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PubMed1993

Systemic lupus erythematosus in Greece. Clinical features, evolution and outcome: a descriptive analysis of 292 patients.

The purpose of this study was the descriptive analysis of patients with systemic lupus erythematosus (SLE) with a particular focus on initial clinical features, evolution and outcome of disease, prevalence of clinical and serological manifestations and identification of clinicoserological associations indicative of renal and CNS involvement. The methodology applied was the following: retrospective analysis of the clinical charts of 292 unselected patients (246 female (84.2%) and 46 male (15.7%)) with SLE examined between 1982 and 1992. Multivariate analysis and hierarchical log linear models were used to examine for clinicoserological associations. Descriptive analysis was based on the prevalence of main clinicoserological features and disease outcome. The outcome was examined on the basis of the number of flares, the presence of chronic renal failure, the presence of central nervous system (CNS) involvement with subsequent disability and deaths. Flares were considered the severe alterations in disease status, requiring additional therapy to be controlled. The disease begins most frequently in the second and third decade of life with cutaneous and joint manifestations, while renal and CNS involvement developed later. The prevalence of serious renal, pulmonary and CNS involvement as well as the prevalence of RF, anti-Sm and anti-nRNP antibodies remain low. Multivariate analysis revealed the associations of renal involvement with leukopenia and serositis, of anti-Sm with leukopenia, of secondary Sjogren's syndrome with RF and of thromboembolic events with anticardiolipin antibodies. Patients with childhood onset SLE have a higher tendency for developing renal involvement than adult onset SLE patients. In addition, anti-Ro(SSA) antibodies were associated with anti-La(SSB) and RF, while anti-Sm antibodies were associated with anti-nRNP and RF. Flares occurred with a frequency of 0.07 per patient per year. Only 63.6% of flares were accompanied by positive anti-dsDNA reactivities. Reported deaths were 0.0047 per patient per year. Hierarchical log linear models indicated that the main variables of the disease were sufficient to describe our disease model and that the order of the interaction between the variables was insignificant. We conclude that the prevalence of various clinical features associated with SLE is similar, although the prevalence of CNS and pulmonary involvement as well as anti-Sm and anti-nRNP antibodies are less prominent in Greek SLE patients than that reported in the literature. The various clinicoserological associations detected do not appear to be of major significance as they are not powerful enough to subgroup the disease.

Adolescent↗
PubMed1996

Modelling of initial events and chemical behaviour of species induced in DNA units by Auger electrons from 125I, 123I and carbon.

Auger electron spectra for 123I and 125I generated by Monte Carlo calculation and Auger electrons emitted from carbon after photoelectric effect on its K-shell as well as two DNA models (linear plasmid and nucleosome model) based on x-ray diffraction experiments have been used to simulate the behaviour of all species and radicals created during the physical and the chemical phase of the Auger's transport. By introducing appropriate assumptions for the induction of strand breaks the number of these breaks can also be determined and correlated to experimentally found numbers of lethal events. Efficiency differences between the iodine nuclides themselves and in comparison with the rather monoenergetic Auger electrons from carbon are shown with regard to the direct and indirect effects on the two DNA models. The characteristic products in the physical, chemical and biochemical phase are compared with corresponding results from the literature for low-LET radiation.

Carbon↗
PubMed1997

Log-additive versus log-linear analysis of lead-contaminated house dust and children's blood-lead levels. Implications for residential dust-lead standards.

