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Harmonic analysis and clustering of facial profiles.

The profiles of 83 healthy young adults were traced from right-side photographs, and then digitized with an image analyzer; each profile thus consisted of a series of coordinates. A dedicated computer program using Fourier analysis resulted in an equation of a curve that interpolated all profile points. By means of cluster analysis, profile equations were divided; two clusters each were found for male and female subjects. A mean profile was calculated for each of the clusters, so that four mean profiles were obtained. These profiles were compared with esthetic parameters found in literature; the results showed that the conventional parameters could sometimes give misleading information for orthodontic and craniofacial orthopedic treatment plans.

Adult↗

Expression profiling of 68 glycosyltransferase genes in 27 different human tissues by the systematic multiplex reverse transcription-polymerase chain reaction method revealed clustering of sexually related tissues in hierarchical clustering algorithm analysis.

We have developed an experimental system to study the expression of 68 human glycosyltransferase genes. Using this system, we examined the expression of those genes in 27 different tissues by the technique which we named systematic multiplex reverse transcription-polymerase chain reaction (SM RT-PCR). The panoramic view of a total of 1836 (68 x 27) expression data demonstrates that some glycosyltransferase genes are differentially expressed whereas some others are ubiquitously expressed. The data gathered provide more information on glycosyltransferase gene expression in tissues than any other paper published, and surpass in quantity all the information combined from previous publications. Although the expression profiling of glycosyltransferase genes alone may not directly explain the repertoires of oligosaccharides synthesized, it is an important step toward a better understanding of the gene expression network involved in oligosaccharide synthesis/degradation. Our modestly high-throughput gene expression study and the data analysis using a hierarchical clustering algorithm have allowed us to investigate the correlation between tissues and glycosyltransferase gene expression. Similar patterns of glycosyltransferase gene expression were observed in functionally and anatomically related tissues. All, but one, sexually related tissues formed a cluster in a tissue dendrogram, suggesting the involvement of sex hormones in the transcriptional control of many glycosyltransferase genes. Once established, the SM RT-PCR is cost- and time-efficient and requires small amounts of RNA as template. It is especially useful for the simultaneous analyses of multiple samples. Because of its simple design, the SM RT-PCR may offer an easy alternative in studying the expression of many other families of genes, as well as groups of related/unrelated genes, in various biological phenomena.

Algorithms↗

Clusters of problem behaviors in adolescents.

This study was designed to examine clusters of problem behaviors in a sample from the National Longitudinal Study of Adolescent Health at two time points. The technique employed was a person-oriented approach, cluster analysis. Three clusters were identified, a normal behaviors cluster, a problem behaviors cluster, and a deviant behaviors cluster. The clusters were tested for stability and for their relationships to the demographic variables gender, race, age, and socioeconomic status. The mean values for most of the problem behaviors in the problem behaviors cluster were higher than for those in the normal behaviors cluster and lower than for those in the deviant behaviors cluster. Selling drugs and weapon use distinguished the deviant behaviors cluster from the other two. Different interventions probably will be required to address the needs of those in each of the different clusters.

Adolescent↗

Genomic imbalances in drug-resistant T-cell acute lymphoblastic CEM leukemia cell lines.

