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This article concerns construction of a confidence surface for tangential slopes of the dose-response surface of a combination therapy to identify where response increases as a function of drug dosage. This approach extends to the assessment of the effectiveness of the combination therapy.
The statistical properties of the EEG and the MEG are described mathematically as the result of randomly distributed dipoles. These dipoles represent the interactions of cortical neurons. For certain dipole distributions, the first- and second-order moments of the electric and magnetic fields are derived analytically. If the dipoles are in a spherical volume conductor and have no preference for any direction, the variance of a differentially measured EEG-signal is only a function of the electrode distance. In this paper, the theoretically derived variance function will be compared with EEG- and MEG-measurements. It is shown that a dipole with a fixed position and a randomly fluctuating amplitude is an adequate model for the alpha-rhythm. An expression for the covariance between the magnetic field and a differentially measured EEG-signal is derived. This covariance is considered as a function of the magnetometer position, and is compared with the measurements of Chapman et al. [23]. The theory can be used to obtain a (spatial) covariance matrix of the background noise, which occurs in evoked potential measurements. Such a covariance matrix can be used to obtain a maximum likelihood estimator of the dipole parameters in evoked potential studies, to evaluate the merits of the so-called "Laplacian derivation," and for the interpolation of electromagnetic data.
Posture control performance was quantified in three variables (swiftness, stiffness, damping). Subjects were tested with a force platform recording body sway induced by vibrators attached to the calf muscles. Parameter estimation was made with identification of a transfer function representing the stabilized inverted pendulum. It is conjectured that the state feedback parameters identified are suitable for use in assessing ability to maintain posture.
Label-free bottom-up proteomics using mass spectrometry and liquid chromatography has long been established as one of the most popular high-throughput analysis workflows for proteome characterization. However, it produces data hindered by complex and heterogeneous missing values, which imputation has long remained problematic. To cope with this, we introduce Pirat, an algorithm that harnesses this challenge using an original likelihood maximization strategy. Notably, it models the instrument limit by learning a global censoring mechanism from the data available. Moreover, it estimates the covariance matrix between enzymatic cleavage products (ie peptides or precursor ions), while offering a natural way to integrate complementary transcriptomic information when multi-omic assays are available. Our benchmarking on several datasets covering a variety of experimental designs (number of samples, acquisition mode, missingness patterns, etc.) and using a variety of metrics (differential analysis ground truth or imputation errors) shows that Pirat outperforms all pre-existing imputation methods. Beyond the interest of Pirat as an imputation tool, these results pinpoint the need for a paradigm change in proteomics imputation, as most pre-existing strategies could be boosted by incorporating similar models to account for the instrument censorship or for the correlation structures, either grounded to the analytical pipeline or arising from a multi-omic approach.
The aim of the study was to search for a multidimensional order in the psychopathology of the functional mental disorders in general. A heterogeneous group of 192 patients was investigated by means of a semistructured interview based on the Comprehensive Psychopathological Rating Scale. Principal component factor analysis revealed 5 clinically meaningful dimensions interpretable as representing dysregulation of emotion and motivation, perceptual and behavioural disintegration and dysregulation of autonomic functions.
This study was designed to determine the discriminative efficiency of the Bayley Mental and Motor Scales for classifying infants as neurologically suspicious and neurologically normal. The two groups employed in the study were formed on the basis of the results from comprehensive neurological examinations performed at ages 1 and 7. Three discriminant function analyses were conducted, one for each scale separately and a third incorporating both scales using a stepwise procedure. Efficiency was measured in terms of number of correct and incorrect classifications, false positive and false negative errors, and validity coefficients. Comparisons among the analyses were examined by means of relative discrimination power and incremental validity. The findings suggested that the Motor Scale provides the most accurate identification of infants with suspected neurological impairments. A statistically significant likelihood discriminant function derived from both scales yielded some additional discriminative power. The law of parsimony, however, dictated the use of the single Motor Scale.
Sixteen patients with advanced rheumatoid arthritis who underwent total joint replacements of both hips and both knees were followed for an average of 22.8 months postoperatively. Their functional status before and after surgery was assessed by use of a special rating system for function. Fourteen of the 16 patients demonstrated higher total function scores at follow-up. Improvement was most marked in walking endurance, need for walking aids, and ability to climb stairs. Factors which were believed to predispose to less functional improvement included older age at initial surgery, longer duration of disease, more severe upper extremity involvement, and more frequent medical illnesses. There were 8 patients in whom combined hip and knee flexion in one or both lower extremities did not exceed 190 degrees after surgery. When this deficiency was combined with severe involvement of the upper extremities, difficulty with activities such as climbing stairs and arising from a chair was more common. Therefore, the goal of surgical treatment is to provide combined hip and knee flexion in excess of 190 degrees in these patients. Total joint arthroplasty has increased the likelihood of functional improvement in patients with severe rheumatoid arthritis involving the hips and knees, and encouraged the surgeon to operate earlier in the course of the disease as well as on patients with severely deformed joints.
