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Automatic selection of arterial input function using cluster analysis.

Quantification of cerebral blood flow (CBF) using dynamic susceptibility contrast MRI requires determination of the arterial input function (AIF) representing the delivery of intravascular tracer to tissue. This is typically accomplished manually by inspection of concentration time curves (CTCs) in regions containing the ICA, VA, and MCA. This is, however, a time consuming and operator dependent procedure. We suggest a completely automatic procedure for establishing the AIF based on a cluster analysis algorithm. In 20 normal subjects CBF maps calculated in 2 slices by the automatic procedure were compared to maps obtained with AIFs selected individually by 7 experienced operators. The average manual to automatic CBF ratio was 1.03+/-0.15 in the lower slice and 1.05+/-0.12 in the upper slice, demonstrating excellent agreement between the manual and automatic method. The algorithm provides means for objectively assessing AIF candidates in local AIF search algorithms designed to reduce bias due to delay and dispersion. Given the reproducibility and speed (10 s) of the automatic method, we speculate that it will greatly improve the accuracy of perfusion images and facilitate their use in clinical diagnosis and decision-making, particularly in acute stroke but also in cerebrovascular disease in general.

Aged↗

Cluster analysis of self-awareness levels in adults with traumatic brain injury and relationshipto outcome.

The purpose of this study was to investigate the relationship between self-awareness, emotional distress, motivation, and outcome in adults with severe traumatic brain injury. A sample of 55 patients were selected from 120 consecutive patients with severe traumatic brain injury admitted to the rehabilitation unit of a large metropolitan public hospital. Subjects received multidisciplinary inpatient rehabilitation and different types of outpatient rehabilitation and community-based services according to availability and need. Measures used in the cluster analysis were the Patient Competency Rating Scale, Self-Awareness of Deficits Interview, Head Injury Behavior Scale, Change Assessment Questionnaire, the Beck Depression Inventory, and Beck Anxiety Inventory; outcome measures were the Disability Rating Scale, Community Integration Questionnaire, and Sickness Impact Profile. A three-cluster solution was selected, with groups labeled as high self-awareness (n = 23), low self-awareness (n = 23), and good recovery (n = 8). The high self-awareness cluster had significantly higher levels of self-awareness, motivation, and emotional distress than the low self-awareness cluster but did not differ significantly in outcome. Self-awareness after brain injury is associated with greater motivation to change behavior and higher levels of depression and anxiety; however, it was not clear that this heightened motivation actually led to any improvement in outcome. Rehabilitation timing and approach may need to be tailored to match the individual's level of self-awareness, motivation, and emotional distress.

Adult↗

Cluster analysis of comparative genomic hybridization (CGH) data using self-organizing maps: application to prostate carcinomas.

Comparative genomic hybridization (CGH) is a modern genetic method which enables a genome-wide survey of chromosomal imbalances. For each chromosome region, one obtains the information whether there is a loss or gain of genetic material, or whether there is no change at that region. Usually it is not possible to evaluate all 46 chromosomes of a metaphase, therefore several (up to 20 or more) metaphases are analyzed per individual, and expressed as average. Mostly one does not study one individual alone but groups of 20-30 individuals. Therefore, large amounts of data quickly accumulate which must be put into a logical order. In this paper we present the application of a self-organizing map (Genecluster) as a tool for cluster analysis of data from pT2N0 prostate cancer cases studied by CGH. Self-organizing maps are artificial neural networks with the capability to form clusters on the basis of an unsupervised learning rule, i.e., in our examples it gets the CGH data as only information (no clinical data). We studied a group of 40 recent cases without follow-up, an older group of 20 cases with follow-up, and the data set obtained by pooling both groups. In all groups good clusterings were found in the sense that clinically similar cases were placed into the same clusters on the basis of the genetic information only. The data indicate that losses on chromosome arms 6q, 8p and 13q are all frequent in pT2N0 prostatic cancer, but the loss on 8p has probably the largest prognostic importance.

Carcinoma↗

The bereavement response: a cluster analysis.

