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PubMed2002

A comprehensive and novel predictive modeling technique using detailed pathology factors in men with localized prostate carcinoma.

BACKGROUND: The purpose of the current study was to evaluate modeling strategies using sextant core prostate biopsy specimen data that would best predict biochemical control in patients with localized prostate carcinoma treated with permanent prostate brachytherapy (PPB). METHODS: One thousand four hundred seventy-seven patients underwent PPB between 1992 and 2000. The authors restricted analysis to those patients who had sextant biopsies (n = 1073). A central pathology review was undertaken on all specimens. Treatment consisted of PPB with either I-125 or Pd-103 prescribed to 144 Gy or 140 Gy, respectively. Two hundred twenty-eight patients (21%) received PPB in combination with external radiotherapy and 333 patients (31%) received neoadjuvant hormones. In addition to clinical stage, biopsy Gleason sum, and pretreatment prostate specific antigen (pretx-PSA), the following detailed biopsy variables were considered: mean percentage of cancer in an involved core; maximum percentage of cancer; mean primary and secondary Gleason grades; maximum Gleason grade (primary or secondary); percentage of cancer in the apex, mid, and base; percent of cores positive; maximum primary and secondary Gleason grades in apex, mid, and base; maximum percent cancer in apex, mid, and base; maximum Gleason grade in apex, mid, and base; maximum primary Gleason grade; and maximum secondary Gleason grade. In all, 23 biopsy variables were considered. Four modeling strategies were compared. As a base model, the authors considered the pretx-PSA, clinical stage, and biopsy Gleason sum as predictors. For the second model, the authors added percent of cores positive. The third modeling strategy was to use stepwise variable selection to select only those variables (from the total pool of 26) that were statistically significant. The fourth strategy was to apply principal components analysis, which has theoretical advantages over the other strategies. Principal components analysis creates component scores that account for maximum variance in the predictors. RESULTS: The median followup of the study cohort was 36 months (range, 6-92), and the Kattan modification of the American Society for Therapeutic Radiology and Oncology (ASTRO) definition was used to define PSA freedom from recurrence (PSA-FFR). The four models were compared in their ability to predict PSA-FFR as measured by the Somers D rank correlation coefficient. The Somers D rank correlation coefficients were then corrected for optimism with use of bootstrapping. The results for the four models were 0.32, 0.34, 0.37, and 0.39, respectively. CONCLUSIONS: The current study shows that the use of principal components analysis with additional pathology data is a more discriminating model in predicting outcome in prostate carcinoma than other conventional methods and can also be used to model outcome predictions for patients treated with radical prostatectomy and external beam.

Adult↗
PubMed1993

The structure and correlates of alcohol dependence: WHO collaborative project on the early detection of persons with harmful alcohol consumption--III.

The cross-cultural validity of the Alcohol Dependence Syndrome was tested on 13 symptoms of alcohol dependence which were assessed as part of a WHO collaborative study of the early detection of harmful drinking. The subjects were drinking patients in health care settings in Australia, Bulgaria, Kenya, Mexico, Norway, and the US. Principal Components Analyses were performed on the symptoms in each centre, and the degree of agreement between the results was assessed by calculating coefficients of congruence between the item loadings on the first principal component. In all six centres the first Principal Component accounted for at least half of the total variance and all symptoms had positive loadings greater than 0.40 on the first Principal Component. The coefficients of congruence were all 0.98 or more, and the 13 symptoms had internal consistency coefficients of 0.94 or more. An alcohol dependence score defined by the sum of positive responses to the 13 alcohol dependence symptoms was positively correlated with self-reported alcohol consumption, alcohol-related problems, serum gamma glutamyltransferase and a clinical examination assessment of alcoholism in all six samples.

Adolescent↗
PubMed2004

An excitement subscale of the Positive and Negative Syndrome Scale.