Class III peroxidases (CIIIPRX) catalyze the oxidation of monolignols, generate radicals, and ultimately lead to the formation of lignin. In general, CIIIPRX genes encode a large number of isozymes with ranges of in vitro substrate specificities. In order to elucidate the mode of substrate specificity of these enzymes, we characterized one of the CIIIPRXs (PviPRX9) from switchgrass (Panicum virgatum), a strategic plant for second-generation biofuels. The crystal structure, kinetic experiments, molecular docking, as well as expression patterns of PviPRX9 across multiple tissues and treatments, along with its levels of coexpression with the majority of genes in the monolignol biosynthesis pathway, revealed the function of PviPRX9 in lignification. Significantly, our study suggested that PviPRX9 has the ability to oxidize a broad range of phenylpropanoids with rather similar efficiencies, which reflects its role in the fortification of cell walls during normal growth and root development and in response to insect feeding. Based on the observed interactions of phenylpropanoids in the active site and analysis of kinetics, a catalytic mechanism involving two water molecules and residues histidine-42, arginine-38, and serine-71 was proposed. In addition, proline-138 and gluntamine-140 at the 137P-X-P-X140 motif, leucine-66, proline-67, and asparagine-176 may account for the broad substrate specificity of PviPRX9. Taken together, these observations shed new light on the function and catalysis of PviPRX9 and potentially benefit efforts to improve biomass conservation properties in bioenergy and forage crops.
The three-parameter log-normal distribution (3PL) is an appropriate model for many of the continuous variables encountered in medicine. It is shown how to obtain different types of estimate and approximate (sometimes conservative) confidence intervals for the parameters of the 3PL and for certain functions of them, particularly in the calculation of reference ranges of clinical measurements. A simple non-iterative estimate of the shift parameter is described. The Shapiro-Wilk test of non-normality is modified to allow it to be used for testing for departure from the 3PL. Its power is compared with that of other well-known tests. The methods are illustrated using several data sets.
In an attempt to improve our understanding of the factors that affect human twinning, we further developed the models given by Hellin (1895) and Peller (1946). The connection between these models and our own model ("Fellman's law") were studied. These attempts have resulted in a more general model, which was then applied to data from Aland Islands (1750-1939), Nmes (1790-1875), Stuttgart (about 1790-1900) and Utah (1850-1900). The product of the mean sibship size and the total twinning rate can be considered as a crude estimate of the expected number of sets of twins in a sibship. The same can be said about the twinning parameter in our model. These estimates are in good agreement. If we consider twinning data only, we obtain the geometric distribution, and log (Nk), where Nk is the number of mothers with k twin maternities, is a linear function of the number of recurrences. Graphically, this property can easily be checked. For sibships containing three or more sets of twins, all four populations show higher values than expected, particularly the populations from Stuttgart and Utah, which data also show poor agreement according to a chi 2-test. A more exact model would demand more detailed demographic information, such as distribution of sibship sizes, age-specific twinning rates and temporal variations in twinning. The observed number of mothers in Aland with several recurrences of multiple maternities shows a considerable excess over the expected number as predicted by Peller's rule. The parameters in our model can be estimated by the maximum likelihood method and the obtained model fits the data better then Peller's model.
The death of a spouse has been described as the most disruptive and difficult role transition that an individual confronts throughout the life course. Using data from the 1984 and 1986 waves of the Longitudinal Study of Aging conducted by the National Center for Health Statistics, we examined the probability of moving associated with changes in functional disability levels over a two-year period while controlling for recent widowhood. We found that the greater the increase in instrumental disability between 1984 and 1986, the greater the probability of a move. We also found that the event of becoming a widow greatly increases the probability of a move when health declines.
Observing a clinical measurement for an individual is of little value, unless it can be compared with measurements obtained from a healthy population, thought of as standard. The range of measurements observed will, in general, vary with age or some function of time. The usual approach is to assume a distributional form for the population density, but this is inappropriate for variables which do not follow a simple distribution. A method of estimating the centiles of a conditional distribution using multi-dimensional kernel density estimation, to allow conditioning on the value of one or more covariates, is proposed. By careful choice of the kernel used, the percentiles may easily be calculated using a Newton-Raphson procedure. The method is illustrated using kidney lengths and birthweights of a sample of newborn infants.
This in vitro study measured the changes in the fracture resistance of posterior crowns as a function of crown length. The crowns, 10 for each group, were made of a feldspathic porcelain (Ceramco), a glass-ceramic material (Dicor), and an alumina-reinforced glass (In-Ceram). Three different crown lengths were tested on acrylic resin dies. The restorations were fractured in a testing machine using a steel ball, 12.7 mm in diameter, that contacted the occlusal surface at three distinct points. Statistical analysis was performed using the Weibull distribution. The fracture resistance increased significantly with increasing crown length for all crown materials.
