BACKGROUND: Patients with bipolar disorder (BD) and major depressive disorder (MDD) exhibit depressive episodes with similar symptoms despite having different and poorly understood underlying neurobiology, often leading to misdiagnosis and improper treatment. This exploratory study examined whole-brain functional connectivity (FC) using FC multivariate pattern analysis (fc-MVPA) to identify the FC patterns with the greatest ability to distinguish between currently depressed patients with BD type I (BD I) and those with MDD. METHODOLOGY: In a cross-sectional design, 41 BD I, 40 MDD patients and 63 control participants completed resting state functional magnetic resonance imaging scans. Data-driven fc-MVPA, as implemented in the CONN toolbox, was used to identify clusters with differential FC patterns between BD patients and MDD patients. The identified cluster was used as a seed in a post hoc seed-based analysis (SBA) to reveal associated connectivity patterns, followed by a secondary ROI-to-ROI analysis to characterize differences in connectivity between these patterns among BD I patients, MDD patients and controls. RESULTS: FC-MVPA identified one cluster located in the right frontal pole (RFP). The subsequent SBA revealed greater FC between the RFP and posterior cingulate cortex (PCC) and between the RFP and the left inferior/middle temporal gyrus (LI/MTG) and lower FC between the RFP and the left precentral gyrus (LPCG), left lingual gyrus/occipital cortex (LLG/OCC) and right occipital cortex (ROCC) in MDD patients than in BD patients. Compared with the controls, ROI-to-ROI analysis revealed lower FC between the RFP and the PCC and greater FC between the RFP and the LPCG, LLG/OCC and ROCC in BD patients; in MDD patients, the analysis revealed lower FC between the RFP and the LLG/OCC and ROCC and greater FC between the RFP and the LI/MTG. CONCLUSIONS: Differences in the RFP FC patterns between currently depressed patients with BD and those with MDD suggest potential neuroimaging markers that should be further examined. Specifically, BD patients exhibit increased FC between the RFP and the motor and visual networks, which is associated with psychomotor symptoms and heightened compensatory frontoparietal FC to counter distractibility. In contrast, MDD patients exhibit increased FC between the RFP and the default mode network, corresponding to sustained self-focus and rumination.

• MeSH
• Bipolar Disorder * physiopathology   diagnostic imaging   MeSH
• Depressive Disorder, Major * physiopathology   diagnostic imaging   MeSH
• Adult MeSH
• Connectome methods   MeSH
• Middle Aged MeSH
• Humans MeSH
• Magnetic Resonance Imaging * methods   MeSH
• Brain Mapping methods   MeSH
• Brain physiopathology   diagnostic imaging   MeSH
• Multivariate Analysis MeSH
• Nerve Net diagnostic imaging   physiopathology   MeSH
• Neural Pathways physiopathology   diagnostic imaging   MeSH
• Cross-Sectional Studies MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

A test-statistic typically employed in the gene set enrichment analysis (GSEA) prevents this method from being genuinely multivariate. In particular, this statistic is insensitive to changes in the correlation structure of the gene sets of interest. The present paper considers the utility of an alternative test-statistic in designing the confirmatory component of the GSEA. This statistic is based on a pertinent distance between joint distributions of expression levels of genes included in the set of interest. The null distribution of the proposed test-statistic, known as the multivariate N-statistic, is obtained by permuting group labels. Our simulation studies and analysis of biological data confirm the conjecture that the N-statistic is a much better choice for multivariate significance testing within the framework of the GSEA. We also discuss some other aspects of the GSEA paradigm and suggest new avenues for future research.

