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Location-probability profiles for the mouth region of human primary motor-sensory cortex: model and validation.

The mouth representation of the human, primary motor cortex (M1) is not reliably identified by surface anatomy but may be reliably localized by means of spatial coordinates. For this report, three quantitative metanalyses were performed which jointly described the mean location, location variability and location-probability profiles of the human M1-mouth representation. First, a literature metanalysis of intersubject functional-area variability was performed using eleven, per-subject studies, each of which reported a coordinate-referenced measure of intersubject variability for one or more brain areas. From these data, a weighted-mean value for intersubject variability was computed, which proved to be small (5.6 mm, standard deviation), consistent across coordinate axes (x, y, z), and consistent across brain areas. Second, a literature metanalysis of the location of M1-mouth was performed using seven, coordinate-referenced, group-mean studies (71 subjects in all), each of which reported a grand-average location for M1-mouth. From this, a weighted-mean location and weighted values for total variability (interlaboratory plus interindividual) were determined. Using these two literature metanalyses as input data, location-probability profiles were computed for the cardinal axes (x, y, and z) of the reference space, using the functional volumes modeling (FVM) statistical model. Third, an original-data metanalysis was performed on in-house PET data from 30 normal subjects performing overt-speech tasks. M1-mouth's mean location, location variability, and location-probability profiles were consistent with those conjointly modeled by FVM from the two literature metanalyses. Collectively, these observations provide a detailed, consensus probabilistic description of the location of the human M1-mouth representation in standardized coordinates.

Adult↗

Variability of cerebral hemoglobin concentration in very preterm infants during the first 6 hours of life.

Cerebral hemoglobin concentration (cHbc), a major determinant of oxygen transport capacity in the brain, shows a considerable variability due to physiological and methodological factors. In order to determine the (relative) contribution of these factors, the cHbc variability within the first 6 hours of life was studied in 28 very preterm infants using near infrared spectrophotometry (NIRS). Mean cHbc values were 46.4 +/- 14.1 micromol/l (2.75 +/- 0.84 ml/100 g). Is the variability in cHbc related to the methodology of cHbc measurements or to physiological variables? A statistical model of stepwise regression (backward selection) with 13 independent variables and with cHbc as a dependent variable showed that, from the total variability of +/- 14.1 micromol/l, only 3.7 micromol/l (26%) were of methodological origin, while the major portion, 9.3 micromol/l (66%) were related to four physiological variables: birth weight, gestational age, blood glucose and transcutaneous carbon dioxide tension. The remaining 1.1 micromol/l (7.8%) were unexplained. We conclude that NIRS, which allows continuous monitoring of cerebral oxygenation and metabolism even in the first hours of postnatal life, is a valid technique to measure cHbc in very preterm infants. The major portion of the large variability of early cHbc registrations can be attributed to physiological factors.

Age Factors↗

Measurement error and dietary intake.

This chapter reviews work of Carroll, Freedman, Kipnis, and Li (1998) on the statistical analysis of the relationship between dietary intake and health outcomes. In the area of nutritional epidemiology, there is some evidence from biomarker studies that the usual statistical model for dietary measurements may break down due to two causes: (a) systematic biases depending on a person's body mass index; and (b) an additional random component of bias, so that the error structure is the same as a one-way random effects model. We investigate this problem, in the context of (1) the estimation of the distribution of usual nutrient intake; (2) estimating the correlation between a nutrient instrument and usual nutrient intake; and (3) estimating the true relative risk from an estimated relative risk using the error-prone covariate. While systematic bias due to body mass index appears to have little effect, the additional random effect in the variance structure is shown to have a potentially important impact on overall results, both on corrections for relative risk estimates and in estimating the distribution usual of nutrient intake. Our results point to a need for new experiments aimed at estimation of a crucial parameter.

Bias↗

A unified statistical and information theoretic framework for multi-modal image registration.

We formulate and interpret several registration methods in the context of a unified statistical and information theoretic framework. A unified interpretation clarifies the implicit assumptions of each method yielding a better understanding of their relative strengths and weaknesses. Additionally, we discuss a generative statistical model from which we derive a novel analysis tool, the auto-information function, as a means of assessing and exploiting the common spatial dependencies inherent in multi-modal imagery. We analytically derive useful properties of the auto-information as well as verify them empirically on multi-modal imagery. Among the useful aspects of the auto-information function is that it can be computed from imaging modalities independently and it allows one to decompose the search space of registration problems.

