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PubMed1997

Assessment of late results of surgery in talipes equino-varus: a reliability study.

UNLABELLED: The variability of a method for clinical and functional assessment of the long-term results of surgical correction of idiopathic congenital talipes equino varus was studied in ten boys and four girls (average age: 19.1 (SD 2.3 years); 22 affected feet) with radiographical evidence of fusion of the foot and ankle ossification centres. Patients were measured twice, 1 week-1 month apart, by the same investigator and were assessed twice on each visit. Assessment included anthropometry, functional assessment and subjective functional evaluation. Calf circumference, skinfold thickness, foot length and width were highly reproducible. Foot length was not significantly influenced by the operation whereas calf circumference, skinfold thickness and foot width were. Although highly reproducible, hopping was not significantly affected by operation. Active and passive range of motion were significantly different. Each was highly reproducible and both were significantly affected by the operation. Patients reported a high and highly reproducible (within two points) functional level. CONCLUSION: An assistant-administered functional questionnaire together with measurement of active and passive range of motion allows easy, valid and reproducible assessment of long-term results of surgery for idiopathic congenital talipes equino-varus correction. A significant effect of the number and type of operation was evidenced.

Adolescent↗

PubMed1995

Autoperception and satisfaction with health: two medical care markers in elderly hospitalized patients. Quality of life as an outcome estimate of clinical practice.

This paper reports a prospective study, carried out in elderly patients hospitalized for acute illness, designed to evaluate the effectiveness of medical treatment from the point of view of quality of life (QoL). Patient's autoperception and satisfaction with health, the most relevant subjective estimates of QoL, were assessed on admission to hospital and at check-up after discharge. A comprehensive functional evaluation of the patients was made. The results indicated an improvement in health autoperception coherent with the professional view. However, health satisfaction was not modified in any way after medical treatment. This dissonance could be explained because the predictors of satisfaction, age, sex, functional status and comorbidity, are the factors least modified by treatment. Satisfaction with ones own health could be a crucial marker of QoL especially for chronic diseases, but not appropriate for monitoring treatment effectiveness of acute illness. Health autoperception seems to be more desirable as an outcome estimate for this purpose.

Activities of Daily Living↗

PubMed2001

mROC: a computer program for combining tumour markers in predicting disease states.

Receiver operating characteristic (ROC) curves are limited when several diagnostic tests are available, mainly due to the problems of multiplicity and inter-relationships between the different tests. The program presented in this paper uses the generalised ROC criteria, as well as its confidence interval, obtained from the non-central F distribution, as a possible solution to this problem. This criterion corresponds to the best linear combination of the test for which the area under the ROC curve is maximal. Quantified marker values are assumed to follow a multivariate normal distribution but not necessarily with equal variances for two populations. Other options include Box-Cox variable transformations, QQ-plots, interactive graphics associated with changes in sensitivity and specificity as a function of the cut-off. We provide an example to illustrate the usefulness of data transformation and of how linear combination of markers can significantly improve discriminative power. This finding highlights potential difficulties with methods that reject individual markers based on univariate analyses.

Biomarkers, Tumor↗

PubMed2003

Structured antedependence models for genetic analysis of repeated measures on multiple quantitative traits.

Simultaneous analysis of correlated traits that change with time is an important issue in genetic analyses. Several methodologies have already been proposed for the genetic analysis of longitudinal data on single traits, in particular random regression and character process models. Although the latter proved, in most cases, to compare favourably to alternative approaches for analysis of single function-valued traits, they do not allow a straightforward extension to the multivariate case. In this paper, another methodology (structured antedependence models) is proposed, and methods are derived for the genetic analysis of two or more correlated function-valued traits. Multivariate analyses are presented of fertility and mortality in Drosophila and of milk, fat and protein yields in dairy cattle. These models offer a substantial flexibility for the correlation structure, even in the case of complex non-stationary patterns, and perform better than multivariate random regression models, with fewer parameters.

Animals↗

PubMed1995

Reducing nursing home use through community long-term care: an optimization analysis.

Can community services be made more effective in reducing nursing home use through better management of their mix and allocation? To test this idea, we used data from the National Long-Term Care Channeling Demonstration to estimate logistic regression models relating the use of various types of community services to nursing home use. We then used these estimates to form an objective function for a mathematical optimization procedure which minimizes total expected population nursing home use as a function of community service use, subject to a total expenditure constraint. We find through this simulated reallocation that, in theory, significant reductions in nursing home use can be produced without increasing total community expenditures.

Aged↗

PubMed1999

A multivariate test of interaction for use in clinical trials.