• MeSH
• Phenotype MeSH
• Financing, Organized MeSH
• Models, Genetic MeSH
• Multivariate Analysis MeSH
• Oligonucleotide Array Sequence Analysis statistics & numerical data   MeSH
• Gene Expression Profiling statistics & numerical data   MeSH
• Computational Biology MeSH

• MeSH
• Biometry MeSH
• Statistics as Topic MeSH

• Conspectus
• Statistika
• NML Fields
• statistika, zdravotnická statistika
• management, organizace a řízení zdravotnictví

Based on X-ray measurements of the head of 187 adult men with cleft lip and/or palate, the authors compared, using the multivariate method, deviations in the craniofacial morphology between different types of clefts in the following seven groups: cleft lip alone, complete and incomplete isolated cleft palate, cleft of the soft palate only, unilateral complete and incomplete and bilateral complete cleft lip and palate. The X-ray films were evaluated ac- cording to Jarabak’s method. A special position is held by cleft lip alone with minimal skeletal and dental effects. Isolated clefts of the palate display in skeletal analysis the same basic deviations as clefts of the lip and palate; in dental analysis the devia- tions are smaller (in particular there is no retroinclination of the upper incisors). The effect is much milder in iso- lated clefts of the soft palate. In cleft lip and palate there is, in contrast to isolated clefts of the palate, retrusion of the mandible; in bilateral clefts, in conjunction with persisting protrusion of the premaxilla the depth of the upper jaw is not reduced, the facial skeleton is not flattened and the sagittal intermaxillary relations are not impaired. In the basic developmental pattern there is, however, no difference between different types of clefts which affect the palate (probably in conjunction with postoperative sequelae). The variable which differentiates most types of clefts in the skeletal analysis is the depth of the maxilla; in the dental analysis it is the interincisal angle, which is, how- ever, influenced by treatment. Jarabak’s analysis can record the basic deviations of the configuration of the bony face with a cleft but does not detect some important characteristics such as the vertical proportionality of the face and the posteroposition of the maxilla. The assessment of the soft profile is, however, inadequate and unsuitable.

• MeSH
• Adult MeSH
• Cephalometry methods   statistics & numerical data   MeSH
• Skull anatomy & histology   MeSH
• Humans MeSH
• Multivariate Analysis MeSH
• Cleft Palate pathology   MeSH
• Cleft Lip pathology   MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Publication type
• Comparative Study MeSH

For a comprehensive overview of the genetic alterations of neuroblastoma, their association and clinical significance, we conducted a whole-genome DNA copy number analysis. PATIENTS AND METHODS: A series of 493 neuroblastoma (NB) samples was investigated by array-based comparative genomic hybridization in two consecutive steps (224, then 269 patients). RESULTS: Genomic analysis identified several types of profiles. Tumors presenting exclusively whole-chromosome copy number variations were associated with excellent survival. No disease-related death was observed in this group. In contrast, tumors with any type of segmental chromosome alterations characterized patients with a high risk of relapse. Patients with both numerical and segmental abnormalities clearly shared the higher risk of relapse of segmental-only patients. In a multivariate analysis, taking into account the genomic profile, but also previously described individual genetic and clinical markers with prognostic significance, the presence of segmental alterations with (HR, 7.3; 95% CI, 3.7 to 14.5; P < .001) or without MYCN amplification (HR, 4.5; 95% CI, 2.4 to 8.4; P < .001) was the strongest predictor of relapse; the other significant variables were age older than 18 months (HR, 1.8; 95% CI, 1.2 to 2.8; P = .004) and stage 4 (HR, 1.8; 95% CI, 1.2 to 2.7; P = .005). Finally, within tumors showing segmental alterations, stage 4, age, MYCN amplification, 1p and 11q deletions, and 1q gain were independent predictors of decreased overall survival. CONCLUSION: The analysis of the overall genomic pattern, which probably unravels particular genomic instability mechanisms rather than the analysis of individual markers, is essential to predict relapse in NB patients. It adds critical prognostic information to conventional markers and should be included in future treatment stratification.