De-hospitalization of cancer treatment, particularly for those with advanced disease, can complicate adjustment and strain the capacity of caregiver networks to meet patients' daily needs. Outpatient staff should be able to recognize patients who need help to meet their daily needs as well as those who are not getting enough help. This study describes the physiological and social determinants of need and unmet need for assistance among 629 cancer patients with advanced disease initiating a course of outpatient chemotherapy and/or radiation therapy. Areas of needs examined through telephone interviews with participating patients were: personal care, instrumental tasks (housework, shopping, and cooking), and transportation. Physiological factors (metastases, disease stage, and functional status) were associated with need for assistance in all three areas. Also, older age (over 65) and low income predicted need for help with personal care, and women were more likely than men to report illness-related need for assistance with instrumental tasks and transportation. Unmet need was primarily associated with patients' social support system (e.g., children living nearby and perceived resiliency of network helpers). These findings highlight the need for outpatient staff to evaluate patients' informal care resources as well as patients' symptoms and impairments in deciding who should be referred for home care services.
This article attempts to extend the generalizability of a three-dimensional model of self-reported physical health among the aged to a nonwestern culture. Consisting of three interrelated dimensions, chronic illness, functional status, and self-rated health, this model was empirically evaluated by using national data on the aged gathered in the United States and Japan. The three-dimensional specification was found to apply equally well to U.S. and Japanese elderly. In addition to examining the internal structure of this three-dimensional model, the study assessed the model's relationships with a set of selected exogenous variables including age, sex, marital status, and education. The relationships between the selected exogenous variables and physical health dimensions are largely similar in both countries. However, clear differences appeared in at least three instances.
The computer package QUAD has been developed at the University of Kent, U.K. It is menu driven and written in Advanced BASIC. It runs on IBM PC compatible machines equipped with a suitable graphics facility such as CGA or simulated CGA. QUAD is available on a floppy disk, for a small handling charge. QUAD has four main functions: it performs a logit analysis of quantal assay data; it provides a flexible way of analysing the data, allowing dose transformations and providing alternative confidence intervals for EDp values; it produces a range of diagnostics for assessing the fit of models to data; it provides and fits two families of extended models, each containing the logit as a special case. The package makes use of the latest statistical research, and fitted models are displayed by means of the good graphics facilities available on microcomputers. This document describes the facilities available in detail, and provides and discusses, illustrations of the package at work. QUAD has been designed as a pilot package. Further additions and developments are planned and described later.
Weight-age data from 50 Retinta beef cows from 8 to 97 mo of age located in southwestern Spain were fitted to von Bertalanffy, Brody, and Richards functions to determine the relationship between growth curve parameters and cow efficiency. Only cows having at least 31 weights were included in the analysis. Von Bertalanffy, Brody, and Richards functions were fitted to weights of each cow. Relevant parameters of the three functions are A and K, associated with the asymptotic mature weight and rate of maturing, respectively. Criteria for comparisons among the three functions were computing difficulty, goodness of fit, and lack of bias of A. Productivity indicators were number of calves weaned during the first five calving seasons (NC), average birth weight (BWT), average weaning weight (WW), and average weaning weight per cow per year (WWY). The von Bertalanffy function was selected as the most appropriate. Least squares means for A and K were 650 +/- 8.17 kg and .038 +/- .001 mo-1, respectively. The values of NC, BWT, WW, and WWY were 4.0 +/- .11 calves, 38.2 +/- .4 kg, 218 +/- 5 kg, and 172 +/- 5 kg, respectively. Regression analysis for A indicated a decrease in NC when mature weight increased (P less than .05). There was a nonsignificant trend for heavier cows (higher A) to have calves with heavier BWT or WW. The value of WWY increased (P less than .05) with increased maturing rate (K) of cows. No significant associations were found between K and BWT or WW.(ABSTRACT TRUNCATED AT 250 WORDS)
A biologically motivated breast cancer incidence rate function was fit to data from a published case-control study conducted in countries whose incidence is high (Wales and the United States), moderate (Brazil, Greece, and Yugoslavia), and low (Japan and Taiwan). The data include personal characteristics of 3,925 breast cancer cases and 11,327 controls interviewed in selected hospitals in 1964-1968. Parameters in the function specify the dependence of age-specific breast cancer incidence rates on age at menarche, age at menopause, occurrence and timing of full-term pregnancies, and body mass. Parameters were estimated separately for high-, moderate-, and low-risk countries. Examination of residuals provided little evidence of inadequacy of the fitted function in describing combined effects of the characteristics studied. The following patterns were seen in all three risk groups: 1) Incidence rates jump to a higher level after first childbirth, but then increase with age more slowly thereafter. 2) Rates increase with age more slowly after menopause than before. 3) Rates change quadratically with body mass index among all women, although the main trend varies: Rates decrease with body mass among premenopausal women in high-risk countries, but increase with body mass in all other groups of women. Similarities of parameter estimates across countries suggest that reproductive events and body fat exert similar effects on all women, regardless of breast cancer rates in their country of residence.