BACKGROUND: We sought to develop and validate an excitement subscale from the Positive and Negative Syndrome Scale (PANSS) to allow the investigation of mania-like excitement symptoms in clinical trials of patients with schizophrenia using the PANSS and to provide clinicians with a short assessment tool for these states. METHODS: Baseline PANSS data from six double-blind, randomized registration trials of olanzapine, three in schizophrenia and three in acute bipolar mania, were used in these post-hoc analyses. Schizophrenia study data were pooled and randomly split in half. Exploratory principal component factor analysis was performed on half of the data. Factors were extracted based on minimum eigenvalue criteria (eigenvalue> or =1); loadings were determined using an equamax rotation. Confirmatory principal component factor analysis was performed on the other half of the data, retaining the original number of factors. Principal component factor analysis was also done for the pooled bipolar studies. Change in the new mania-like factor scores was then correlated with Young Mania Rating Scale (Y-MRS) scores in each bipolar study. RESULTS: Exploratory principal components analysis on the pooled schizophrenia data extracted five factors: negative, positive, excitement, cognitive, and depressive factors. The mania-like excitement factor was represented by four items (uncooperativeness, poor impulse control, excitement, and hostility), with only moderate loadings by tension and suspiciousness/persecution. Results were similar in the confirmatory analysis and the pooled bipolar studies. Change from baseline to endpoint for the mania-like factor correlated reasonably well (0.64-0.78) with change in Y-MRS scores in the bipolar studies. At baseline, bipolar patients scored higher than patients with schizophrenia on three of four PANSS mania-like factor items: poor impulse control, excitement, and hostility; the converse was true for most other PANSS items. CONCLUSION: Factor analyses of the PANSS consistently uncovered an excitement factor including uncooperativeness, poor impulse control, excitement, and hostility items. This factor may be useful in examining manic symptoms in studies where the addition of a scale specific to mania would be burdensome and where symptoms of excitement are part of the clinical presentation.

Adolescent↗
PubMed2007

The coupling between upper and lower extremity synergies during whole body reaching.

When performing whole body reaching movements, all four limbs participate in the task. We hypothesized that the synergies that characterize upper and lower extremity movement are flexible and become coupled into one functional unit to transport the body towards the target. To test this hypothesis, subjects reached to three targets, one within and two beyond arm's length. In addition, subjects reached at two speeds and either stopped at the target or returned to the original start position. To assess the coupling during the various whole body reaches, a principal component analysis was performed on the displacements of the five primary joints used to accomplish the task (ankle, knee, hip, shoulder and elbow). Analysis of the loadings from the principal component analysis indicated that the first component represented the reaching element of the task, while the second and third components represented the postural element. When reaching within arm's length the variance explained by the joint coupling was distributed between the first three principal components. However, as reach distance increased, the distribution shifted with most of the variance being explained by the first principal component. Neither movement velocity nor final joint configuration affected the coupling between the joints. Analysis of center of mass indicated that it shifted progressively forward as reached distance increased. We conclude that as target distance increased, the reach and postural synergies became coupled resulting in the arms, legs and trunk working together as one functional unit to move the whole body forward.

Adult↗
PubMed2001

Stability of adiposity phenotypes from childhood and adolescence into young adulthood with contribution of parental measures.

OBJECTIVE: The stability of several indicators of body composition and adipose tissue distribution over 12 years was quantified. RESEARCH METHODS AND PROCEDURES: The participants were 77 boys and 76 girls who were evaluated along with their parents at baseline as children and adolescents (8 to 18 years of age) and remeasured as young adults 12 years later. Indicators of body composition included the body mass index, fat mass, fat free mass, percentage of body fat, sum of six skinfolds (SF6), and the first principal component of six age-adjusted skinfold residuals. Relative adipose tissue distribution was represented by the second principal component of skinfold residuals and a trunk-to-extremity skinfold ratio, adjusted for SF6. RESULTS: Partial interage correlations, controlling for initial age and length of follow-up, were 0.65 and 0.59 for the body mass index, 0.59 and 0.64 for fat mass, 0.65 and 0.57 for fat free mass, 0.50 and 0.57 for percentage of body fat, 0.66 and 0.44 for SF6, 0.64 and 0.42 for the first principal component of six age-adjusted skinfold residuals, 0.19 and 0.31 for the second principal component of skinfold residuals, and 0.41 and 0.47 for trunk-to-extremity skinfold ratio, adjusted for SF6, in men and women, respectively. Multiple regression analyses indicated that the significant partial R(2) values of parental measurements on the prediction of their offspring in young adulthood ranged from 2% to 9%. DISCUSSION: The results indicate moderately high stability of indicators of body composition and somewhat lower stability of measures of adipose tissue distribution. Overall, parental measures offer less predictive value than do measures of childhood and adolescent body composition and adipose tissue distribution.