BACKGROUND: Literature and clinical experience suggest that some people experience atypical, complicated or pathological bereavement reactions in response to a major loss. METHOD: Three groups of community-based bereaved subjects--spouses (n = 44), adult children (n = 40), and parents (n = 36)--were followed up four times in the 13 months after a loss. A 17-item scale of core bereavement times was developed and used to investigate the intensity of the bereavement response over time. RESULTS: Cluster analysis revealed a pattern of bereavement-related symptoms approximating a syndrome of chronic grief in 11 (9.2%) of the 120 subjects. None of the respondents displayed a pattern consistent with delayed or absent grief. CONCLUSIONS: In a non-clinical community sample of bereaved people, delayed or absent grief is infrequently seen, unlike chronic grief, which is demonstrated in a minority.

Adult↗

Assessment of PTT 119 activity on acute nonlymphoblastic leukemia cells by [3H]-thymidine uptake inhibition and cluster analysis.

PTT 119, a new antineoplastic agent, was demonstrated to have antileukemic activity on murine and human cell lines. In this study we assessed the effect of this drug, at concentrations ranging from 100 ng/ml to 10 micrograms/ml, on fresh human leukemic cells from 12 patients affected by ANLL, evaluating the impairment of DNA synthesis in terms of [3H]-thymidine uptake inhibition. Most leukemic cell populations appeared to be responsive to the drug in a dose-related fashion. By cluster analysis, it was possible to discriminate subsets of samples according to PTT 119 sensitivity, and to investigate cross resistance with cytosine arabinoside and daunorubicin. This preclinical study indicates that PTT 119 may deserve applications in the treatment of acute nonlymphoblastic leukemia patients.

Anemia, Refractory, with Excess of Blasts↗

Hierarchical cluster analysis of environmental pollutants through P450 induction in cultured hepatic cells.

Environmental pollutants are classically associated with increased drug metabolism. Cultures of rat hepatocytes, quail hepatocytes, and human hepatoma (Hep G2) cells were used to study the effects of pesticides on drug-metabolizing enzymes. Membrane integrity and mitochondrial activity were evaluated and induction of ethoxycoumarin-O-deethylase and ethoxyresorufin-O-deethylase activities were measured. Induced P450s were identified by immunoblotting. Pentachlorophenol and lindane appeared as the strongest inducers. On the immunoblots, specific antibodies revealed induced CYP1A1 in fetal rat hepatocytes, CYP2B in quail hepatocytes, and CYP3A7 in Hep G2 cells. Pesticide effects on these different activities in each type of cultured cells were compared by cluster analysis. Results obtained under similar conditions with reference inducers phenobarbital (PB) and benzo[a]anthracene and other environmental pollutants (polychlorobiphenyls) were added to previous data prior to multivariate analysis. The tested products fell into four major groups: a first group with pentachlorophenol, identified as a CYP3A inducer; a second group containing the methylcholanthrene-type inducers that increase CYP1A-related activities; a third class represented by dieldrin, a PB-type inducer; a fourth group including inert compounds or weak inducers. Lindane shares the criteria of the second and third groups and seems to induce both CYP1A and CYP2B activities. The current study results highlight the advantage of using several types of cultured hepatocytes to evaluate the short-term toxicity of environmental pollutants in vitro and constitute a useful model for predicting the potential toxicity of pesticides in humans (Hep G2 cells) and wildlife (fetal quail hepatocytes).

7-Alkoxycoumarin O-Dealkylase↗

Selecting pet dogs on the basis of cluster analysis of breed behavior profiles and gender.