An important issue in clinical trials is whether the effect of treatment is essentially homogeneous as a function of baseline covariates. Covariates that have the potential for an interaction with treatment may be suspected on the basis of treatment mechanism or may be known risk factors, as it is often thought that the sickest patients may benefit most from treatment. If disease severity is more accurately determined by a collection of baseline covariates rather than a single risk factor, methods that examine each covariate in turn for interaction may be inadequate. We propose a procedure whereby treatment interaction is examined along a single severity index that is a linear combination of baseline covariates. Formally, we derive a likelihood ratio test based on the null beta0 = beta1 versus the alternative abeta0 = beta1, where X'beta(k) (k = 0, 1) corresponds to the severity index in arm k and X is a vector of baseline covariates. While our explicit test requires a Gaussian response, it can be readily implemented whenever the estimates of beta0,beta1 are approximately multivariate normal. For example, it is appropriate for large clinical trials where beta(k) is based on a logisitic or Cox regression of response on X.

Acarbose↗

PubMed2005

Correlational selection leads to genetic integration of body size and an attractive plumage trait in dark-eyed juncos.

When a trait's effect on fitness depends on its interaction with other traits, the resultant selection is correlational and may lead to the integration of functionally related traits. In relation to sexual selection, when an ornamental trait interacts with phenotypic quality to determine mating success, correlational sexual selection should generate genetic correlations between the ornament and quality, leading to the evolution of honest signals. Despite its potential importance in the evolution of signal honesty, correlational sexual selection has rarely been measured in natural populations. In the dark-eyed junco (Junco hyemalis), males with experimentally elevated values of a plumage trait (whiteness in the tail or "tail white") are more attractive to females and dominant in aggressive encounters over resources. We used restricted maximum-likelihood analysis of a long-term dataset to measure the heritability of tail white and two components of body size (wing length and tail length), as well as genetic correlations between pairs of these traits. We then used multiple regression to assess directional, quadratic, and correlational selection as they acted on tail white and body size via four components of lifetime fitness (juvenile and adult survival, mating success, and fecundity). We found a positive genetic correlation between tail white and body size (as measured by wing length), which indicates past correlational selection. Correlational selection, which was largely due to sexual selection on males, was also found to be currently acting on the same pair of traits. Larger males with whiter tails sired young with more females, most likely due to a combination of female choice, which favors males with whiter tails, and male-male competition, which favors both tail white and larger body size. To our knowledge, this is the first study to show both genetic correlations between sexually selected traits and currently acting correlational sexual selection, and we suggest that correlational sexual selection frequently may be an important mechanism for maintaining the honesty of sexual signals.

Animals↗

PubMed1994

Median time from seroconversion to AIDS in Italian HIV-positive haemophiliacs: different parametric estimates.

The purpose of this study was to estimate the median incubation time between human immunodeficiency virus (HIV) infection and onset of acquired immunodeficiency syndrome (AIDS), using three parametric models and six estimates of seroconversion time. Study subjects were 732 HIV-positive haemophiliacs enrolled in the Italian Registry of patients with congenital coagulation disorders. Seroconversion time was estimated for each subject according to six different criteria, based on three distributions of seroconversion (uniform, uniform on three sub-intervals and truncated Weibull) and two indices synthesizing each distribution (median and median of three random values). The estimated seroconversion times were subsequently used as starting points in the analysis of incubation. This was performed applying Kaplan-Meier non-parametric survival analysis, and fitting to incubation data three probability density functions, representing three different situations with respect to the hazard of developing AIDS following seroconversion (namely Weibull (WE), generalized exponential (GE) and log-logistic (LL)). The cumulative incidence over an 8-year period ranged from 14.9 to 17.8 per cent when applying the Kaplan-Meier method, from 14.1 to 17.2 per cent when using the WE function, from 14.5 to 17.3 per cent when using the GE function and from 14.4 to 17.3 per cent when using the LL function, depending on the estimate of seroconversion time used. Similarly, the median incubation times ranged from 12.6 to 15.0 years with the WE function, from 14.0 to 16.5 years with the GE function, and from 13.4 to 16.1 years with the LL function. The presence of a bound on the increase of the hazard function seems to affect the incubation more strongly than the eventual decrease following the attainment of the maximum risk. This may be due to the decrease in the hazard beginning when most of the seropositive subjects have already developed AIDS.

Acquired Immunodeficiency Syndrome↗

PubMed1995

The restricted cubic spline as baseline hazard in the proportional hazards model with step function time-dependent covariables.

We incorporate a cubic spline function where the tails are linearly constrained, as the baseline hazard, into the proportional hazards model. We show estimation of covariable coefficients and survival probabilities with this model to be as efficient statistically as with the Cox proportional hazards model when covariables are fixed. Examples show that the inclusion of time-dependent covariables defined as step functions into the restricted cubic spline proportional hazards model reduces computation time by a factor of 213 over the Cox model. Advantages of the spline model also include flexibility of the hazard, smooth survival curves, and confidence limits for the survival and hazard estimates when there are time-dependent covariables present.