Adipose Tissue↗
PubMed1999

Reorganized cerebral metabolic interactions in temporal lobe epilepsy.

Patients with left temporal lobe epilepsy demonstrate language impairments that are not well understood. To explore abnormal patterns of brain functional connections with respect to language processing, we applied a principal component analysis to resting regional cerebral metabolic data obtained with positron emission tomography in patients with right- and left-sided temporal lobe epilepsy and controls. Two principal components were expressed differentially among the groups. One principal component comprised a pattern of metabolic interactions involving left inferior frontal and left superior temporal regions-corresponding to Broca's and Wernicke's areas, respectively-and right mesial temporal cortex and right thalamus. Functional couplings between these brain regions were abnormally enhanced in the left-sided epilepsy patients. The right thalamic left superior temporal coupling was also abnormally enhanced in the right-sided epilepsy patients, but differentially from that in the left-sided patients. The other principal component was characterized by a pattern of metabolic interactions involving right and left mid prefrontal and right superior temporal cortex. Although both the right- and left-sided epilepsy patients showed decreased functional couplings between left mid prefrontal and the other brain regions, a weaker right-left mid prefrontal coupling in the left-sided epilepsy patients best distinguished them from the right-sided patients. The two mutually independent, abnormal metabolic patterns each predicted verbal intelligence deficits in the patients. The findings suggest a site-dependent reorganization of two independent, language-subserving pathways in temporal lobe epilepsy.

Adolescent↗
PubMed1998

Automatic quantification of immunohistochemically stained cell nuclei using unsupervised image analysis.

A method for quantification of images of immunohistochemically stained cell nuclei by computing area proportions is presented. The image is transformed by a principal component transform. The resulting first component image is used to segment the objects from the background using dynamic thresholding of the P2/A-histogram, where P2/A is a global roundness measure. Then the image is transformed into principal component hue, defined as the angle around the first principal component. This image is used to segment positive and negative objects. The method is fully automatic and the principal component approach makes it robust with respect to illumination and focus settings. An independent test set consisting of images grabbed with different focus and illumination for each field of view was used to test the method, and the proposed method showed less variation than the intraoperator variation using supervised Maximum Likelihood classification.

Algorithms↗
PubMed2004

Comparison of the usefulness of the MTT, ATP, and calcein assays to predict the potency of cytotoxic agents in various human cancer cell lines.

Cell viability assays are important tools in oncological research and clinical practice to assess the tumor cell sensitivity of individual patients. The purpose of this study was to demonstrate the comparability of 3 widely used assays (MTT, ATP, calcein assays) by principal component analysis. The study included 4 different cytostatics (cisplatin, docetaxel, doxorubicin, vinblastine) and 3 different human cancer cell lines (MCF-7, A2780, doxorubicin resistant A2780adr). Ninety-three percent of the total variance of all variables included in the principal component analysis (resulting from 3 cell lines and 3 assays) could be explained by 1 principal component. Factor loadings were > 0.937 except for the variable MTT-A2780adr, which was 0.872. These results indicate the similarity of the 3 assays. A 2nd principal component analysis included literature data and showed accordance of data from this study and the literature. The MTT assay was further improved as a high-throughput screening-capable assay. The ATP assay is able to detect effects of cytostatics already after 1 h incubation. The determination of resistance factors allowed to differentiate cytostatics into P-gp or non-P-gp substrates. In conclusion, this study provides improved microplate reader-based cell viability assays and sets a statistically solid basis for a future comparison of data obtained in different laboratories by any of the 3 assays.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1996

[Screening of high-risk population susceptible to stroke and their characteristics].

