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Stage grouping of oropharyngeal cancer: evaluation of three systems by means of survival analysis.

Stage grouping is a method of summarizing multiple categories generated from the tumor, node, metastasis (TNM) classification system. Recently three different systems, the T and N integer score (TANIS), Hart, and 1997 Union Internationale Contre le Cancer systems, have been proposed. To verify their correlation to survival, a series of 64 patients affected by primary squamous cell carcinoma of the oropharynx was considered in this retrospective study. The data set was classified according to Union Internationale Contre le Cancer T stage and then grouped as recommended by the three systems. Results showed a crude survival rate of 28.13%. Univariate analysis by means of the logrank test yielded significant P values for the T and N integer score and Hart systems (0.0452 and 0.0179, respectively) and a borderline P value (0.0728) for the stratification based on the 1997 Union Internationale Contre le Cancer system. Multivariate analysis (Cox regression adjusted for age and sex) showed a significant correlation between the three staging systems and the mortality rate. Odds ratios were 1.36 (95% confidence interval, 1.12-1.66), 1.58 (95% confidence interval, 1.18-2.12), and 1.63 (95% confidence interval, 1.08-2.48) for the T and N integer score, Hart, and 1997 Union Internationale Contre le Cancer systems, respectively. The T and N integer score system showed the best statistical correlation, but a conclusive result could not be achieved because of the low number of patients in this study.

Adult↗

Subtyping of psychiatric patients by cluster analysis of QEEG.

We have previously reported successful classification of patients with a variety of psychiatric disorders, using multiple discriminant functions based upon selected neurometric QEEG variables. In independent replications, these functions accurately separate patients with different DSM-III-R diagnoses from one another and from normals. This capability demonstrates that distinctive and replicable patterns of neurometric abnormalities are correlated with the clinical symptom clusters upon which DSM-III-R diagnostic criteria are based. However, patients with the same clinical diagnoses often respond very differently to the same treatments. Similar symptoms may arise from different pathophysiology. This study explored the 'natural structure' of a population of psychiatric patients in 8 diagnostic categories, using uninformed cluster analysis based upon the same set of neurometric variables found useful in separating each of these categories from normal. This preliminary numerical taxonomic approach reveals that groups of patients in each of these DSM-III-R categories contain subtypes with markedly different pathophysiology; further, patients in different DSM-III-R categories were aggregated together within each cluster, displaying similar pathophysiological profiles. Objective classification based on such physiological measurements may add information useful to improve treatment outcomes.

Brain↗

Utilization of multiple imperfect assessments of the dependent variable in a logistic regression analysis.

Often, in biomedical research, there are multiple sources of imperfect information regarding a dichotomous variable of interest. For example, in a study we are conducting on the relationship between cocaine use and stroke risk, information on the cocaine use of each study patient is available from three fallible sources: patient interviews; urine toxicology testing, and medical record review. Regression analyses based on a rule for classifying patients from this information can result in biased estimation of associations and variances due to the misclassification of some subjects and to the assumption of certainty. We describe a likelihood-based method that directly incorporates multiple sources of information regarding an outcome variable into a regression analysis and takes into account the uncertainty in the classification. The method can be applied when some sources of information are missing for some subjects. We show how the availability of multiple sources can be exploited to generate estimates of the quality (for example, sensitivity and specificity) of each source and to model the degree to which missing data are informative. A fitting algorithm and issues of identifiability are discussed. We illustrate the method using data from our study.

Adult↗

Types of change: application of configural frequency analysis in repeated measurement designs.

Many researchers are concerned both with intraindividual change patterns and interindividual differences and similarities in those change patterns. Configural Frequency Analysis (CFA) provides a way to identify overrepresentations (types) and underrepresentations (antitypes) in the frequencies of multiple variable classifications organized to reflect patterns of change. Three methods of CFA for analyzing repeated measures data are considered. To establish trends, two of them require at least ordinal data and the third requires interval data. Data analysis and the interpretation of results are illustrated. CFA is compared with residual analysis from log-linear modeling.

Aging↗

Morphological associations between the Angle classes.