Ten T-cell acute lymphoblastic (T-ALL) CEM cell lines selected for resistance toward methotrexate (CEM/MTX60PGA, CEM/MTX140LV, CEM/MTX1500LV, CEM/MTX5000PGA, CEM/MTXR1, CEM/MTXR2, and CEM/MTXR3), doxorubicin (CEM/ADR5000), vincristine (CEM/VCR1000), or hydroxyurea (CEM/HUR90), respectively, and parental drug-sensitive CCRF-CEM cells were analyzed using comparative genomic hybridization. Most genomic imbalances were not specific for drug resistance, as they were found in both parental and drug-resistant lines. Three aberrations were common to all or most cell lines analyzed: dim(5q35), dim(9p21p24), and enh(20q). We were concerned on those imbalances which were specifically present in drug-resistant but not in drug-sensitive cells. All methotrexate-resistant cell lines were characterized by an enhancement or an amplification of 5q13. The methotrexate resistance-conferring dihydrofolate reductase (DHFR) gene is located at this locus. Gain of DHFR was verified by PCR analyses. CEM/MTX60PGA, CEM/MTX140LV, CEM/MTX1500LV, and CEM/MTX5000PGA showed enh(14q21qter) and CEM/MTX5000PGA amp(5p13p15.2). These two loci harbor the methylenetetrahydrofolate dehydrogenase (MTHFD1) and 5'-methyltetrahdrofolate-homocysteine methyltransferase reductase (MTRR) genes, both of which are involved in folate metabolism. Their gain indicates a role in methotrexate resistance. A loss of 4q35 was found in CEM/MTXR2, CEM/MTXR3, and CEM/ADR5000 where the proapoptotic caspase-3 gene is located. The thioredoxin (TXN) locus 9q31 was enhanced in CEM/ADR5000 and CEM/MTX5000PGA cells. 2p22pter was increased in hydroxyurea-resistant CEM/HUR90 cells. Ribonucleotide reductase polypeptide M2 (RRM2), which confers resistance to hydroxyurea, resides at this locus. Other specific genomic imbalances in drug-resistant cell lines were dim(1p36.5), enh(4p), dim(8p22pter), enh(12p13), dim(17p), enh(18q12), enh(21q22.2), dim(21q22.2), and dim(22q13). All genomic imbalances were subjected to hierarchical cluster analysis and clustered image mapping to identify profiles of chromosomal aberrations in the cell lines. The obtained dendrograms allowed separation of imbalances common to all or most cell lines from other more individual aberrations. Furthermore, methotrexate-resistant cell lines clustered together. Our future efforts will be directed toward those imbalances which implicate still unknown candidate drug resistance genes.

Antineoplastic Agents↗

Combination treatment of glioblastoma multiforme cell lines with the anti-malarial artesunate and the epidermal growth factor receptor tyrosine kinase inhibitor OSI-774.

New drugs and combination modalities for otherwise non-responsive brain tumors are urgently required. The anti-malarial artesunate (ART) and the EGFR tyrosine kinase inhibitor OSI-774 reveal profound cytotoxic activity. The effectiveness of a combination treatment and the underlying molecular determinants of cellular response are unknown. In the present investigation, we studied ART and OSI-774 in glioblastoma multiforme (GBM) cell lines. Supra-additive inhibition of cell growth was observed in U-87MG.DeltaEGFR cells transduced with a deletion-mutant constitutively active EGFR gene, while additive effects were present in cells transduced with wild-type EGFR (U-87MG.WT-2N), kinase-deficient EGFR (U-87MG.DK-2N), mock vector controls (U-87MG.LUX), or non-transduced parental U-87MG cells. Among nine other non-transduced GBM cell lines, supra-additive effects were found in two cell lines (G-210GM, G-599GM), while ART and OSI-774 acted in an additive manner in the other seven cell lines (G-211GM, G-750GM, G-1163GM, G-1187GM, G-1265GM, G-1301GM, and G-1408GM). Sub-additive or antagonistic effects were not observed. Genomic gains and losses of genetic material in the non-transduced cell lines as assessed by comparative genomic hybridization were correlated with the IC(50) values for ART and OSI-774 and subsequently subjected to hierarchical cluster analysis and cluster image mapping. A genomic profile of imbalances was detected that predicted cellular response to ART and OSI-774. The genes located at the genomic imbalances of interest may serve as candidate resistance genes of GBM cells towards ART and OSI-774. In conclusion, the combination treatment of ART and OSI-774 resulted in an increased growth inhibition of GBM cell lines as compared to each drug alone.

Antineoplastic Combined Chemotherapy Protocols↗

Chemical characterisation of PM episodes in NE Spain.

The chemical composition of ambient particulate matter (PM) varies widely as a function of its main emission sources and of the chemical reactions which take place in the atmosphere. The aim of this study is to obtain the chemical profile of PM10 and PM2.5 during peak PM episodes, thus identifying the main emission sources and/or atmospheric processes which originate the PM episodes. To this end, cluster analysis was applied to a set of PM10 and PM2.5 data collected throughout 2001 in two urban and industrialised areas in NE Spain. As a result of this analysis, five clusters were identified for each site, and the interpretation of their chemical profiles lead to the identification of five types of peak PM episodes for each site: industrial, traffic and regional re-circulation episodes at both sites, plus crustal episodes in Barcelona, and peak traffic and industrial episodes (T+I) in Tarragona. Traffic episodes are characterised by daily means of 23 and 10 microg/m3 of OM+EC in Barcelona and Tarragona in PM10. Levels of secondary inorganic aerosols reach average daily means of 19 and 11 microg/m3 in Barcelona and Tarragona in PM10 during industrial episodes. High levels of sulphate (>5 microg/m3) and ozone (up to 77 microg/m3 daily mean) are good tracers of regional re-circulation episodes. During crustal episodes daily means of crustal elements reach up to 34 microg/m3 in Barcelona. Special attention has been drawn to the composition of the mineral matter during the different PM episodes.