High-risk population susceptible to stroke were screened with self-designed scoring method for quantitatively evaluating the risk of stroke in 550,000 frame population in 22 areas with different incidence of stroke during 1990-1993 and its related factors were analyzed by a principal component analysis method. Results showed scoring value correlated positively with probabilities of stroke, which suggested its objectivity and feasibility. The first principal component correlated positively with age, blood pressure, blood sugar, blood cholesterol, body mass index, ect., which reflected the characteristics of high risk population susceptible to stroke, and 71.43% of those with stroke were in the first principal component class. The proportion of the population with the first principal component correlated positively with the incidence of stroke in the area, therefore, stroke prevention should be focused on such population.

Adult↗
PubMed1994

Use of multivariate analysis to compare antimicrobial agents on the basis of in vitro activity data.

Multivariate techniques such as principal component analysis or similar factor analysis help in analyses of the simultaneous interrelationships among several variables. A comparative multivariate analysis on the in vitro activities of eight antimicrobial agents, including the novel molecule daptomycin, is presented. Multivariate analysis detects components or factors and establishes connections among antimicrobial agents on the basis of their different levels of participation in each factor. The first principal component was dominated by vancomycin, teicoplanin, and rifampin (0.94344, 0.92792, and 0.72127, respectively). The second principal component showed strong effects from imipenem, gentamicin, and cephalothin (0.87922, 0.86126, and 0.68870, respectively). Daptomycin stood out alone in the third principal component (0.83983). The first three components defined 81.5% of the total variance and could easily be represented graphically in a three-dimensional scatter plot. In this graphic representation, the eight antimicrobial agents clustered in three different spatial regions; daptomycin occupied a separate spatial position. The use of multivariate analysis offers a different approach to determination of the in vitro activities of new antimicrobial agents and adds some new data on the relationships among different classes. Notwithstanding its limitations, the application of these methods in microbiology and drug development could be an additional tool for use in processing information.

Anti-Bacterial Agents↗
PubMed2002

Patterns of hand motion during grasping and the influence of sensory guidance.

This study was aimed at describing temporal synergies of hand movement and determining the influence of sensory cues on the control of these synergies. Subjects were asked to reach to and grasp various objects under three experimental conditions: (1) memory-guided movements, in which the object was not in view during the movement; (2) virtual object, in which a virtual image of the object was in view but the object was not physically present; and (3) real object, in which the object was in view and physically present. Motion of the arm and of 15 degrees of freedom of the hand was recorded. A principal components analysis was developed to provide a concise description of the spatiotemporal patterns underlying the motion. Vision of the object during the reaching movement had no influence on the kinematics, and the effect of the physical presence of the object became manifest primarily after the fingers had contacted the object. Two principal components accounted for >75% of the variance. For both components, there was a strong positive correlation in the rotations of metacarpophalangeal and proximal interphalangeal joints of the fingers. The first principal component exhibited a pattern of finger extension reversing to flexion, whereas the second principal component became important only in the second half of the reaching movement.

Arm↗
PubMed2005

Functional connectivity reveals load dependent neural systems underlying encoding and maintenance in verbal working memory.

One of the main challenges in working memory research has been to understand the degree of separation and overlap between the neural systems involved in encoding and maintenance. In the current study we used a variable load version of the Sternberg item recognition test (two, four, six, or eight letters) and a functional connectivity method based on constrained principal component analysis to extract load-dependent neural systems underlying encoding and maintenance, and to characterize their anatomical overlap and functional interaction. Based on the pattern of functional connectivity, constrained principal component analysis identified a load-dependent encoding system comprising bilateral occipital (Brodmann's area (BA) 17, 18), bilateral superior parietal (BA 7), bilateral dorsolateral prefrontal (BA 46), and dorsal anterior cingulate (BA 24, 32) regions. For maintenance, in contrast, constrained principal component analysis identified a system that was characterized by both load-dependent increases and decreases in activation. The structures in this system jointly activated by maintenance load involved left posterior parietal (BA 40), left inferior prefrontal (BA 44), left premotor and supplementary motor areas (BA 6), and dorsal cingulate regions (BA 24, 32), while the regions displaying maintenance-load-dependent activity decreases involved bilateral occipital (BA 17, 18), posterior cingulate (BA 23) and rostral anterior cingulate/orbitofrontal (BA 10, 11, 32) regions. The correlation between the encoding and maintenance systems was strong and negative (Pearson's r = -.55), indicting that some regions important for visual processing during encoding displayed reduced activity during maintenance, while subvocal rehearsal and phonological storage regions important for maintenance showed a reduction in activity during encoding. In summary, our analyses suggest that separable and complementary subsystems underlie encoding and maintenance in verbal working memory, and they demonstrate how constrained principal component analysis can be employed to characterize neuronal systems and their functional contributions to higher-level cognition.