Coronary Artery Bypass↗

PubMedDate not supplied

Bilateral total hip and knee replacement in adults with rheumatoid arthritis: an evaluation of function.

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.

Adult↗

PubMed2002

Characterisation of two snail genes in the gastropod mollusc Patella vulgata. Implications for understanding the ancestral function of the snail-related genes in Bilateria.

Snail genes have been found to play a role in mesoderm formation in two of the three clades of bilaterians, deuterostomes (comprising the chordates) and ecdysozoans (comprising the arthropods). No clear data are available on the role these genes play in development of the mesoderm in the third clade, that of lophotrochozoans (comprising annelids and molluscs). We identified two new members of the snail gene family in the gastropod mollusc Patella vulgata. Phylogenetic analysis showed that the two genes clearly belong to the snail sub-family. Their expression patterns do not indicate a role during early mesoderm formation. In fact, contrary to expectations, the snail genes of Patella were mostly expressed in the ectoderm. In view of the location of their expression sites, we suggest that these genes could be involved in regulating epithelial-mesenchymal transitions (EMT) and cell motility, as has recently been demonstrated for snail genes in vertebrates. This may well correspond to the ancestral function of these genes. The results are discussed in the light of the evolutionary origin of the mesoderm. Electronic supplementary material to this paper can be obtained by using the Springer LINK server located at http://dx.doi.org/10.1007/s00427-002-0228-1.

Amino Acid Sequence↗

PubMed2001

Upper bound of the expected training error of neural network regression for a Gaussian noise sequence.

In neural network regression problems, often referred to as additive noise models, NIC (Network Information Criterion) has been proposed as a general model selection criterion to determine the optimal network size with high generalization performance. Although NIC has been derived using asymptotic expansion, it has been pointed out that this technique cannot be applied under the assumption that a target function is in a family of assumed networks and the family is not minimal for representing the target true function, i.e. the overrealizable case, in which NIC reduces to the well-known AIC (Akaike Information Criterion) and others depending on a loss function. Because NIC is the unbiased estimator of generalization error based on training error, it is required to derive the expectations of errors for neural networks for such cases. This paper gives upper bounds of the expectations of training errors with respect to the distribution of training data, which we call the expected training error, for some types of networks under the squared error loss. In the overrealizable case, because the errors are determined by fitting properties of networks to noise components, including in data, the target set of data is taken to be a Gaussian noise sequence. For radial basis function networks and 3-layered neural networks with bell shaped activation function in the hidden layer, the expected training error is bounded above by sigma2* - 2nsigma2*logT/T, where sigma2* is the variance of noise, n is the number of basis functions or the number of hidden units and T is the number of data. Furthermore, for 3-layered neural networks with sigmoidal activation function in the hidden layer, we obtained the upper bound of sigma2* - O(log T/T) when n > 2. If the number of data is large enough, these bounds of the expected training error are smaller than sigma2* - N(n)sigma2*/T as evaluated in NIC, where N(n) is the number of all network parameters.

Analysis of Variance↗

PubMed1998

The dynamics of dimensions of age-related disability 1982 to 1994 in the U.S. elderly population.

Declines in chronic disability were observed in the National Long Term Care Survey (NLTCS) 1982 to 1994. We analyzed the 1982, 1984, 1989, and 1994 NLTCS to identify the dimensions of chronic disability from multivariate analyses of a rich battery of measures of the ability (or inability) to perform specific activities. Changes over time in the prevalence of individual disability dimensions can be tracked to evaluate the rate of age-related losses of specific functions, 1982-1994. Seven dimensions described changes in the age dependence of 27 activities of daily living, instrumental activities of daily living, and physical performance measures in community and institutional resident elderly individuals over the 12 year period. Adjusted for age, the healthiest dimension with the best physical function experienced the largest increase in prevalence (3.3%) implying a decline in age-related disability. Disability declines were correlated with reductions in select health conditions (e.g., dementia and circulatory disease) over the study period.

Activities of Daily Living↗

PubMed2001

Readmission to the intensive care unit after liver transplantation.

