Spike rate was found to be an unreliable predictor of stimulus quality for each neuron tested. However, additional analyses suggested that taste stimuli could be identified by a reader that attends to the relative spiking activities of different kinds of neurons in parallel. Rather than assigning meaning to individual neurons or categories of them, central gustatory circuits may signal quality information using a strategy that involves the relative activities of neurons with different sensitivities to tastants.

Action Potentials↗

PubMed2005

Cortical sites critical for speech discrimination in normal and impaired listeners.

We used statistical modeling to investigate variability in the cortical auditory representations of 24 normal-hearing epilepsy patients undergoing electrocortical stimulation mapping (ESM). Patients were identified as normal or impaired listeners based on recognition accuracy for acoustically filtered words used to simulate everyday listening conditions. The experimental ESM task was a binary (same-different) auditory syllable discrimination paradigm that both listener groups performed accurately at baseline. Template mixture modeling of speech discrimination deficits during ESM showed larger and more variable cortical distributions for impaired listeners than normal listeners, despite comparable behavioral performances. These results demonstrate that individual differences in speech recognition abilities are reflected in the underlying cortical representations.

Adolescent↗

PubMed2000

Mortality in male alcoholics after ten to fourteen years.

OBJECTIVE: Alcoholics frequently die prematurely. The purpose of this study was to determine: (1) whether subjects in a sample of 360 male alcoholics, followed over a period of 10-14 years, died prematurely: (2) if so, from what causes; and (3) whether such deaths are predictable from characteristics present at initial assessment. METHOD: Subjects were male veterans (N = 360) with a diagnosis of alcoholism admitted to an inpatient substance abuse treatment program at the Kansas City Veterans Affairs (VA) Medical Center during 1980-1984 who consented to participate in intake evaluations and subsequent follow-ups at 1 year and 10-14 years later. Of the 357 (99.2%) men located at the 10-14 year follow-up, 96 (26.6%) were confirmed as deceased, 255 survivors agreed to be reassessed and 6 subjects refused reassessment. Information regarding cause of death was obtained from death certificates, VA records and other sources. RESULTS: At intake, the subsequently deceased men were older, had less education, lower psychosocial functioning, more medical problems and greater psychiatric severity. Their overall death rate was 2.5 times greater than that of a reference group of men. Men in the 35-44 year age group were 5.5 times as likely to die. A statistical model utilizing measures of alcohol dependence to predict mortality from intake to 10-14 year follow-up indicated that alcoholics who limited drinking were half as likely to die whereas those who engaged in morning drinking were 2.5 times more likely to die. CONCLUSIONS: Alcoholic men, especially those in the group aged 35 to 44 years, have a significantly higher risk of premature death than a reference group of men. Men who engaged in morning drinking and could not limit drinking appeared to be at higher risk of mortality 10 years later.

Adult↗

PubMed1994

Alternative analytical methods for detecting matching effects in treatment outcomes.

Project MATCH presented a unique opportunity for a team of statisticians, data analysts and content experts to come together and explore the strengths and weaknesses of the application of various statistical models to the data of the type being collected in this large trial. The following models were evaluated: multilevel models, event history models, multiple were structural equation modeling, time series models, ordinal repeated measures designs and generalized estimating equations. No one model was found to be the perfect solution and each seemed to have something to recommend it. Future research on these methods will shed light on many issues raised. It is hoped that alcohol researchers will find useful guidelines within this chapter as they plan and carry out their studies.

Alcoholism↗

PubMed1991

[Multivariate analysis on subjective symptoms in forestry workers using chain saw].

This study was conducted to evaluate the relationship between the prevalence of subjective symptoms in workers using vibrating tools and the duration of chain saw operation and to examine whether the symptoms were relevant to factors other than the usage of vibrating tools. The statistical model of multivariate analysis was adapted to analyze individual data on the subjective symptoms of 317 chain saw operators. The obtained results were as follows: 1. In analysis of covariance, age-adjusted operating year in workers with peripheral circulatory, peripheral neurological and musculoskeletal disturbances was significantly longer than that without such disturbances. For these disturbances, partial regression coefficients of operating year were significantly high in multiple regression analysis. These results show that these disturbances and age-adjusted operating year are mutually closely related. 2. Multiple regression analysis showed that the partial regression coefficients of both operating year and age were low for nine symptoms, i.e. dulling sense of touch, joint pain, headache, dizziness and/or tinnitus, profuse sweating, discomfort of stomach, palpitation and/or dyspnea, hearing disturbance and lumbago. These results suggest that such symptoms were not related to either age or chain saw operation. 3. The results of principal component analysis were visualized in three-dimensional space in order to evaluate the relationships among the symptoms. The analysis showed that peripheral circulatory and neurological disturbances appeared independently and that general symptoms such as easy fatigability, headache, forgetfulness, vertigo and/or tinnitus, easy irritability, sleep disorder, profuse sweating, discomfort of stomach, palpitation and/or dyspnea, shoulder stiffness, hearing disturbance and lumbago consisted of four independent groups. Each group has no relationship with duration of chain saw operation. This suggests other harmful factors of the groups play a role in the prevalence of the symptoms.

Age Factors↗

PubMed2004

Teenagers' use of sexual health services: perceived need, knowledge and ability to access.

INTRODUCTION: An individual teenager's use of services may depend on perceived need, on knowledge of sexual health and local services, and on ability to access. This paper presents the first UK large-scale quantitative analysis of these factors, comparing those who use services with those who do not. METHODS: 15/16-year-olds (n = 5747) were questioned about their use of sexual health services in the SHARE trial of a school sex education programme in 25 schools in Lothian and Tayside, Scotland, UK. Multilevel statistical models examined the role of different factors on service use. RESULTS: One-third of teenagers had used a service, and use was strongly related to sexual experience. In addition, some family influences and being a school leaver were associated with service use, although we found no evidence for class, ethnic or religious barriers to use. Proximity to specialist clinics was linked with greater use, while low spending money and high parental monitoring were associated with less use. Teenagers with better knowledge, who rated their school sex education as effective, who were comfortable talking about sex and who had discussed contraception with peers were more likely to have used services. Differences in use relating to sexual experience, knowledge, feeling comfortable talking about sex and talking with peers helped to explain gender differences in service uptake. CONCLUSION: There is potential to influence service use through better knowledge and confidence imparted through school sex education, and by improving the links between services and schools.

Adolescent↗