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Intermittent degradation in performance in schizophrenia.

In a series of repeated trials, schizophrenic patients often fluctuate in performance. Our data suggest that it may be useful, not just to report an increased variance relative to nonschizophrenics, but to model these fluctuations concretely as transitions between a relatively normal and an abnormal cognitive state - an intermittent degradation in performance that may be related to transient abnormalities in CNS functioning. We define 'dialipsis' as a temporary substitution of a less efficient process of task performance. This phenomenon is mentioned in the literature, but the descriptions of dialipsis are heuristic rather than based on a statistical model. We present a mixture model in which the ordinary and degraded states are described by distinct ANOVA structures, each with its own task, subject and interaction effects, with transitions between them occurring at random times. We discuss ways of detecting dialipsis and comparing the mixture model statistically with alternative models.

Analysis of Variance↗

Evaluation of a prediction model for long-term fracture risk.

UNLABELLED: The NOF cost-effectiveness model, based on clinical risk factors and femoral neck aBMD, predicted overall fracture risk in a cohort of postmenopausal women followed for up to 22 years. INTRODUCTION: To assess the ability of a statistical model to predict long-term fracture risk for a population of postmenopausal women, we compared observed fractures to those predicted by the National Osteoporosis Foundation's (NOF) cost-effectiveness model. MATERIALS AND METHODS: In this population-based study, 393 postmenopausal Rochester, MN, women had baseline measurements of femoral neck areal BMD (aBMD) and assessment of the clinical risk factors (personal fracture history, family history of osteoporotic fracture, low body weight, and smoking status) that were included in the NOF model. They were then followed prospectively for up to 22 years. Fractures were ascertained by periodic interview and review of community medical records. Standardized incidence ratios (SIRs) compared observed fractures to predicted numbers. RESULTS: During 4782 person-years of follow-up, 212 women experienced 503 fractures, two-thirds of which were caused by moderate trauma. When undiagnosed (incidentally noted) vertebral and rib fractures were excluded, there was general concordance between observed and predicted fractures of the hip (SIR, 0.78; 95% CI, 0.56-1.01), distal forearm (SIR, 1.22; 95% CI, 0.86-1.68), spine (SIR, 0.76; 95% CI, 0.50-1.11), and all other sites combined (SIR, 1.18; 95% CI, 0.97-1.42). Fracture prediction by the NOF model was about as good after 10 years as it was earlier during follow-up. CONCLUSIONS: This study validates the ability of a statistical model based on femoral neck aBMD and common clinical risk factors to predict the actual occurrence of fractures in a cohort of postmenopausal white women.

Absorptiometry, Photon↗

Theoretical calculation and prediction of brain-blood partitioning of organic solutes using MolSurf parametrization and PLS statistics.

Sixty-three structurally diverse compounds were investigated to statistically model the brain-blood partitioning of organic solutes using theoretically computed molecular descriptors and multivariate statistics. The program MolSurf was used to compute theoretical molecular descriptors related to physicochemical properties such as lipophilicity, polarity, polarizability, and hydrogen bonding. The multivariate Partial Least Squares Projections to Latent Structures (PLS) method was used to delineate the relationship between the brain-blood partitioning of organic solutes and the theoretically computed molecular descriptors. Good statistical models were derived. Properties associated with polarity and Lewis base strength had the largest impact on the blood-brain partitioning and should be kept to a minimum to promote high partitioning. The absence of atoms capable of hydrogen bonding interactions as well as high lipophilicity and the presence of polarizable surface electrons, i.e., valence electrons, were also found to promote high brain-blood partitioning. The results indicate that theoretically computed molecular MolSurf descriptors in conjunction with multivariate statistics of PLS type can be used to successfully model the brain-blood partitioning of organic solutes and hence differentiate drugs with poor partitioning from those with acceptable partitioning at an early stage of the preclinical drug-discovery process.

Blood-Brain Barrier↗

Early childhood caries and infant feeding practice.