Using a computer-generated data base of rankings of 56 breeds of dogs on 13 behavioral traits, a factor analysis was performed to determine the extent to which a few general underlying behavioral tendencies are manifested in specific characteristics. Three factors, referred to as reactivity, aggression, and trainability, accounted for 81% of the variance in the 13 behavioral traits. Subsequently, a cluster analysis was performed to generate 7 clusters of dog breeds on the basis of similarity in scores for each of the 3 main factors. The clusters reflected to some degree the conventional groupings of dogs into working, sporting, hound, and terrier breeds. A quantitative analysis of the ranking of male dogs vs female dogs for the 13 characteristics revealed that males differed from females on 10 traits. It was concluded that these gender and cluster profiles will allow people to select a breed or gender of dog that is most likely to match the emotional and physical needs of the person who will provide a home for the pet.

Animals↗

Qualitative assessment of IC50 values of inhibitors of the neuronal nicotinic acetylcholine receptor using a single chromatographic experiment and multivariate cluster analysis.

It has been widely demonstrated that affinity chromatography can be used to derive binding affinities, and that these affinities can be correlated to data obtained using standard techniques such as membrane binding, ultrafiltration and equilibrium dialysis. The purpose of this study is to evaluate the use of immobilized nicotinic acetylcholine receptor stationary phase in chromatographic experiments to assess the functional activity of series of noncompetitive inhibitors (NCIs) as reflected in their IC50 values. Chromatographically determined retention values and computer generated molecular descriptors were obtained for 29 compounds and the data were analyzed by cluster analysis. The approach qualitatively ranked the test compounds as efficient NCIs (low IC50 values) or poor NCIs (high IC50 values). The data obtained with the 29 compounds used in this study demonstrate that the experimental approach had been able to place 25 of these compounds in the correct IC(50) clusters. To our knowledge, this is the first relationship established between chromatographic retention and IC50 for membrane-bound receptors. These results suggest that the chromatographic approach may be useful in development of lead drug candidates including the determination of off-target binding.

Chromatography, Affinity↗

Classification of bacterial species from proteomic data using combinatorial approaches incorporating artificial neural networks, cluster analysis and principal components analysis.

MOTIVATION: Robust computer algorithms are required to interpret the vast amounts of proteomic data currently being produced and to generate generalized models which are applicable to 'real world' scenarios. One such scenario is the classification of bacterial species. These vary immensely, some remaining remarkably stable whereas others are extremely labile showing rapid mutation and change. Such variation makes clinical diagnosis difficult and pathogens may be easily misidentified. RESULTS: We applied artificial neural networks (Neuroshell 2) in parallel with cluster analysis and principal components analysis to surface enhanced laser desorption/ionization (SELDI)-TOF mass spectrometry data with the aim of accurately identifying the bacterium Neisseria meningitidis from species within this genus and other closely related taxa. A subset of ions were identified that allowed for the consistent identification of species, classifying >97% of a separate validation subset of samples into their respective groups. AVAILABILITY: Neuroshell 2 is commercially available from Ward Systems.

Algorithms↗

Empirically derived eating patterns using factor or cluster analysis: a review.

This paper reviews studies performed to date that have employed cluster or factor analysis to empirically derive eating patterns. Since 1980, at least 93 studies were published that used cluster or factor analysis to define dietary exposures, of which 65 were used to test hypotheses or examine associations between patterns and disease outcomes or biomarkers. Studies were conducted in diverse populations across many countries and continents and suggest that patterns are associated with many different biomarkers and disease outcomes, whether measured by cluster or factor analysis. Despite clear differences in approaches and interpretations, there is some evidence that underlying eating patterns are revealed by either method. Although the research considered herein has created a meaningful body of literature, refining both the factor and cluster analysis methods will help to further establish eating patterns as a sound dietary assessment method.

Cluster Analysis↗

Clustering analysis and pattern discrimination of EMG linear envelopes.

A technique has been developed for performing pattern analysis of EMG activities generated during locomotion. In this development it was found that the shapes of the EMG linear envelopes (LE) are mainly determined by their phase spectra; their magnitude spectra are much less important. Autoregressive (AR) parametric models and discrete Fourier transform (DFT) approaches were tested and compared. The latter was proved to be a better way to describe the EMG LE's. Feature extraction and clustering were performed by doing DFT of EMG LE's, extracting part of the phase and magnitude spectra (in less important degree) as features, and using the percent powers to weigh the corresponding harmonics. The approach was applied to the clustering analysis of EMG LE's of normal and anterior cruciate ligament (ACL) injured subjects during walking.