Algorithms↗

The spectral dynamics and its applications in EEG.

The method of spectral dynamics is introduced to process slow changes in EEG. This method is based on evaluation of distance between EEG spectra. The typical application field is pharmaco-EEG after single dose drug administration, where distances between pre and post drug EEG spectra are computed. The distance between two spectra may be, however, defined in several different ways. The paper deals with the well known Lp metrics and with the metrics alpha that plays an important role in discriminating stationary processes with different spectra. The Lp and alpha metrics are non-equivalent and their properties, consistency and robustness, are studied in a simple statistical model.

Animals↗

The occurrence of fibre-type grouping in healthy human muscle: a quantitative study of cross-sections of whole vastus lateralis from men between 15 and 83 years.

Methods that objectively assess the muscle fibre-type arrangement may improve the detection of fibre-type grouping, a diagnostic sign of a denervation and reinnervation process. To distinguish between a diseased and a normal muscle, there is a need for quantitative data on the fibre-type arrangement in healthy human muscles at different ages. In this study, cross-sections were prepared of whole autopsied vastus lateralis muscle from 24 previously physically healthy men, aged 15 to 83 years. The arrangements of type 1 and type 2 fibers were assessed in terms of the number of enclosed fibres in individual fascicles throughout each muscle. Recent improvements to the enclosed fibre method were used to define measures of randomness which facilitated the combination of several sample areas and the quantification of the fibre-type arrangements. Segregation was typical for young muscles, randomness was most common between 30 and 50 years of age, while some fibre-type grouping was considered "normal" in old muscles. The arrangements of type 1 and type 2 fibres were quantitatively similar, irrespective of the age of the individual. The results imply that the fibre population changes considerably during a lifetime, and that it undergoes a continuous denervation and reinnervation process with normal ageing. Because of its importance, age should be accommodated in the analysis of a muscle sample, irrespective of the statistical model and method used.

Adolescent↗

Multivariate approach to differential diagnosis of acute meningitis.

A previously reported statistical model based on a combination of four parameters (total polymorphonuclear cell count in cerebrospinal fluid (CSF), CSF/blood glucose ratio, age and month of onset) appeared effective in differentiating acute viral meningitis (AVM) from acute bacterial meningitis (ABM). The objectives of this study were to validate this model on a large independent sample of patients with acute meningitis and to build and validate a new model based on this sample. Of 500 consecutive cases of community-acquired meningitis reviewed retrospectively, 115 were ABM, 283 were AVM and 102 were of uncertain etiology. For each of the ABM and AVM cases, the probability of ABM versus AVM (pABM) was calculated for both models. Sensitivity, specificity and predictive values as well as areas under the receiver operating characteristic (ROC) curves were calculated for both models. The original model proved an accurate and reliable diagnostic test. Its area under the ROC curve was 0.981. For pABM = 0.1, its negative and positive predictive values were 0.99 and 0.68, respectively. The new model retained four slightly different independent variables: CSF protein level, total CSF polymorphonuclear cell count, blood glucose level and leukocyte count. Its area under the ROC curve was 0.991 and, for pABM = 0.1, its negative and positive predictive values were 0.99 and 0.85, respectively. In conclusion, both models provide a valuable aid in differentiating AVM from ABM. They should be further evaluated in a prospective appraisal of their contribution to therapeutic decision making.

Acute Disease↗

Sampling rate and the estimation of ensemble variability for repetitive signals.

The measurement of ensemble variability in time-aligned event signals is studied in relation to sampling rate requirements. The theoretical analysis is based on statistical modelling of time misalignment in which the time resolution is limited by the length of the sampling interval. For different signal-to-noise ratios (SNRs), the sampling rate is derived which limits the misalignment effect to less than 10% of the noise effect. Each signal is assumed to be corrupted by additive noise. Using a normal QRS complex with a high SNR (approximately equal to 30 dB), a sampling rate of approximately 3 kHz is needed for accurate ensemble variability measurements. This result is surprising since it implies that the Nyquist rate is far too low for accurate variability measurements. The theoretical results are supplemented with results obtained from an ECG database of 94 subjects for which the ensemble variability is computed at different sampling rates using signal interpolation. The ensemble variability is substantially reduced (40%) when increasing the rate from 1 to 3 kHz, thus corroborating the results suggested by the theoretical analysis.