The association between the Angle classification and craniofacial form has been analysed with the aid of multiple linear regression analysis in a sample of 170 children, before orthodontic treatment had started. It was found that part of the differences between Class II, Class I, and Class III was accounted for by systematical variation in a coherent set of midface and cranial base dimensions. These variations were in harmony with each other: the cranial base angle Ba-S-N closed and the legs S-N and S-Ba shortened systematically from Class II, over Class I, to Class III. The juvenile mandible notably was not systematically different. Because the cranial base provides the framework for the maxilla to be built upon, it is concluded that in juveniles the midface above anything else creates the characteristic difference between the three Angle classes, not the mandible. The Angle classification of malocclusion, therefore, represents three arbitrary markers on a morphological continuum.

Adolescent↗

Identification of Leguminosae gums and evaluation of carob-guar mixtures by capillary zone electrophoresis of protein extracts.

A procedure for the extraction and capillary zone electrophoresis (CZE) separation of proteins from carob, guar and tara gums in a background electrolyte (BGE) of pH 9 containing 0.1% polyvinyl alcohol is described. The CZE protein profiles exhibit characteristic peaks for each one of the Leguminosae gums, which can be used to construct models capable of identifying samples of carob, guar and tara gums, and predicting the guar content in binary carob-guar mixtures of different geographical origin and harvested in different years. The classification and prediction models are constructed by using linear discriminant analysis (LDA) and multiple linear regression (MLR), respectively. An excellent resolution between the three categories is obtained with LDA, the model being capable of classifying samples with recognition and prediction capabilities of 100%. For MLR models constructed with carob-guar mixtures with and without a common history, the average of the calibration residuals are +/- 0.50 and +/- 0.90%, respectively (average values for the 2-20% guar range). For the later model, the detection limit was 3.2% guar (from the standard deviation of 18 mixtures with 2-4% guar, and for alpha = beta = 0.05).

Calibration↗

Magnetoencephalography: a tool for functional brain imaging.

At present, one of the most promising windows to the functional organization of the human brain is magnetoencephalography (MEG). By mapping the magnetic field distribution outside the head the sites of neural events can be located with an accuracy of a few millimeters and the temporal evolution of the activation can be traced with a millisecond resolution. This paper reviews some forward field calculation approaches suitable for the interpretation of the brain's electromagnetic signals. Inverse modelling with multiple dipoles is described in detail. An example of the analysis of the somatosensory evoked-responses illustrates the potential of multiple signal classification (MUSIC) algorithm in finding optimal dipole positions.

Algorithms↗

Ductal carcinoma in situ of the breast: a new phenotype classification system and its relation to prognosis.

In a study of invasive breast cancer, multiple correspondence analysis (MCA) revealed clustering of eight pathobiological variables. Two different phenotypes were distinguished by an index calculated on the basis of the variables (histologic grade, necrosis, lymphoid infiltration, number of mitosis and expression of c-erbB-2, p53, progesterone receptor and Bcl-2). Phenotype A lesions share most of the features of normal breast tissue. Phenotype B looks more malignant, has a higher early recurrence rate and is more frequently seen in younger patients. Our aim was to see if ductal breast carcinoma in situ (DCIS) could be divided into the same phenotypes. One hundred and eighty DCIS were investigated. Association between the eight variables was studied in 2 x 2 models. The phenotype index was calculated by summing weights for the variables in the MCA. All variables were associated, except Bcl-2. DCIS was divided in two phenotypes. Thirty-three tumours were Phenotype A and 147 Phenotype B. The mean age at diagnosis was 65.5 and 58.4 years for Phenotypes A and B, respectively (p = 0.0012). No difference regarding local relapse free survival was seen. Two phenotypes were distinguished in DCIS, similar to invasive breast cancer. In an earlier study, 45% of the invasive cancers were classified as Phenotype B. In this study, 82% of DCIS were Phenotype B. This may indicate that invasive breast cancer of Phenotype B is derived from DCIS of Phenotype B. The distribution of DCIS phenotypes with a small proportion of Phenotype A DCIS may be due to that Phenotype A DCIS is less likely to be detected by mammography, or that some invasive breast cancers of Phenotype A progress to invasiveness without passing the in situ phase.

Adult↗

Albumin-immunoglobulin complexes in human serum: classification and immunochemical analysis.