OBJECTIVES: Early childhood caries (ECC) has been suggested as a new term to describe the presence of caries on at least one primary tooth in children under six years of age. The prevalence and severity of ECC in low socio-economic, immigrant and indigenous communities is high. The purpose of this study was to investigate the association between selected social and behavioural variables, including previous infant feeding practice, and the presence of ECC in an Australian child population. METHOD: A cross sectional sample of 3,375 four to six-year-old children from the north Brisbane region were examined in a school based setting using dmft/s indices and a self-administered questionnaire obtained information regarding social background and past infant feeding practice. The data were modelled using a forward stepwise logistic regression procedure to explore a statistical model for ECC presence. RESULTS: Significant determinants for ECC presence were ethnicity other than Caucasian (OR=1.99, CI=1.37, 2.88), language other than English (OR=1.97, CI=1.35, 2.86), single parent status (OR=1.93, CI=1.47, 2.52), sweetened bottle contents (OR=4.29, CI=2.90, 6.38), going to sleep with the bottle (OR=1.73, CI=1.49, 2.00) and sipping from the bottle during the day (OR=1.58, CI=1.35, 1.84). CONCLUSIONS: A statistical model for ECC presence and previous infant feeding practice has been constructed. This study supports the adoption of the proposed case definition of ECC.

Beverages↗

Predicting short-term survival for patients with advanced Alzheimer's disease.

OBJECTIVE: The purpose of this study was to develop a statistical model for predicting short term survival in patients with dementia of the Alzheimer type (DAT). DESIGN: A prospective cohort study. SETTING: Three 25-bed intermediate medical care units using a structured approach to patient care management including palliative care options and patients from a second, traditional long-term care setting. PARTICIPANTS: Of 104 patients with advanced DAT monitored for 34 months, 68 patients (97% white male) who had at least one fever episode were included in the model development phase. Data from 71 additional DAT patients with at least one fever episode were used to test the statistical model. MAIN OUTCOME MEASURES: Six-month survival following a fever episode. RESULTS: Older age and higher severity of DAT at the time of the fever episode, palliative care, and hospital admission for long-term care within 6 months prior to the fever were found to be positively associated with likelihood of mortality within 6 months of the fever onset. Adjusted odds ratios for each of these variables were statistically significant. The model performed well in subsequent testing on an independent sample of patients. CONCLUSION: Results provide a formula which can be used to predict likelihood of dying within 6 months following onset of a fever in DAT patients. This statistical prediction is recommended for use in combination with clinical judgment to certify DAT patients for Medicare hospice coverage.

Age Factors↗

A model for statistical forecasting of menu item demand.

Foodservice planning necessarily begins with a forecast of demand. Menu item demand forecasts are needed to make food item production decisions, work force and facility acquisition plans, and resource allocation and scheduling decisions. As these forecasts become more accurate, the tasks of adjusting original plans are minimized. Forecasting menu item demand need no longer be the tedious and inaccurate chore which is so prevalent in hospital food management systems today. In most instances, data may be easily collected as a by-product of existing activities to support accurate statistical time series predictions. Forecasts of meal tray count, based on a rather sophisticated model, multiplied by average menu item preference percentages can provide accurate predictions of demand. Once the forecasting models for tray count have been developed, simple worksheets can be prepared to facilitate manual generation of the forecasts on a continuing basis. These forecasts can then be recorded on a worksheet that reflects average patient preference percentages (of tray count), so that the product of the percentages with the tray count prediction produces menu item predictions on the same worksheet. As the patient preference percentages stabilize, data collection can be reduced to the daily recording of tray count and one-step-ahead forecase errors for each meal with a periodic gathering of patient preference percentages to update and/or verify the existing date. The author is more thoroughly investigating the cost/benefit relationship of such a system through the analysis of new empirical data. It is clear that the system offers potential for reducing costs at the diet category or total tray count levels. It is felt that these benefits transfer down to the meal item level as well as offer ways of generating more accurate predictions, with perhaps only minor (if any) labor time increments. Research in progress will delineate expected savings more explicitly. The approach requires statistical and computer expertise primarily during the development of the tray count model and patient preference percentage table. The results of this effort can be transferred to a form that is easily utilized by food management personnel manually to generate menu item demand forecasts.

Computers↗

The application of analysis of variance (ANOVA) to different experimental designs in optometry.