Air Pollutants↗

Parentage assessment of an IVF calf from Bubalus bubalis by DNA fingerprinting.

We used two synthetic oligodeoxyribonucleotide probes, OAT18 and OMS1 comprising (TGG)6 and (GGTA)4 repeat motifs, respectively, in combination with HinfI enzyme for DNA fingerprinting of a calf born from embryo transfer technology, its surrogate mother (SM) and the sperm donor (bull). Of the two polymorphic probes, OAT18 was found to be more informative for correctly establishing the parentage status of the in-vitro fertilized (IVF) calf and demonstrated the genetic relationship of the SM with the bull. Two types of cluster analysis, SAHN clustering and neighbour joining tree, performed with similarity indices of these individuals produced by OAT18 probe were found to be different. Using the SAHN cluster method, SM was found to be genetically closer to the bull than to IVF calf, whereas using the neighbour joining method, IVF was closer to bull than SM. A similar result was obtained by SAHN clustering with OMS1 probe. The relevance of this approach for parentage control in the context of animal biotechnology is described.

Animals↗

Microarray expression profiles of angiogenesis-related genes predict tumor cell response to artemisinins.

Artemisinin (ARS) and its derivatives are used for the second-line therapy of malaria infections with Plasmodium falciparum and P. vivax. ARSs also reveal profound antitumor activity in vitro and in vivo. In the present investigation, we correlated the mRNA expression data of 89 angiogenesis-related genes obtained by microarray hybridization from the database of the US National Cancer Institute with the 50% growth inhibition concentration values for eight ARSs (ARS, arteether (ARE), artesunate (ART), artemisetene, arteanuine B, dihydroartemisinylester stereoisomers 1 and 2). The constitutive expression of 30 genes correlated significantly with the cellular response to ARSs. By means of hierarchical cluster analysis and cluster image mapping expression, profiles were identified that determined significantly the cellular response to ART, ARE, artemether and dihydroartemisinylester stereoisomer 1. We have exemplarily validated the microarray data of six out of these 30 genes by real-time RT-PCR in seven cell lines. The fact that sensitivity and resistance of tumor cells could be predicted by the mRNA expression of angiogenesis-related genes indicate that ARSs reveal their antitumor effects at least in part by inhibition of tumor angiogenesis. As many chemopreventive drugs exert antiangiogenic features, ARSs might also be chemopreventive in addition to their cytotoxic effects.

Angiogenic Proteins↗

Assessing the effect of a single dose florfenicol treatment in feedlot cattle on the antimicrobial resistance patterns in faecal Escherichia coli.

The objective of this clinical trial was to examine the effect of a single dose of florfenicol on antimicrobial resistance patterns in faecal E. coli of feedlot steers. Steers (n = 370), were purchased from two sources and housed in outdoor concrete floored pens. Two cattle from each pen (n = 42 pens, 84 cattle) were randomly selected for faecal sampling at study day 1, 14, 28, and 42. One sampled animal from each of 21 pens was randomly selected to receive a single 39.6 mg/kg dose of florfenicol subcutaneously at study day 11. Ten lactose positive colonies were isolated from faecal swabs and tested for antimicrobial resistance to 11 antimicrobials using the disk diffusion method. Zones of inhibition were grouped using cluster analysis and clusters were ordered by increasing multiple resistance. A cumulative logistic regression model using generalized estimating equations was used to assess factors associated with increasing levels of multiple resistance. Immediately post-treatment, all isolates obtained from treated cattle belonged to multiple resistant clusters containing chloramphenicol resistance. Though less pronounced in later sampling, resistance to chloramphenicol and other antimicrobials persisted. Antimicrobial treatment, sampling time and animal source, as well as interactions between these variables, were important predictors of the odds of E. coli belonging to a more resistant cluster. A very clear but transitory shift to increasingly multiple resistant faecal E. coli in response to florfenicol treatment was observed. There was no indication of horizontal transfer of resistant E. coli between steers. Level of resistance was influenced by complex interaction of animal source and previous management.