OBJECTIVE: We undertook this study to understand the factors at our transplant center that contribute to patients' return to the ICU after their liver transplant and their initial discharge from that unit. Patients who, after liver transplantation, fail discharge from the Intensive Care Unit (ICU) and must be readmitted to that unit may well utilize many more resources than those patients who are well enough to stay out of the ICU. DESIGN: A retrospective review of a prospectively maintained liver transplant research database followed by a retrospective review of (a subgroup) patient charts and contemporaneous controls. SETTING: A large metropolitan tertiary care center and adult liver transplant center. PATIENTS: A total of 1,197 consecutive adult patients who underwent their initial liver transplantation from 1984 to 1996. INTERVENTION: Readmission to the intensive care unit after adult liver transplantation and discharge from that unit. MAIN RESULTS: Only recipient age, pretransplant synthetic function labs (protime and albumin), bilirubin levels, and intraoperative blood product requirements could be statistically linked to the group requiring ICU readmission. The primary etiology for ICU readmission was cardiopulmonary deterioration. Readmission was associated with significantly lower patient and graft survivals. A detailed review of 23 patients transplanted from October 1994 to June 1996 was made, with special emphasis on cardiopulmonary status (hemodynamics, respiratory variables, and chest radiograph findings). This subgroup was compared with 30 temporally matched controls who were not readmitted to the ICU. Intravascular fluid overload and lower inspiratory capacity were significant factors related to ICU readmission. Readmitted patients had a longer hospitalization with higher hospital charges than the control group. CONCLUSIONS: We conclude that the most important means of preventing ICU readmission in liver transplantation patients is to optimize cardiopulmonary function and status. Close monitoring of fluid balance to avoid hypervolemia is essential. Readmitted patients have a greater resource utilization and have lower survival rates.

Adult↗

PubMed2016

Characterization of Class III Peroxidases from Switchgrass.

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.

Amino Acid Sequence↗

PubMed1999

Characteristics of visual feedback in postural control during standing.

In the present study, the visual feedback system in postural control was investigated. To suppress the vestibular and proprioceptive feedback paths, a subject stood on a force-measuring plate with a fixed back support. Because the subject's body was immovable under these conditions, the subject controlled a computer model which simulated body dynamics. Information on the sway angle of the model was fed visually. Under this condition, frequency response functions for the ankle moment in response to the sway angle were calculated. The experimental results suggest that the visual feedback system contains a large time delay and, consequently, the visual system does not by itself allow a subject to maintain an upright posture. Index Terms- Feedback control, frequency characteristics, identification, posture, visual sensory feedback.

Adult↗

PubMed2005

The evolution of male genitalia: patterns of genetic variation and covariation in the genital sclerites of the dung beetle Onthophagus taurus.

Three main hypotheses, have been invoked to explain divergent genital evolution, the lock and key, pleiotropy, and sexual selection hypotheses, each of which make different predictions about how genital traits are inherited. Here we used a half-sib breeding design to examine the patterns of genetic variation and covariation between male genital sclerites, and their covariance with general body morphology in the dung beetle Onthophagus taurus. We found CV(A)'s and CV(P)'s were similar for both genital and general morphological traits and that CV(R)'s were large for both trait types. We found that male genital sclerites were negatively genetically correlated with general morphological traits. Variation in male genital morphology has direct implications for a male's fertilization success and the resulting sexual selection acting on male genitalia is predicted to maintain high levels of additive genetic variance. Contrary to this prediction, we found that individual genital sclerites all had low levels of additive genetic variance and large maternal and environmental sources of variation. Our data suggest that the genital sclerites in O. taurus are not inherited independently but as a genetically integrated unit. More importantly, the way the different sclerites function to influence male fertilization success reflects this genetic integration. Even though levels of V(A) in individual genital sclerites may be low, there may still be sufficient V(A) in multivariate trait space for selection to generate evolutionary change in the overall morphology of male genitalia.

Animals↗

PubMed2006

Search for a common cause factor amongst cognitive, speed and biological variables using narrow age cohorts.

BACKGROUND: Cross-sectional studies have demonstrated that age-related effects on many cognitive and biological functioning variables are shared. A number of theories postulate that these associations arise from a common causal mechanism responsible for change across a wide range of functions. However, it has been claimed that the finding of shared variance among variables in these studies may be spurious because most studies have been cross-sectional and based on age-heterogeneous samples. OBJECTIVE: To examine evidence for changes with age in variance shared by cognitive variables using a narrow-age cohort design. METHODS: Three samples of adults with age ranges 20-24 years (n = 2,404), 40-44 years (n = 2,530) and 60-64 years (n = 2,510) were drawn from a population-based study. These groups were supplemented by data from an older sample of individuals (77 years and over) from a second population-based study (n = 374). Four models of the structure of a range of cognitive, speed and biological variables derived from previous cross-sectional research were fitted to data. These models were complete independence of variables within a cohort, a single common factor, multiple independent factors, and a second order factor model. RESULTS: Model fit and the magnitude of loadings from multiple-group confirmatory factor analyses was compared between age groups. The fit for all four models was worse in the 60-64 year age group. Factor loadings on the common factor specified in these models varied between the groups, but the speed factor rather than the biological factor showed increased loadings as a function of age. CONCLUSIONS: This narrow age-cohort study did not support the existence of developmental changes in the structure of cognitive and biological variables across the lifespan. Shared variation between measures of cognition and biological function may be an artifact of the research designs that have generated these findings. This casts doubt of the existence of a common causal mechanism. However, it may be that such changes manifest only in later old age.

Adult↗