Anterior Cruciate Ligament Injuries↗

[Subgroups of torticollis spasmodicus from the psychosomatic viewpoint. Results of a cluster analysis of 144 cases. German Study Group of Dystonia Research].

The question of subgroups in idiopathic spasmodic torticollis, which has been discussed in earlier studies in order to define etiologically heterogeneous patient populations has lost some of its relevance since with the injection of botulinum toxin an effective treatment is available. However, psychosocial distress is linked with spasmodic torticollis in a substantial number of patients. In order to define criteria for psychosocial interventions in addition to the treatment with botulinum toxin, a cluster analysis was carried out to identify high-risk populations in terms of psychological and social distress. Five subgroups were defined on the basis of eight variables. Two of these five groups, one group with rotational torticollis and one with laterocollis, emerged as particularly distressed by their physical complaints, the effects of their illness on various areas of life and in terms of psychological functioning. The consistency of the subgroups was tested and statistically confirmed by analysis of variance. In a cross-validation 83.02% of the ungrouped cases were predicted correctly. The authors suggest that the evaluation of psychological and social aspects of the condition should be part of the neurological assessment in order to offer appropriate support to patients, who reveal a high degree of psychological distress.

Adaptation, Psychological↗

Hydrophobic cluster analysis of G protein-coupled receptors: a powerful tool to derive structural and functional information from 2D-representation of protein sequences.

Current methods for comparative analyses of protein sequences are 1D-alignments of amino acid sequences based on the maximization of amino acid identity (homology) and the prediction of secondary structure elements. This method has a major drawback once the amino acid identity drops below 20-25%, since maximization of a homology score does not take into account any structural information. A new technique called Hydrophobic Cluster Analysis (HCA) has been developed by Lemesle-Varloot et al. (Biochimie 72, 555-574), 1990). This consists of comparing several sequences simultaneously and combining homology detection with secondary structure analysis. HCA is primarily based on the detection and comparison of structural segments constituting the hydrophobic core of globular protein domains, with or without transmembrane domains. We have applied HCA to the analysis of different families of G-protein coupled receptors, such as catecholamine receptors as well as peptide hormone receptors. Utilizing HCA the thrombin receptor, a new and as yet unique member of the family of G-protein coupled receptors, can be clearly classified as being closely related to the family of neuropeptide receptors rather than to the catecholamine receptors for which the shape of the hydrophobic clusters and the length of their third cytoplasmic loop are very different. Furthermore, the potential of HCA to predict relationships between new putative and already characterized members of this family of receptors will be presented.

Amino Acid Sequence↗

Assessment of anaesthetic depth by clustering analysis and autoregressive modelling of electroencephalograms.

The brain activity electroencephalogram (EEG) was recorded from 30 healthy women scheduled for hysterectomy. The patients were anaesthetized with isoflurane, halothane or etomidate/fentanyl. A multiparametric method was used for extraction of amplitude and frequency information from the EEG. The method applied autoregressive modelling of the signal, segmented in 2 s fixed intervals. The features from the EEG segments were used for learning and for classification. The learning process was unsupervised and hierarchical clustering analysis was used to construct a learning set of EEG amplitude-frequency patterns for each of the three anaesthetic drugs. These EEG patterns were assigned to a colour code corresponding to similar clinical states. A common learning set could be used for all patients anaesthetized with the same drug. The classification process could be performed on-line and the results were displayed in a class probability histogram. This histogram reflected in all patients the depth of anaesthesia, when the concentration of the anaesthetic agent was adjusted either based on clinical signs or according to the protocol. This uniform display, where colours in a class probability histogram indicate the depth of anaesthesia, may in the future serve as on-line advice for the administration of anaesthetics. A comparison of multiparametric with single parametric methods, based on calculation of median, spectral edge and peak frequencies, questions the reliability of the single parametric methods in monitoring anaesthetic depth.