Analysis of variance (ANOVA) is the most efficient method available for the analysis of experimental data. Analysis of variance is a method of considerable complexity and subtlety, with many different variations, each of which applies in a particular experimental context. Hence, it is possible to apply the wrong type of ANOVA to data and, therefore, to draw an erroneous conclusion from an experiment. This article reviews the types of ANOVA most likely to arise in clinical experiments in optometry including the one-way ANOVA ('fixed' and 'random effect' models), two-way ANOVA in randomised blocks, three-way ANOVA, and factorial experimental designs (including the varieties known as 'split-plot' and 'repeated measures'). For each ANOVA, the appropriate experimental design is described, a statistical model is formulated, and the advantages and limitations of each type of design discussed. In addition, the problems of non-conformity to the statistical model and determination of the number of replications are considered.

Analysis of Variance↗

Effect of screening and adjuvant therapy on mortality from breast cancer.

BACKGROUND: We used modeling techniques to assess the relative and absolute contributions of screening mammography and adjuvant treatment to the reduction in breast-cancer mortality in the United States from 1975 to 2000. METHODS: A consortium of investigators developed seven independent statistical models of breast-cancer incidence and mortality. All seven groups used the same sources to obtain data on the use of screening mammography, adjuvant treatment, and benefits of treatment with respect to the rate of death from breast cancer. RESULTS: The proportion of the total reduction in the rate of death from breast cancer attributed to screening varied in the seven models from 28 to 65 percent (median, 46 percent), with adjuvant treatment contributing the rest. The variability across models in the absolute contribution of screening was larger than it was for treatment, reflecting the greater uncertainty associated with estimating the benefit of screening. CONCLUSIONS: Seven statistical models showed that both screening mammography and treatment have helped reduce the rate of death from breast cancer in the United States.

Adult↗

A framework for predictive modeling of anatomical deformations.

A framework for modeling and predicting anatomical deformations is presented, and tested on simulated images. Although a variety of deformations can be modeled in this framework, emphasis is placed on surgical planning, and particularly on modeling and predicting changes of anatomy between preoperative and intraoperative positions, as well as on deformations induced by tumor growth. Two methods are examined. The first is purely shape-based and utilizes the principal modes of co-variation between anatomy and deformation in order to statistically represent deformability. When a patient's anatomy is available, it is used in conjunction with the statistical model to predict the way in which the anatomy will/can deform. The second method is related, and it uses the statistical model in conjunction with a biomechanical model of anatomical deformation. It examines the principal modes of co-variation between shape and forces, with the latter driving the biomechanical model, and thus predicting deformation. Results are shown on simulated images, demonstrating that systematic deformations, such as those resulting from change in position or from tumor growth, can be estimated very well using these models. Estimation accuracy will depend on the application, and particularly on how systematic a deformation of interest is.

Biomechanical Phenomena↗

Multiple phenotype modeling in gene-mapping studies of quantitative traits: power advantages.

Genomewide searches for loci influencing complex human traits and diseases such as diabetes, hypertension, and obesity are often plagued by low power and interpretive difficulties. Attempts to remedy these difficulties have typically relied on, and have promoted the use of, novel subject-ascertainment schemes, larger sample sizes, a greater density of DNA markers, and more-sophisticated statistical modeling and analysis strategies. Many of these remedies can be costly to implement. We investigate the utility of a simple statistical model for the mapping of quantitative-trait loci that incorporates multiple phenotypic or diagnostic endpoints into a gene-mapping analysis. The approach considers finding a linear combination of multiple phenotypic values that maximizes the evidence for linkage to a locus. Our results suggest that substantial increases in the power to map loci can be obtained with the proposed technique, although the increase in power obtained is a function of the size and direction of the residual correlation among the phenotypes used in the analysis. Extensive simulation studies are described that justify these claims, for cases in which two phenotypic measures are analyzed. This approach can be easily extended to cover more-complex situations and may provide a basis for more insightful genetic-analysis paradigms.

Chromosome Mapping↗

From innervation density to tactile acuity: 1. Spatial representation.

We tested the hypothesis that the population receptive field representation (a superposition of the excitatory receptive field areas of cells responding to a tactile stimulus) provides spatial information sufficient to mediate one measure of static tactile acuity. In psychophysical tests, two-point discrimination thresholds on the hindlimbs of adult cats varied as a function of stimulus location and orientation, as they do in humans. A statistical model of the excitatory low threshold mechanoreceptive fields of spinocervical, postsynaptic dorsal column and spinothalamic tract neurons was used to simulate the population receptive field representations in this neural population of the one- and two-point stimuli used in the psychophysical experiments. The simulated and observed thresholds were highly correlated. Simulated and observed thresholds' relations to physiological and anatomical variables such as stimulus location and orientation, receptive field size and shape, map scale, and innervation density were strikingly similar. Simulated and observed threshold variations with receptive field size and map scale obeyed simple relationships predicted by the signal detection model, and were statistically indistinguishable from each other. The population receptive field representation therefore contains information sufficient for this discrimination.