Electrocardiography↗

Heritability and factors affecting growth traits and age at first calving of zebu beef heifers in south-eastern Mexico.

Information for this study was obtained from a commercial beef enterprise located in the subhumid tropics of Yucatan, Mexico. Data from 664 females of different zebu breeds born from 1972 to 1983 were considered for analyses. Weaning and 18-month weights were adjusted to 240 (W240) and to 550 (W550) days of age, respectively. The statistical model included the fixed effects of years of birth, season of birth, age of dam at calving, breed of heifer and the random effect of sire within breed. Arithmetic mean +/- standard deviations were 32.1 +/- 3.6 kg, 208.3 +/- 29.1 kg, 678.1 +/- 94.6 g, 308.7 +/- 29.7 kg, 342.3 +/- 89.8 g and 1,060.2 +/- 118.7 days for birth weight (BW), W240, average preweaning daily gain (ADG), W550 postweaning daily gain (PDG) and age at first calving (AFC), respectively. Year and season of birth had significant (P < 0.05) effects on W240, ADG, W550, PDG and AFC. Parity number was significant (P < 0.05) for BW, W240, ADG and AFC. Breed differences were significant (P < 0.01) for all traits, except BW. Guzerat heifers were heavier at weaning and W550 than heifers from the other breeds. Guzerat heifers first calved at an average age of 995 days; Brahman and commercial zebu heifers calved about 50 to 60 days later and the Indubrazil and Gyr heifers about 2 months later still. The heritability estimates were 0.24 +/- 0.13 for BW, 0.26 +/- 0.14 for W240, 0.29 +/- 0.14 for ADG, 0.43 +/- 0.17 for W550, 0.56 +/- 0.20 for PDG and 0.46 +/- 0.15 for AFC.

Aging↗

Transthoracic echocardiography does not improve prediction of outcome over APACHE II in medical-surgical intensive care.

PURPOSE: To examine the hypothesis that transthoracic echocardiographic findings predict mortality in critically ill patients. METHODS: A retrospective analysis of concurrently collected data for consecutive patients from May 1996 to May 1998 who had transthoracic echocardiography on or within six months of admission to the medical surgical intensive care (MSICU). We examined the role of physiologic, clinical, and echocardiography variables in predicting the mortality of patients admitted to the MSICU. Three logistic regression models were developed: 1) clinical; 2) echocardiographic; and 3) combined clinical with echocardiographic. Univariate and multivariate analyses were performed and the relative strength of clinical and echocardiographic predictors was compared using odds ratio (OR) and receiver-operator-characteristic (ROC). RESULTS: Of 4,070 MSICU patient admissions, 1,093 patients had transthoracic echocardiography; the study group comprised 942 patients with complete clinical and echocardiographic data. The MSICU mortality was 28%. For the combined model, analyses identified left ventricular systolic function (LVSF), [OR 1.26; confidence interval (CI) 1.01-1.57], severe tricuspid regurgitation (TR) (OR 3.72; CI 1.04-13.24), medical diagnosis (OR 1.91; CI 1.15-3.19), and acute physiology and chronic health evaluation (APACHE) II score (OR 1.27; CI 1.23-1.31), as predictors of MSICU mortality. The combined model yielded an area under ROC curve of 0.913. For the clinical model, analyses identified age (OR 1.04; CI 1.02-1.05) and APACHE II (OR 1.32; 1.26-1.35) as predictors of mortality with an area under ROC curve of 0.917. For the echocardiography model, TR (OR 2.40; 1.08-5.38), severe aortic insufficiency (AI) (OR 4.13; CI 1.17-16.29) and pulmonary hypertension (OR 2.05; 1.01-4.09) were identified as predictors of outcome with an ROC curve of 0.536 for this model. CONCLUSION: Statistical models utilizing clinical variables are predictive of mortality in MSICU. Models that include diagnostic transthoracic echocardiography variables do not provide incremental value to predict ICU mortality. These findings may have implications for non-invasive hemodynamic assessment of critically ill patients, and raise the hypothesis that echocardiography-guided interventions may not alter outcome in ICU.