Animals↗

Patterns of urges during early abstinence in alcohol-dependent subjects.

Urges for alcohol can lead to relapse, but some alcoholics report few urges. We hypothesized that ecological momentary assessment techniques would reveal multiple urge patterns in newly-abstinent alcoholics. Forty-eight alcohol-dependent subjects used PDAs to assess urges to drink in abstinence. Mean and standard deviation of urges were used in cluster analysis, and cluster characteristics were compared. Four clusters were defined, the largest cluster including 29 subjects with low mean urge and low variability. Clusters differed in negative affect and anger but not in abstinence rates. Four distinct urge patterns during abstinence were identified, and 60% of abstinent, alcohol-dependent subjects reported low, stable urge levels.

Adult↗

A 50-year longitudinal study of defense use among inner city men: a validation of the DSM-IV defense axis.

The patterns of use of defense mechanisms by 306 inner-city men were rated from interviews at age 47 and these ratings were analyzed by cluster analysis. Five clusters resulted. The correlates of cluster membership were examined using data from the 50-year longitudinal study of these men. One cluster exhibited the greatest use of mature defenses; the men in this cluster functioned best on all psychosocial and health variables. Two clusters of men used primarily neurotic defenses; these men functioned at an intermediate level on all outcomes. The men in two clusters primarily used immature defenses. The men in one of these clusters used primarily action defenses, whereas the men in the other cluster were the greatest users of projection and fantasy. In general, the men in both these clusters functioned worse than those in the other three. However, the users of action defenses exhibited greater sociopathy, alcohol problems, and marital instability. The findings provide general support for the DSM-IV hierarchy for nonpsychotic defenses, with mature defenses at the top, neurotic defenses in the middle, and action defenses toward the bottom. In particular, the study supports the DSM-IV distinction of action defenses from other immature defenses.

Adaptation, Psychological↗

Temporomandibular disorder subtypes according to self-reported physical and psychosocial variables in female patients: a re-evaluation.

Several studies support the relevance of psychological and psychosocial factors in the assessment and management of chronic musculoskeletal pain disorders, including temporomandibular pain disorders (TMDs). The aim of this study was to re-evaluate subtyping approach used in an earlier study (TI Suvinen, KR Hanes, JA Gerschman, PC Reade. J Orofac Pain 1997;11:200) and to compare perceived physical symptoms, psychological, coping and psychosocial variables between subtypes of patients who seek treatment for their temporomandibular pain and dysfunction. A total of 41 consecutive female patients were assessed multiaxially for physical symptoms, coping style and effectiveness and illness behaviour by a previously validated Temporomandibular Pain Dysfunction Questionnaire (TI Suvinen, KR Hanes, JA Gerschman, PC Reade. J Orofac Pain 1997;11:200). Additional measures of psychosocial variables included the global scores of the Beck Depression and Anxiety Inventory and Part I of the Multidimensional Pain Inventory. Subtypes were generated using an iterative partitioning method, k-means cluster analysis. Three clusters were identified and termed as Simple (22%), Intermediate (41%) and Complex (37%) temporomandibular disorders subtypes. Significant differences (P < 0.05) were found between clusters in psychological (coping style and effectiveness, disease conviction and affective disturbance) and in psychosocial variables (daily interference and social, work and family satisfaction), but not between physical variables. The results support previous studies that have shown differences in psychosocial variables in the presentation and subtyping of TMDs and the biopsychosocial orientation in assessment. The findings need to be reverified in a larger sample along specific physical diagnoses, but it is tentatively proposed how the three subtypes could be used in the classification of temporomandibular pain patients to guide management, based on the constellation of predominant psychological and psychosocial illness impact variables.

Adaptation, Psychological↗

Prevalence and cluster typology of maladaptive behaviors in a geographically defined population of adults with learning disabilities.