Animals↗

Genotype x environment interaction for milk production in Guernsey cattle.

International genetic evaluations that use national genetic evaluation results as input need to acknowledge country boundaries. The current model for international evaluation treats each country as a genetically separate trait, i.e., assumes milk production to be similar within country, but different between countries. The use of cow performance records does not require such restriction, and allows for other statistical models to consider genotype x environment interaction. First-lactation records from 40,000 Guernsey cows in four countries (Australia, Canada, United States, and South Africa) were used to detect and describe genotype x environment interaction for milk production traits. Five statistical models were considered: single-trait across-county (ST), single-trait across-country with heterogeneous residual variance (SThet), multiple-trait across-country (MT), multiple-trait herd cluster model (HC), and reaction norm model (RR). For the herd cluster model, herds were clustered into groups based on information on herd management, genetic composition, and climate. Reaction norms describe the phenotype expressed by a genotype as a function of the environment, and was modeled by random regression on the herd average for peak milk yield as the descriptor of production environment. Gibbs sampling was used to make inferences about the parameters of interest, and models were compared based on goodness of fit and deviance information criterion. Posterior mode of the heritability for the single-trait model was 0.32, and ranged from 0.15 to 0.53 for models SThet and MT. Posterior mode of the genetic correlations between countries estimated with model MT were generally high (0.78 to 0.90). However, posterior SD were high (up to 0.15 for Australia-South Africa), and values near unity for the genetic correlations were not unlikely. Model HC gave more precise inferences but lower goodness of fit compared with model MT. Results from model RR provided evidence for heterogeneity of genetic variances. This model was least supported by the data, probably because heterogeneity of residual variances was not considered. Among the models in this study, the one with homogeneous genetic and heterogeneous residual variances across countries fitted best to the data, and we expect a model for which the assumption of homogeneous genetic variance is relaxed to show an even better fit to the data.

Animals↗

First attempts at prediction of DNA strand-break yields using nanodosimetric data.

We present the first results of our attempts to correlate yields of ionisation clusters in a gas model of DNA and corresponding double-strand break (DSB) yields in irradiated plasmids, using a simple statistical model of DNA lesion formation. Based on the same statistical model, we also provide a comparison of simulated nanodosimetric data for electrons and published DSB yields obtained with the PARTRAC code.

Algorithms↗

Prediction of follow-up living setting in patients with lower limb joint replacement.

OBJECTIVE: The living setting to which older adults are discharged from medical rehabilitation has important social and economic implications. This study was undertaken to develop statistical models to predict living setting after medical rehabilitation in persons with lower limb joint replacement. DESIGN: Information submitted from 1994 through 1998 to the Uniform Data System for Medical Rehabilitation was examined. Hip replacement was experienced by 42% of the patients, 51% experienced a knee replacement, and 7% received some combination or other lower limb procedure. RESULTS: Persons with hip replacements were slightly older than persons with knee replacements and had a longer length of stay. Logistic regression was used to develop a predictive model based on 60% of the cases. The model included five statistically significant predictor variables. CONCLUSION: Cognitive and basic motor function associated with activities of daily living, age, length of stay, and marital status were important variables in predicting if older adults would be living at home 80-180 days after rehabilitation for lower limb joint replacement.

Activities of Daily Living↗

Structural changes and fluctuations of proteins. I. A statistical thermodynamic model.