APACHE↗

Welfare reform and interstate migration of poor families.

The thesis of this study is that as a result of increased inequalities in welfare rules, the 1996 welfare reform act not only enhanced incentives for poor families to move but also (and perhaps more important) created disincentives for them to stay in "race to the bottom" states. In testing this thesis, we evaluated the mediating and moderating roles of state economic development and family structure. We merged data from three main sources: the 1996-1999 panel of the Survey of Income and Program Participation, the Urban Institute's Welfare Rules Database, and state economic data from the Bureau of Labor Statistics. Modeling both destination (pull) and departure (push) effects of welfare policy measures and selected covariates in a nested discrete-time event-history migration analysis, we found robust support for the thesis that stringency in state welfare-eligibility and behavior-related rules stimulated interstate out-migration of poor families in the United States. However poor families were not drawn to states with relatively more-lenient welfare rules, although stringency in state welfare dollar benefits inhibited in-migration and state unemployment patterns may have conditioned the migration effects of welfare-reform rules on the choice of destination. Single mothers were not more directly affected by welfare-eligibility and behavior-related rules than were poor married couples.

Data Collection↗

[Medical registries. Benefits and limitations].

Traditionally, registers are understood as tools of epidemiological research. Recently, medical registers have encountered new tasks in quality management and research on medical care. When registers are complete and representative for a target population, they complement the epidemiological and clinical studies that usually focus on specific endpoints using selected study populations. In this process, registers can benefit substantially from the established methodology of planned studies, for instance by application of survey sampling techniques. In order to fulfil the steadily rising expectations, registers have to meet increased methodological standards. Organization and data management should be orientated towards the standards that are meanwhile generally accepted for randomized controlled trials. The evaluation has to go beyond simple descriptive statistics towards complex statistical model building in order to cope with the unavoidable problem of internal validity of comparisons within registers. If registers fulfil these requirements, they are valuable sources of information (that cannot be replaced by other tools) on the spread of risk factors and diseases and on the distribution and usefulness of preventive measures and therapies; general proof of their efficacy should be provided by randomized clinical trials.

Biomedical Research↗

Prefrontal-basal ganglia pathways are involved in the learning of arbitrary visuomotor associations: a PET study.

Primates can learn to associate sensory cues with particular movements according to arbitrary rules. We used positron emission tomography (PET) to study the neural network involved in learning such arbitrary associations by trial and error. Ten subjects were scanned at four different stages of learning a visuomotor conditional task (VC). The subjects were required to associate four different visual patterns, presented one at a time, with four different finger movements. Scan 1 was acquired during initial learning. Scans 2, 3 and 4 were performed after further interscan training periods of 1, 3 and 5 min. In order to control for non-specific time effects that could have confounded the learning-related rCBF changes, we also acquired four sensory-matched control scans, in which no movements were performed. In order to evaluate changes over time that were specific to learning the association of visual cues with movements, we acquired four scans during the learning of a motor sequence task. The statistical model tested with SPM considered both main effects of tasks and task x time interactions independently for each of the three experimental conditions. The right lingual gyrus and the left parahippocampal cortex increased their activity over scans in the VC task as compared to the sensory control. The right inferior frontal sulcus, the body of the caudate nucleus and a left cingulate motor area were specifically implicated in learning the VC task, showing task x time interactions with the motor sequence task. These findings suggest that the learning process involves a distributed network in the ventral extrastriate and prefrontal cortex, in association with the basal ganglia and the parahippocampal gyrus.

Adult↗

Exponential mapping of quantitative trait loci governing allometric relationships in organisms.

Allometric scaling relationships or quarter-power rules, as a universal biological law, can be viewed as having some genetic component, and the particular genes (or quantitative trait loci, QTL) underlying these allometric relationships can be mapped using molecular markers. We develop a mathematical and statistical model for mapping allometric QTL on the basis of nonlinear power functions using Taylor's approximation theory. Simulation studies indicate that the QTL position and effect can be estimated using our model, but the estimation precision can be improved from the higher- over lower-order approximation when the sample size used and gene effects are small. The application of our approach in a real example from forest trees leads to successful detection of a QTL governing the allometric relationship between 3rd-year stem height and 3rd-year stem biomass. It is expected that our model will have broad implications for genetic, evolutionary, biomedical and breeding research.