The Environmental Protection Agency has been mandated to develop a health-based standard for lead in residential dwellings in the United States. Prior estimates of the relationship between residential dust-lead levels and children's blood-lead concentrations have usually been obtained by using a log-linear regression of blood-lead concentration on levels of lead-contaminated house dust. It remains unknown, however, whether the log-linear model or a frequently cited alternative, the log-additive model, is the preferable regression method for analyzing these data. Secondary analysis of the Lead-in-Dust Study data was undertaken to compare log-additive with log-linear regression analysis for the purpose of developing a health-based dust lead standard. Specifically, we were interested in comparing the log-additive and log-linear analyses in their ability to characterize adequately the relationship of dust-lead loading on various surfaces with blood-lead concentrations among urban children and to develop a predictive model to estimate the risk that a child will develop an elevated blood-lead level on the basis of a known level of dust lead. We used two dust sampling methods, the Baltimore Repair and Maintenance (BRM) vacuum method and the wipe method, to compare the log-linear and log-additive models. The log-linear model was consistently superior to the log-additive model in its ability to explain the variability in the observed blood-lead concentrations of the studied children, for both the wipe sampler and the BRM sampler. In addition, the log-additive model often predicted only a limited increase in the probability of blood-lead concentrations exceeding 10 micrograms/dl as a result of doubling the dust-lead loading exposure, whereas the log-linear model consistently demonstrated a significant increase in the probability of blood-lead concentrations exceeding 10 micrograms/dl. BRM lead loading explained additional variability in blood lead above and beyond that explained by wipe loading for both carpeted and uncarpeted floors. In contrast, wipe-lead loading explained significant additional variability after adjustment for BRM loading for both uncarpeted floors and interior window sills. Although BRM loading better predicted children's blood-lead concentrations than did wipe loading, these differences were not statistically significant. We conclude that the log-linear model explained a greater percentage of the variability in blood-lead concentrations than did the log-additive model, indicating that the log-linear model should be the default model of choice for developing a dust-lead standard.

Air Pollution, Indoor↗
PubMed2001

Estimating effects of latent and measured genotypes in multilevel models.

Multilevel modelling is a data analysis technique for analysing linear models in samples with a hierarchical or clustered structure. Clustered data are often present in genetic research where family members may either be required or serve a methodological purpose to study hereditary factors. These samples imply a natural hierarchy because genetically related individuals are grouped within families. We first demonstrate the use of multilevel modelling to study latent genetic and environmental components of variance in extended families where subjects may be related as twins, full siblings, half siblings, or cousins. Next, measured genotypes are included to estimate locus effects. Because the model accounts for the clustering of observations by estimating a random intercept at the family level, it tests for genotype effects on the phenotype within families so that possible population stratification effects cannot cause false positive results. Several extensions are discussed such as testing for genotype-environment interactions, analysing different types of response scales, or tailoring the model to other sample structures. To illustrate the approach we used birth weight data of 5562 children from 3643 fathers from 3186 mothers in 2873 extended families to which simulated genotypes of a hypothetical locus were added.

Adult↗
PubMed1993

Highly sensitive object location in tissue models with linear in-phase and anti-phase multi-element optical arrays in one and two dimensions.

Based upon previous observations of low-frequency photon diffusion waves within highly scattering tissue, this paper explores the "near-field" phenomena of such waves of approximately 10-cm wavelength with 200-MHz phase modulation equipment. Multiple-element source arrays consist of laser diode sources modulated at 180 degrees out of phase with respect to the other sources. The diffusing waves originating from the out-of-phase sources give, in the midplane, an amplitude null and a sharp phase transition. These may be observed in a highly scattering intralipid medium simulating the breast or brain (0.5% intralipid), 3-5 cm from the transmitting laser diodes. In the plane containing the array, there is a high sensitivity for a small volume of a hidden absorber (indocyanine green) deep within a highly scattering medium; 20 pmol in a volume of 70 microliters can be detected. Two-dimensional arrays consisting of four or more elements in two orthogonal planes give sensitivity on both axes similar to the one-dimensional array. Measurements show that in the presence of a light-absorbing object, the amplitude null and the interference plane becomes a curved surface which is deflected toward the heterogeneity. The degree of deflection is related to the volume and the absorption characteristics of the heterogeneity and provides detection of the heterogeneity, and thereby may provide localization information for the detection of small tumors within the human breast, or stroke volumes, aneurysms, and tumors in the human brain.

Brain↗
PubMed1998

A real-time experimental prototype for enhancement of vision rehabilitation using auditory substitution.

The rehabilitation of blindness, using noninvasive methods, requires sensory substitution. A theoretical frame for sensory substitution has been proposed which consists of a model of the deprived sensory system connected to an inverse model of the substitutive sensory system. This paper addresses the feasibility of this conceptual model in the case of auditory substitution, and its implementation as a rough model of the retina connected to an inverse linear model of the cochlea. We have developed an experimental prototype. It aims at allowing optimization of the sensory substitution process. This prototype is based on a personal computer which is connected to a miniature head-fixed video camera and to headphones. A visual scene is captured. Image processing achieves edge detection and graded resolution. Each picture element (pixel) of the processed image is assigned a sinusoidal tone; weighted summation of these sinewaves builds up a complex auditory signal which is transduced by the headphones. On-line selection of various parameters and real-time functioning of the device allow optimization of parameters during psychophysical experimentations. Assessment of this implementation has been initiated, and has so far demonstrated prototype usefulness for pattern recognition. An integrated circuit of this system is to be developed.