BACKGROUND: Maladaptive behaviours are frequently present in individuals with learning disabilities; however, their prevalence varies between studies and the aetiology, classification and most appropriate management of such behaviors remain unclear. The aims of the study were twofold: firstly to determine the prevalence of maladaptive behaviours, and secondly to develop a classification typology. METHOD: A population of 2202 adults with learning disabilities was surveyed to determine the prevalence of maladaptive behaviours. These were subjected on the basis of 13 behavioural characteristics to cluster analysis. The clusters were further examined in respect of secondary variables. RESULTS: Over 60% of individuals demonstrated the presence of at least one maladaptive behaviour and in 40% this problem was of either severe degree or frequent occurrence. Men were more likely to demonstrate physical aggression, property destruction, tantrums and verbal abuse than women. Although some severe maladaptive behaviours diminished with age, many persisted through all age groups. Six behavioural clusters were devised which demonstrated face validity and which differed in respect of demographic and developmental variables, and the prevalence of maladaptive habits and autistic symptoms. CONCLUSIONS: These findings demonstrate a high prevalence of maladaptive behaviours and 'objectionable habits' among people with learning disabilities. A classification of behavioural symptoms may be possible on the basis of symptom clusters.

Adolescent↗

[Perception of odor quality by Free Image-Association Test].

A method was devised for evaluating odor quality. Subjects were requested to freely describe the images elicited by smelling odors. This test was named the "Free Image-Association Test (FIT)". The test was applied for 20 flavors of various foods, five odors from the standards of T&T olfactometer (Japanese standard olfactory test), butter of yak milk, and incense from Lamaism temples. The words for expressing imagery were analyzed by multidimensional scaling and cluster analysis. Seven clusters of odors were obtained. The feature of these clusters were quite similar to that of primary odors which have been suggested by previous studies. However, the clustering of odors can not be explained on the basis of the primary-odor theory, but the information processing theory originally proposed by Miller (1956). These results support the usefulness of the Free Image-Association Test for investigating odor perception based on the images associated with odors.

Adult↗

Phytolith assemblages and systematic associations in grassland species of the South-eastern Pampean plains, Argentina.

BACKGROUND AND AIMS: Phytolith descriptions of South American plant species are scarce. This knowledge is crucial for the interpretation of the fossil phytolith record of a region. In this study phytolith assemblages and systematic relationships of the main grasses and Asteraceae species of Paspalum quadrifarium grassland are described. METHODS: Phytoliths from leaves of Poaceae and Asteraceae species were extracted by using a calcination technique. For each species, 350-400 phytoliths were counted and the relative frequency of each morphotype was calculated. Phytolith assemblages were subject to principal components analysis (PCA) and cluster analysis (Morisita index). KEY RESULTS: PCA and cluster analysis showed family (Poaceae vs. Asteraceae) and subfamily (within Poaceae) differentiation. Exceptions to general trends described for other species were detected. Floristic variants of Paspalum quadrifarium grassland can be separated by their phytolith assemblages. CONCLUSIONS: The study provides a reference collection of phytolith assemblages of the main Poaceae and Asteraceae species of Paspalum quadrifarium grassland and describes some phytolith morphotypes/systematic relationships useful for the analysis of fossil phytolith assemblages of the Pampean region.

Argentina↗

Pvclust: an R package for assessing the uncertainty in hierarchical clustering.

SUMMARY: Pvclust is an add-on package for a statistical software R to assess the uncertainty in hierarchical cluster analysis. Pvclust can be used easily for general statistical problems, such as DNA microarray analysis, to perform the bootstrap analysis of clustering, which has been popular in phylogenetic analysis. Pvclust calculates probability values (p-values) for each cluster using bootstrap resampling techniques. Two types of p-values are available: approximately unbiased (AU) p-value and bootstrap probability (BP) value. Multiscale bootstrap resampling is used for the calculation of AU p-value, which has superiority in bias over BP value calculated by the ordinary bootstrap resampling. In addition the computation time can be enormously decreased with parallel computing option.

Algorithms↗

Classification of nonspecific low back pain. II. Clinical diversity of organic forms.

A classification study was conducted in an unselected sample of outpatient subjects with localized nonspecific low back pain. The heterogeneity of a subgroup of patients without a psychiatric disorder according to the DSM-III classification (axis I), and whose low back pain may be labeled as 'purely organic' (see part 1 of the study in the companion paper), led to further evaluation of this group by correspondence and cluster analysis. A seven-cluster population structure emerged from the cluster analysis. Comprehensive description of these clusters suggests at least four well-differentiated clinical entities or 'syndromes.' Although no satisfactory correlation with pre-existing 'pathoanatomic' classification or hypotheses was found, this variable clinical presentation suggests different etiological or physiopathologic patterns for low back pain (and possibly more specific management of this condition). More comprehensive descriptions and evaluations of clinical symptoms and syndromes appear necessary in order to elaborate a clinical classification of LBP.

Acute Disease↗

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↗