A general theory of the structural changes and fluctuations of proteins has been proposed based on statistical thermodynamic considerations at the chain level. The "structure" of protein was assumed to be characterized by the state of secondary bonds between unique pairs of specific sites on peptide chains. Every secondary bond changes between the bonded and unbonded states by thermal agitation and the "structure" is continuously fluctuating. The free energy of the "structural state" that is defined by the fraction of secondary bonds in the bonded state has been expressed by the bond energy, the cooperative interaction between bonds, the mixing entropy of bonds, and the entropy of polypeptide chains. The most probable "structural state" can be simply determined by graphical analysis and the effect of temperature or solvent composition on it is discussed. The temperature dependence of the free energy, the probability distribution of structural states and the specific heat have been calculted for two examples of structural change. The theory predicts two different types of structural changes from the ordered to disorderd state, a "structured transition" and a "gradual structural change" with rising temperature. In the "structural transition", the probability distribution has two maxima in the temperature range of transition. In the "gradual structural change", the probabilty distribution has only one maximum during the change. A considerable fraction of secondary bonds is in the unbounded state and is always fluctuating even in the ordered state at room temperature. Such structural flucutations in a single protein molecule have been discussed quantitatively. The theory is extended to include small molecules which bind to the protein molecule and affect the structural state. The changes of structural state caused by specific and non-specific binding and allosteric effects are explained in a unified manner.

Chemical Phenomena↗

Structural modeling of mixed longitudinal and cross-sectional data.

In this paper we describe some mathematical and statistical models for dealing with changes over age. We concentrate specifically on the use of a structural equation modeling (SEM) approach (using computer programs like LISREL) to deal with issues of: (1) group differences in regression parameters, (2) differences in longitudinal and cross-sectional results, (3) differences due to longitudinal attrition, and (4) mixtures of these problems. To illustrate these ideas we use data from a previous study of hypertension and intellectual abilities (from Schultz, Elias, Robbins, Streeten, and Blakeman, 1986).

Adult↗

Multiple stressor effects on benthic biodiversity of Chesapeake Bay: implications for ecological risk assessment.

In natural aquatic systems, there is frequently overlap in the spatial distribution of both natural and anthropogenic stressors, particularly at regional geographic scales. Yet the proportional risk associated with individual stressors, their cumulative effects and the manner in which they interact to affect aquatic ecology is frequently unknown, limiting the robustness of multiple-stressor ecological risk assessments (ERA). The current study used historical environmental monitoring data (1984-1999) to identify a combination of natural and anthropogenic stressors that best accounted for observed patterns of benthic biodiversity in Chesapeake Bay. Geographic information systems (GIS) were used to geographically link spatially heterogeneous databases for benthic biodiversity, water quality and sediment toxicant concentrations. Single and multiple variable regression techniques were subsequently used to develop a statistical model to explain observed patterns of benthic biodiversity. Combinations of natural stressors alone accounted for as much as 34% of the variation in benthic biodiversity, and combinations of anthropogenic toxicants accounted for as much as 48% of the variation. The consideration of both natural and anthropogenic stressors resulted in a statistical model that accounted for approximately 73% of the observed variation in benthic biodiversity of Chesapeake Bay. These results suggest that benthic biodiversity in Chesapeake Bay is a function of complex interactions among water quality characteristics and anthropogenic toxicants. Therefore, new risk assessment methodologies are required to assess the risk of multiple stressors at regional scales.

Animals↗

Population pharmacokinetics of intravenous amiodarone in patients with refractory ventricular tachycardia/fibrillation.

A population approach was used to determine the pharmacokinetics of amiodarone in 245 patients receiving intravenous amiodarone for the short-term treatment of refractory, hemodynamically destabilizing, ventricular tachycardia and/or fibrillation. A two-compartment model employing proportional statistical models to estimate intersubject variability and an additive-proportional model to estimate residual error were found to best describe the data. The mean (% coefficient of variation, CV) value for clearance was 0.22 L/hr/kg (13%), central volume of distribution was 0.30 L/kg (11%), peripheral volume of distribution was 10.0 L/kg (9.5%), and intercompartmental clearance was 0.71 L/hr/kg (16%). The mean (%CV) intersubject variance estimates were 1.52 (31%) for clearance, 0.37 (46%) for central volume, 0.37 (67%) for peripheral volume, and 0.44 (39%) for intercompartmental clearance. The estimate of residual error (%CV) was 0.53 (13%). Age, gender, height, serum creatinine concentration, serum alkaline phosphatase activity, ejection fraction, and therapeutic response to treatment did not contribute to the variability in patient pharmacokinetics. It was concluded that the pharmacokinetic parameters of amiodarone in these patients were similar to those reported for healthy volunteers and were similarly variable. Estimates of pharmacokinetic parameters made during short periods of observation may not be entirely consistent with parameters estimated during prolonged periods of observation of healthy volunteers who receive single doses.

Aged↗