Adaptation, Physiological↗
PubMed2006

Amygdalar volume and behavioral development in autism.

CONTEXT: The amygdala is associated with socioemotional function and has been implicated in the pathophysiology of autism. OBJECTIVE: To examine the relationship between amygdalar volume at ages 3 and 4 years and severity of clinical course and outcome at 6 years of age in children with autism spectrum disorder. DESIGN: Magnetic resonance images acquired at 3 and 4 years of age were used to measure total cerebral, amygdalar, and hippocampal volumes. Acquisition of social and communication skills was assessed semiannually using the Vineland Adaptive Behavior Scales. Hierarchical linear models were used to predict variability in individual linear growth trajectories as a function of IQ, total cerebral, and amygdalar or hippocampal volumes. SETTING: Longitudinal study of children with autism spectrum disorder. PARTICIPANTS: Forty-five children with autism spectrum disorders between 3 and 6 years of age. MAIN OUTCOME MEASURE: Linear growth trajectory of age equivalence Vineland communication and social scores. RESULTS: Larger right amygdalar volume was associated with more severe social and communication impairments at ages 3 and 4 years. Larger right amygdalar volume also was predictive of poorer social and communication abilities at age 6 years, even after controlling for IQ and total cerebral volume. Parallel analyses with hippocampal volumes found no relationship to social or communication development. CONCLUSIONS: Larger right amygdalar volume at 3 and 4 years of age, but not left amygdalar, hippocampal, or total cerebral volume, is associated with a more severe clinical course and worse outcome at age 6 years in children with autism spectrum disorder. These results provide additional evidence that amygdalar development is implicated in the behavioral impairments found in autism.

Amygdala↗
PubMed1998

The dynamics of prostate specific antigen in hormone refractory prostate carcinoma: an analysis of cancer and leukemia group B study 9181 of megestrol acetate.

BACKGROUND: Although many physicians measure serum prostate specific antigen (PSA) during the follow-up of patients with hormone refractory prostate carcinoma (HRPC), little has been done to formalize the determination of how these serial values of PSA impact on prognosis. To understand HRPC fully, make decisions about choices of treatment as well as about clinical research on treatments for HRPC patients, and design appropriate measures of PSA response, it seems that first it would be necessary to understand how these serial measures of PSA relate to survival. The purpose of this study was to determine how repeated measurements of PSA impact on the probability of imminent death for patients with HRPC. METHODS: One hundred forty-eight men with HRPC were enrolled in Cancer and Leukemia Group B Study 9181, in which they were treated with either a low dose (160 mg/day) or a high dose (640 mg/day) of megestrol acetate (MA). Because preliminary data analysis indicated that these treatments had no effect on survival, the authors pooled the data to analyze the overall dynamics of PSA and survival during the follow-up period. The authors attempted to correlate initial and monthly PSA measurements, which were mandated by the study protocol, with the probability of death at any time during follow-up. For statistical analysis, the Cox proportional hazards model and the general linear model were used. In addition to the level of PSA, the authors used the relative velocity of PSA, which was defined as (dy/dt)/y, with "y" symbolizing serum PSA and "t" symbolizing time. RESULTS: Both log(PSA) and the average relative velocity of PSA (rva) were significantly correlated with survival time (P=0.0001 and P=0.0008, respectively), and the analysis performed with the Cox proportional hazards model yielded the following formula for a PSA hazard score: PSA hazard score =0.251*(log(PSA) - mean log(PSA)) + 24.5*(rva - mean rva) This hazard score tended to be higher for patients who were about to die. For example, there was a close correlation between the hazard score and the probability of death as the next observed event. Furthermore, the hazard score provided a dynamic measure of how PSA was affected by treatment. CONCLUSIONS: The average relative velocity of PSA has been identified by the authors as a new measure of the dynamics of PSA in HRPC. It can be determined from sequential values of PSA. This average, together with the log(PSA), are significantly related to the probability of imminent death.