Adolescent↗
PubMedDate not supplied

Rate code input produces temporal code output from cockroach antennal lobes.

The experiments presented here were designed to determine the origin of the temporally complex activity of antennal lobe projection neurons in the cockroach olfactory system. We determined this through the use of complex chemical stimuli that evoked neural activity recorded extracellularly from olfactory sensory neurons and intracellularly from antennal lobe projection neurons in the cockroach Periplaneta americana. Olfactory information was represented by a simple, short time-scale rate code in the olfactory sensory neurons. This rate code input from the sensory neurons was processed by the antennal lobe and transformed into a longer time-scale, temporally encoded output expressed across a smaller population of antennal lobe projection neurons. The projection neuron responses comprised temporal patterns of increases and decreases in spike frequency that differed among projection neurons and were consistent among repeated presentations of the same stimulus. Presentation of simple and complex chemical stimuli showed that the complexity of projection neuron activity was a product of the antennal lobes and was not associated with the chemical complexity of the stimulus. To characterize the encoding schemes used by each class of neurons, the responses were decomposed into their principal components. The stimulus was correlated with only the first principal component of the activity of sensory neurons, which is consistent with a rate encoding scheme. The stimulus was correlated with higher order principal components of the activity of projection neurons, which is consistent with a temporal encoding scheme.

Action Potentials↗
PubMed2004

Craniometric relationships among medieval Central European populations: implications for Croat migration and expansion.

AIM: To determine the ethnic composition of the early medieval Croats, the location from which they migrated to the east coast of the Adriatic, and to separate early medieval Croats from Bijelo brdo culture members, using principal components analysis and discriminant function analysis of craniometric data from Central and South-East European medieval archaeological sites. METHODS: Mean male values for 8 cranial measurements from 39 European and 5 Iranian sites were analyzed by principal components analysis. Raw data for 17 cranial measurements for 103 female and 112 male skulls were used to develop discriminant functions. RESULTS: The scatter-plot of the analyzed sites on the first 2 principal components showed a pattern of intergroup relationships consistent with geographical and archaeological information not included in the data set. The first 2 principal components separated the sites into 4 distinct clusters: Avaroslav sites west of the Danube, Avaroslav sites east of the Danube, Bijelo brdo sites, and Polish sites. All early medieval Croat sites were located in the cluster of Polish sites. Two discriminant functions successfully differentiated between early medieval Croats and Bijelo brdo members. Overall accuracies were high -- 89.3% for males, and 97.1% for females. CONCLUSION: Early medieval Croats seem to be of Slavic ancestry, and at one time shared a common homeland with medieval Poles. Application of unstandardized discriminant function coefficients to unclassified crania from 18 sites showed an expansion of early medieval Croats into continental Croatia during the 10th to 13th century.

Archaeology↗
PubMed1982

Haematological findings in healthy and diseased rabbits, a multivariate analysis.

Haematological data from 94 diseased rabbits and 23 healthy adult rabbits were analysed statistically using principal components analysis and multiple discriminant function analysis. The 1st principal component accounted for 32% of the variation and was interpreted as showing total blood cellularity. This was decreased in the majority of diseased rabbits, principally due to anaemia, although in a few it was slightly increased possibly as a result of dehydration. The 2nd principal component (22% of the variation) had high positive loadings on monocyte and heterophil counts and weak negative loadings on the red cell characters. This component was interpreted as the response of the white blood cells to disease. When classification analysis was used to decide whether or not an animal was 'normal' the heterophil and lymphocyte counts alone provided almost as accurate an assessment as when all the blood parameters were taken into account. The role of these analyses in the diagnosis of disease is discussed.

Analysis of Variance↗
PubMed1978

Size and shape of Kedah-Kelantan cows.