A complex between serum albumin and immunoglobulins was observed on immunoelectrophoresis in six patients. Two patients with multiple myeloma had monoclonal IgA-albumin complexes; one of these complexes was formed by covalent bonds and the other by non-covalent bonds. Four patients displayed non-covalent IgG-albumin complexes: of these, one had multiple myeloma, two had been treated with nitrofurantoin for prolonged periods, and one had diabetes mellitus. The IgG-albumin complex of the last patient was subjected to a detailed immunochemical analysis. The albumin-specific antibodies were isolated by affinity chromatography and analysed, using a sensitive tritium labelling technique. The antibodies were polyclonal, complexed with serum albumin through their Fab portion, and showed a high specificity for the human albumin as compared with bovine and rabbit albumins. The serum albumin of two patients displayed an abnormal behaviour in reduced SDS-polyacrylamide gel electrophoresis (PAGE). The abnormal albumins had an apparent molecular weight of 52,000 and could react with rabbit anti-human serum albumin like the normal protein. No abnormal albumin could be detected in 20 other patients' sera, including nitrofurantoin-treated patients and normal controls. These findings suggest a possible role for an altered self-component in the triggering of a specific autoimmune reaction.

Animals↗

Automated protein sequence database classification. I. Integration of compositional similarity search, local similarity search, and multiple sequence alignment.

MOTIVATION: Genome sequencing projects require the periodic application of analysis tools that can classify and multiply align related protein sequence domains. Full automation of this task requires an efficient integration of similarity and alignment techniques. RESULTS: We have developed a fully automated process that classifies entire protein sequence databases, resulting in alignment of the homologous sequences. The successive steps of the procedure are based on compositional and local sequence similarity searches followed by multiple sequence alignments. Global similarities are detected from the pairwise comparison of amino acid and dipeptide compositions of each protein. After the elimination of all but one sequence from each detected cluster of closely related proteins, the remaining sequences are compiled in a suffix tree which is self-compared to detect local sequence similarities. Sets of proteins which share similar sequence segments are then weighted according to their closeness and multiply aligned using a fast hierarchical dynamic programming algorithm. Computational strategies were devised to minimize computer processing time and memory space requirements. The accuracy of the sequence classifications has been evaluated for 12 462 primary structures distributed over 341 known families. The percentage of sequences with missed or incorrect family assignments was 6.8% on the test set. This low error level is only twice that of the manually constructed PROSITE database ( 3.4% ) and is substantially better than that found for the automatically built PRODOM database ( 34.9% ). AVAILABILITY: The resulting database, called DOMO, is available through database search routine SRS at Infobiogen (http://www.infobiogen.fr/srs5/), EBI (http://srs.ebi.ac.uk:5000/) and EMBL (http://www.embl-heidelberg.de/srs5/) World Wide Web sites. CONTACT: gracy@infobiogen.fr

Algorithms↗

Multiple synchronous colorectal carcinomas: a ploidy study by image analysis.

Cytometry could represent an ancillary technique to morphology in order to understand whether multiple synchronous colorectal carcinomas arose independently. Twenty-eight multiple synchronous tumours, assessed by means of a computerized image analysis system for DNA ploidy, were categorized as diploid (4) or not diploid (24). The ploidy classes were: DNA-diploid, DNA-tetraploid, and DNA-aneuploid. The DNA Index (DI) ranged from 0,90 to 2,66. The overall concordance rate for ploidy and DI class with synchronous tumours was 69% and 31%, respectively. The high concordance rate in ploidic categories suggests the metastatic origin of our multiple synchronous tumours. Moreover, they showed site, Dukes' classification, degree of differentiation, percentage of ploidy class, and DI distribution comparable to the single colorectal carcinomas. In conclusion, image analysis is a reliable technique to determine the independent clonality or the common origin of multiple colorectal tumours when the evaluation based on the simple histopathological criteria is not satisfactory.

Aged↗

Issues on functional analysis in behavioral assessment.