Antineoplastic Agents, Hormonal↗
PubMed2005

A Bayesian hierarchical non-linear regression model in receiver operating characteristic analysis of clustered continuous diagnostic data.

Receiver operating characteristic (ROC) analysis is a useful evaluative method of diagnostic accuracy. A Bayesian hierarchical nonlinear regression model for ROC analysis was developed. A validation analysis of diagnostic accuracy was conducted using prospective multi-center clinical trial prostate cancer biopsy data collected from three participating centers. The gold standard was based on radical prostatectomy to determine local and advanced disease. To evaluate the diagnostic performance of PSA level at fixed levels of Gleason score, a normality transformation was applied to the outcome data. A hierarchical regression analysis incorporating the effects of cluster (clinical center) and cancer risk (low, intermediate, and high) was performed, and the area under the ROC curve (AUC) was estimated.

Bayes Theorem↗
PubMed2004

Modelling relative survival using transformation methods.

Patient survival is often assessed as a measure of effectiveness of treatment in cancer clinical trials. The relative survival rate is a measure of patient survival corrected for the effect of other causes of death. We incorporate an additive hazards model for the overall force of mortality focusing attention on the form of the underlying disease process. Transformation models for the cause-specific hazard rate describing the disease process are considered. We demonstrate a method for estimating the transformation parameter providing insight into the appropriate choice of model structure. The models include the additive and multiplicative structures as special cases. We write the models in the generalized linear model framework and demonstrate ease of fitting via existing statistical software. The methodology is applied to a Hodgkin's disease data set to assess the effect of clinical trial results on population survival. Our analysis concludes that the multiplicative structure provides a more appropriate description of the data as compared to the additive structure.

Clinical Trials as Topic↗
PubMed1994

Another flaw in the linearized multistage model upper bounds on human cancer potency.

The statistical methodology used by the EPA and other federal agencies to characterize human cancer potencies based on animal experiments greatly exaggerates the estimates and bounds for human cancer risks in some instances. The current methodology incorporates simplified assumptions and approximations that fail to properly assess the impact of quantitative differences in human and experimental animal background transition rates from stage to stage in the multistage carcinogenic process. Because the majority of tumorigenic responses in rats and mice occur in organs with a high background tumor incidence and, hence, high background stage transition rates, the current simplified methodology often significantly overstates human risk. This newly recognized flaw in conjunction with the several previously recognized flaws in the current characterizations of human cancer potencies argues strongly for a change away from the current characterizations based solely on a default screening methodology to a more comprehensive, biologically based risk assessment methodology.

Animals↗
PubMed1987

A piecewise-linear growth model: comparison with competing forms in batch culture.

A simplified one-dimensional growth model based on the mass conservation law is proposed. Mathematically, it represents an easiest special case of so called L-systems. The model developed being considered as a descriptive tool of the growth curves is compared with four other similar and widely used models, in application to numerical data of bacteria (taken from literature) and of algae (an original experiment) growing in batch. Identification of free constants of the five models in comparison is performed using a nonlinear least squares iterative procedure, for which special programs were written. Theoretical and practical (approximative) merits of the new model are shown and discussed.

Bacteria↗
PubMed1987

A linear mathematical model for computerized analyses of mood curves. An empirical investigation on mood courses in depressive and schizophrenic inpatients.

The repetitious measurement of actual mood alterations becomes more and more common in research oriented psychiatric departments. In this article a new method for the mathematical description and statistical evaluation of time series data is presented. This computerized approach is less restrictive than other procedures and seems to be very appropriate to the complex structure of time series. First results on mood courses of depressive and schizophrenic patients are presented to demonstrate the usefulness and validity of this new method.

Computer Simulation↗
PubMed1979

A linear recirculation model for drug disposition.

A new approach to the modeling of drug disposition is described. Disposition is regarded as the result of repetitive passes of the drug around the circulation. Mathematical analysis of experimental blood concentration data yields an expression describing the kinetics of a single pass through the tissues. In physicochemical terms the single-pass behavior depends to a large extent on the interaction of the drug with individual tissues, which greatly simplifies interpretation. The method may reveal features of disposition not apparent from experimental blood concentration data.

Kinetics↗