Body weight and nine body measurements were recorded on 79 mature Kedah-Kelantan cows at two locations. The Kedah-Kelantan is an indigenous cattle of Malaysia. A principal component analysis was used to study size and shape as indicated by the dependence structure among measurements. The total variation among measurements associated with the first principal component which was interpreted as a measure of general size was 40.8%. The second principal component contrasted cows tall at the withers, and deep at the chest with top line sloping downward and under line sloping upward from front to rear with those having less wither height and chest depth and straighter lines. This contrast accounted for 14.3% of the variation in body dimensions. The third principal component contrasted long, narrow, and deeper cows with a more compact type. This contrast accounted for 10.7% of the variation in body dimensions.

Adaptation, Biological↗
PubMed2005

Responses of calves to acute stress: individual consistency and relations between behavioral and physiological measures.

The present study examined the consistency over time of individual differences in behavioral and physiological responsiveness of calves to intuitively alarming test situations as well as the relationships between behavioral and physiological measures. Twenty Holstein Friesian heifer calves were individually subjected to the same series of two behavioral and two hypothalamo-pituitary-adrenocortical (HPA) axis reactivity tests at 3, 13 and 26 weeks of age. Novel environment (open field, OF) and novel object (NO) tests involved measurement of behavioral, plasma cortisol and heart rate responses. Plasma ACTH and/or cortisol response profiles were determined after administration of exogenous CRH and ACTH, respectively, in the HPA axis reactivity tests. Principal component analysis (PCA) was used to condense correlated measures within ages into principal components reflecting independent dimensions underlying the calves' reactivity. Cortisol responses to the OF and NO tests were positively associated with the latency to contact and negatively related to the time spent in contact with the NO. Individual differences in scores of a principal component summarizing this pattern of inter-correlations, as well as differences in separate measures of adrenocortical and behavioral reactivity in the OF and NO tests proved highly consistent over time. The cardiac response to confinement in a start box prior to the OF test was positively associated with the cortisol responses to the OF and NO tests at 26 weeks of age. HPA axis reactivity to ACTH or CRH was unrelated to adrenocortical and behavioral responses to novelty. These findings strongly suggest that the responsiveness of calves was mediated by stable individual characteristics. Correlated adrenocortical and behavioral responses to novelty may reflect underlying fearfulness, defining the individual's susceptibility to the elicitation of fear. Other independent characteristics mediating reactivity may include activity or coping style (related to locomotion) and underlying sociality (associated with vocalization).

Acute Disease↗
PubMed2006

Characterization of surface marine sediments from Ría de Arousa estuary according to extractable humic matter content.

Surface marine sediments from Ría de Arousa estuary were analyzed for humic and fulvic acids by UV-visible spectrometry and have been characterized using elemental analysis (carbon, hydrogen and nitrogen elemental composition) and spectrometric data (A2/A4 ratio, absorbancies at 270 and 407 nm and E4/E6 ratio, absorbancies at 465 and 665 nm). These variables have been used as discriminating factors to distinguish of marine and terrestrial origin of humic and fulvic acids in Ría de Arousa surface marine sediments. Principal component analysis, PCA, and cluster analysis, CA, have been used as unsupervised pattern recognition procedures. The half-range central value transformation was used as data pre-treatment to homogenize data. After a Varimax rotation, PCA applied to humic acid data has reveled that spectrometric A2/A4 and E4/E6 ratios are the main dominating features in the first principal component (48.6% of total variance), the humic acid content is the feature with the highest weight in the second principal component (22.9% of the total variability) and the carbon elemental composition domain in the third principal component (13.3% of total variance). Results from PCA have revealed that surface sediments collected at inner-left part of the estuary and at the mouth of the river Ulla belong to the same group. Similarly, PCA has shown that surface sediments from the right mouth of the estuary form a compact group. Taking in account the water circulation in Ría de Arousa estuary, these findings mean that the organic matter in surface sediments from the inner-left part of the estuary derived mainly from terrestrial organic matter while the organic matter in surface sediments from the right mouth of the estuary is mainly derived from marine sources. Finally, it must be noticed that any classification of surface sediments was assessed when applying of PCA and CA from fulvic acids data.

Carbon↗