The rebirth of interest in functional analysis is described. Clarification among conflicting terms is offered as a way of facilitating research in the area. Three phases of functional approach to assessment are identified: (a) descriptive, (b) interpretive, and (c) verification. Five assessment methods common to assessment, generally, are shown to be useful in both descriptive and verification phases. Evaluation of functional approaches requires attention to the psychometric adequacy of these methods. Accuracy, reliability, and validity concepts are reviewed briefly and their application to functional strategies is described. The use of treatment validity in the functional analysis of functional analysis is mentioned as the ultimate strategy for evaluating the adequacy of this assessment approach. The paper ends with a discussion of problems of multiple control of behavior, behavioral classification systems, training parents and other mediators in the functional approach, cost-effectiveness, and the place of functional analysis in a reorganized health care delivery system.

Adult↗

Diagnosis and prognosis of renal-cell tumors: a molecular approach.

This review discusses the impact of molecular genetics on the diagnosis and prediction of the prognosis for renal-cell tumors. Through the use of molecular techniques, it has become possible to divide renal-cell tumors into genetically and biologically well-defined entities. The new classification has many advantages over morphological ones: (1) in contrary to tumor phenotype, genetic markers are constant during tumor progression and allow a precise diagnosis; (2) genetic analysis discriminates between papillary (multiple origin) and nonpapillary renal-cell carcinomas (solitary tumors); (3) genetic analysis allows a precise diagnosis of renal adenoma; (4) the new classification system offers a genetic prognostic system; and (5) the new diagnostic-prognostic system could easily be adapted to modern detection systems such as automated sequence and fragment-length analysis, which allow a quick and correct diagnosis with a high throughput.

Adenocarcinoma↗

Assessment of aortoiliac stenosis by femoral artery pressure measurement and Doppler waveform analysis.

Two-hundred and four aortoiliac segments of 102 patients with arterial disease of the legs were examined for evidence of aortoiliac stenosis by Doppler analysis of the common femoral artery, angiography and direct femoral artery pressure (FAP) measurements at rest and after induction of hyperaemia with papaverine. From the continuous wave and multigate Pulsed Doppler waveforms registered at rest and during postocclusion hyperaemia, the following instantaneous maximum frequency envelope parameters were calculated: maximum forward frequency, maximum reverse frequency, systolic upslope time (UST) and Pulsatility Index. The overall correlation of these parameters with the apriori classifications of the aortoiliac segments, based on FAP measurements and angiography, were poor. By multiple regression analysis the UST appeared to be the Doppler waveform parameter with the best predictive value for significant aortoiliac stenosis.

Aorta, Thoracic↗

[Multifactor analysis in prediction of outcome for ischemic stroke with combined cardiac symptomatology].

Basing on the results of multiple classifications of 70 clinical, paraclinical and anamnestic signs of ischemic stroke with combined cardiac symptomatology, the models predicting clinical outcome in acute period of the disease and an original scale of numerical score have been worked out. It is mathematically proved that the severity of ischemic stroke with combined cardiac symptomatology, scoring 75 and above, inevitably results in progression of fatal outcome. A group of unfavorable clinical predictors was singled out. The periods with high rate of fatal outcome within exacerbation of ischemic stroke and pathogenic types of stroke were studied. It is first-ever shown that a role of cardiac and neurological symptoms in predicting fatal outcome depends on ischemic stroke severity. A relation between the probable fatal outcome and dynamics of severity of stroke with combined cardiac symptomatology within the first 3 days of the disease was also revealed for the first time.

Adult↗

Classification and properties of 64 multiplexed microsphere sets.

We describe a practical method for the analysis of multiple analytes in a single sample. The vehicle for each separate measurement consists of a set of microspheres identifiable by characteristic fluorophores embedded in the particles. The use of robust, bench-top flow cytometers (flow microfluorimeters) for the analysis of the multiple sets of microspheres is facilitated by hardware and software, which acquire the data from the cytometer, classify the microspheres according to sets, and collate measurement information from each microsphere set in real time. This measurement system can analyze up to 64 analytes in a single sample. The advantages of multiplexed assays using flow cytometry include robust measurements, because each microsphere set is measured repeatedly. The advantage of the assay's is consistent with simultaneous measurement of many parameters as well as the speed with which the flow microfluorimeter (cytometer) makes measurements (many hundreds per second). Here, we describe the properties of the microspheres, the calibration of the cytometer, and the influence of the properties of the microspheres on the sensitivity of measurements.

Calibration↗