Algorithms↗

Minimum sample sizes for identifying chromosomal fragile sites from individuals: Monte Carlo estimation.

A Monte Carlo simulation procedure was used to estimate the exact level of the standardized X2 test statistic (Xs2) for randomness in the FSM methodology for the identification of fragile sites from chromosomal breakage data for single individuals. A random-number generator was used to simulate 10,000 chromosomal breakage data sets, each corresponding to the null hypothesis of no fragile sites for numbers of chromosomal breaks (n) from 1 to 2000 and at three levels of chromosomal band resolution (k). The reliability of the test was assessed by comparisons of the empirical and nominal alpha levels for each of the corresponding values of n and k. These analyses indicate that the sparse and discrete nature of chromosomal breakage data results in large and unpredictable discrepancies between the empirical and nominal alpha levels when fragile site identifications are based on small numbers of breaks (n < 0.5 k). With n > or = 0.5 k, the distribution of Xs2 appears to be stable and non-significant differences in the empirical and nominal alpha levels are generally obtained. These results are inherent to the nature of the data and are, therefore, relevant to any statistical model for the identification of fragile sites from chromosomal breakage data. For FSM identification of fragile sites at alpha = 0.05, we suggest that n > or = 0.5 k is the minimum reliable number of mapped chromosomal breaks per individual.

Chromosome Fragile Sites↗

Respiratory heat loss of Holstein cows in a tropical environment.

In order to develop statistical models to predict respiratory heat loss in dairy cattle using simple physiological and environmental measurements, 15 Holstein cows were observed under field conditions in a tropical environment, in which the air temperature reached up to 40 degrees C. The measurements of latent and sensible heat loss from the respiratory tract of the animals were made by using a respiratory mask. The results showed that under air temperatures between 10 and 35 degrees C sensible heat loss by convection decreased from 8.24 to 1.09 W m(-2), while the latent heat loss by evaporation increased from 1.03 to 56.51 W m(-2). The evaporation increased together with the air temperature in almost a linear fashion until 20 degrees C, but it became increasingly high as the air temperature rose above 25 degrees C. Convection was a mechanism of minor importance for respiratory heat transfer. In contrast, respiratory evaporation was an effective means of thermoregulation for Holsteins in a hot environment. Mathematical models were developed to predict both the sensible and latent heat loss from the respiratory tract in Holstein cows under field conditions, based on measurements of the ambient temperature, and other models were developed to predict respiration rate, tidal volume, mass flow rate and expired air temperature as functions of the ambient temperature and other variables.

Animals↗

Intracerebral microdialysis and intracranial compliance monitoring of patients with traumatic brain injury.

OBJECTIVE: The aims of this study were to get an impression of the relationships between intracranial compliance (IC) and Lactate/Pyruvate (L/P) ratio and temperature and L/P ratio, and to determine if patients with low IC had an increased vulnerability for the secondary insult hyperthermia (as reflected in the L/P ratio). The effects of coma treatment on the results were also studied. METHODS: Ten TBI patients were monitored for IC, in vivo microdialysis (MD) and bladder temperature. Mean Glasgow Coma Scale (GCS) score was 7 (range 4-10). Three patients underwent induced coma treatment. Three statistical models were used to look at the relationships between IC, temperature and L/P ratio in patients with and without coma. RESULTS: We found that with high temperature L/P ratios increased as IC decreased (P < 0.0001). The patients with coma treatment had significantly higher average L/P ratios (P < 0.02). The effect of IC on the L/P ratio differed by coma treatment (P < 0.02). The temperature effect was not dependent on coma treatment (P < 0.49). CONCLUSIONS: These findings suggest the importance of avoiding hyperthermia in TBI patients, especially in patients with low or decreased IC (monitored or anticipated). The present technical solution seems promising for analysis of complex clinical data.

Adult↗

Conditioning on certain random events associated with statistical variability in PK/PD.

In PK/PD data analysis, statistical models involving random variables are developed. At times an analysis can be carried out by conditioning on certain random events involving these variables. This paper attempts to clarify issues regarding conditioning. In particular, conditioning is examined as it relates to a number of disparate practical matters: missing covariate values, dose titration, BQL data, "no change from baseline" data, and the use of a truncated intraindividual probability distribution for PK observations.

Algorithms↗