Adult↗

Application of stepwise cluster analysis in medical research.

A stepwise clustering algorithm, a method of multivariate statistical analysis, is suggested in this paper. The algorithm is designed for solving problems connected with stepwise regression. It is efficient not only in handling both continuous and discrete variables, but also in the nonlinear relationships between the variables. The above procedure was used in an attempt to find out the causal association of esophageal cancer with its precursors, i.e. nitrates and nitrites of nitrosamines, some of which are known to be carcinogenic. An analysis has been made of the correlation between esophageal cancer as well as severe epithelial hyperplasia of the esophagus and the concentrations of NO3- and NO2- in the drinking water. The samples used were collected from 495 wells in 49 production brigades of the Yaocun Commune in Linxian County, Honan Province. The result indicates that esophageal cancer is definitely connected with the levels of NO3- (summer) and NO2- (spring) in the drinking water. Severe epithelial hyperplasia is defintely connected with the contents of NO2- and NO3- in the drinking water collected in spring, autumn and winter. Our preliminary analysis shows that the stepwise clustering algorithm is a useful statistical method to be used for medical research.

Humans↗

A cluster analysis of the effects of storage mites as allergens in relation to certain occupations and living conditions.

The method of cluster analysis was used to examine the data of Wraith, Cunnington & Seymour (1979) to assess the role and allergenic importance of storage mites in house dust and other environments in relation to certain factors thought to influence patients' exposure to these species. The analysis provided strong statistical evidence that (a) excessively damp housing and (b) occupational risks of exposure were the two main factors associated with allergy to these species. It also indicated that sensitivity to D. pteronyssinus remained unaltered in environmental conditions more favourable to the growth and development of storage mites. Furthermore, it was shown that the storage species form a group of similar allergens distinct from the house-dust mite.

Allergens↗

Hydrophobic cluster analysis: an efficient new way to compare and analyse amino acid sequences.

A new method for comparing and aligning protein sequences is described. This method, hydrophobic cluster analysis (HCA), relies upon a two-dimensional (2D) representation of the sequences. Hydrophobic clusters are determined in this 2D pattern and then used for the sequence comparisons. The method does not require powerful computer resources and can deal with distantly related proteins, even if no 3D data are available. This is illustrated in the present report by a comparison of human haemoglobin with leghaemoglobin, a comparison of the two domains of liver rhodanese (thiosulphate sulphurtransferase) and a comparison of plastocyanin and azurin.

Amino Acid Sequence↗

Measures of clinical severity, quality of life, and psychological distress in patients with psoriasis: a cluster analysis.

The impact of psoriasis on patients' quality of life may be quite destructive, and measures of disease status alone seem to have questionable validity in describing the true burden of illness. Our aim was to study, in patients with psoriasis, the relationship between classical measures of clinical status (i.e., PASI and SAPASI) and quality-of-life indexes (i.e., Skindex-29, Dermatology Life Quality Index, Psoriasis Disability Index, Impact of Psoriasis Questionnaire). In addition, two psychological distress indexes (i.e., Psoriasis Life Stress Inventory, 12-item General Health Questionnaire) were assessed. Data were collected between February 2000 and July 2001 at the inpatient wards of the Dermatological Institute IDI-IRCCS, Rome, Italy, in the framework of a large project on clinical, epidemiologic, emotional, and quality-of-life aspects of psoriasis. A cluster analysis of all the above-mentioned instruments was conducted on 786 eligible patients hospitalized with a diagnosis of psoriasis. Correlations between instruments were also analyzed in subsets of patients based on the main variables of interest. The instruments clustered in two distinct groups, one formed by clinical severity measurements and the other grouping all the quality-of-life and psychological indexes. The correlations between instruments observed in the subgroups determined by different sociodemographic and clinical variables showed the same pattern. In conclusion, the dissimilarity between clinical severity assessment and patient-centered measures stresses the need for a more comprehensive assessment of severity of psoriasis.

Adult↗