• MeSH
• Gene Amplification MeSH
• Survival Analysis MeSH
• DNA, Neoplasm genetics   MeSH
• Financing, Organized MeSH
• Genes, myc MeSH
• Infant MeSH
• Humans MeSH
• Multivariate Analysis MeSH
• Biomarkers, Tumor MeSH
• Follow-Up Studies MeSH
• Genomic Instability MeSH
• Neuroblastoma genetics   pathology   MeSH
• Prognosis MeSH
• Proportional Hazards Models MeSH
• Oligonucleotide Array Sequence Analysis MeSH
• Comparative Genomic Hybridization MeSH
• Check Tag
• Infant MeSH
• Humans MeSH
• Publication type
• Multicenter Study MeSH
• Comparative Study MeSH

Natural resistance to Mycobacterium bovis bacillus Calmette-Guerin (BCG) is determined by the Bcg gene (Nramp1), which is exclusively expressed by mature macrophages. The Nramp1 gene is a dominant autosomal gene that has two allelic forms; r confers resistance and s confers susceptibility to infection with intracellular pathogen. Although the wide range of pleiotropic immunological effects of the Nramp1 gene has been described, the exact mechanism of its action remains elusive. In this study we searched for differentially expressed proteins that might provide clues in the studies on Nramp1 gene function. We performed two-dimensional gel electrophoresis of cellular proteins prepared from a B10R macrophage line derived from mice carrying the r allele of the Nramp1 gene, B10S macrophages carrying the s allele, and B10R-Rb macrophages transfected with Nramp1-ribozyme. The classification of protein patterns and selection of distinct proteins characteristic of r or s allele-carrying macrophages was performed using the principal component analysis. We found differential expression of four proteins with the following isoelectric point/molecular weight (pI/Mr) in B10R macrophages compared to B10S and B10R-Rb macrophages: 6.6/25, 7.0/22, 9.1/31.5, and 5.3/8.5. The protein 7.0/22 has been identified as Mn-superoxide dismutase and the best candidate for protein p6.6/25 seems to be Bcl-2 according to the immunoblot analysis. When the splenic macrophages carrying the r or s allele were analyzed, the changes in relative abundance for proteins 6.6/25 and p7.0/22 were satisfactorily reproduced. Overall, the two identified proteins are important in the regulation of intracellular redox balance and the regulation of apoptosis in macrophages, respectively. Our findings may suggest their possible biological role in the innate immunity against intracellular pathogens.

• MeSH
• Electrophoresis, Gel, Two-Dimensional * MeSH
• Cell Line MeSH
• Macrophages * metabolism   MeSH
• Membrane Proteins * genetics   MeSH
• Multivariate Analysis MeSH
• Mycobacterium bovis * immunology   MeSH
• Mice MeSH
• Immunity, Innate MeSH
• Cation Transport Proteins * MeSH
• Carrier Proteins * genetics   MeSH
• Tuberculosis MeSH
• Animals MeSH
• Check Tag
• Mice MeSH
• Animals MeSH
• Publication type
• Research Support, Non-U.S. Gov't MeSH

To compare the predictive ability of primary and secondary Gleason pattern for positive surgical margins in patients with clinically localized prostate cancer and a preoperative Gleason score ≤6. A retrospective analysis of the medical records of patients undergone a radical prostatectomy between January 2005 and October 2010 was conducted. Patients' age, prostate volume, preoperative PSA, biopsy Gleason score, the 1st and 2nd Gleason pattern were entered a univariate and multivariate analysis. The 1st and 2nd pattern were tested for their ability to predict positive surgical margins using receiver operating characteristic curves. Positive surgical margins were noticed in 56 cases (38.1%) out of 147 studied patients. The 2nd pattern was significantly greater in those with positive surgical margins while the 1st pattern was not significantly different between the 2 groups of patients. ROC analysis revealed that area under the curve was 0.53 (p=0.538) for the 1st pattern and 0.60 (p=0.048) for the 2nd pattern. Concerning the cases with PSA <10 ng/ml, it was also found that only the 2nd pattern had a predictive ability (p=0.050). When multiple logistic regression analysis was conducted it was found that the 2nd pattern was the only independent predictor. The second Gleason pattern was found to be of higher value than the 1st one for the prediction of positive surgical margins in patients with preoperative Gleason score ≤6 and this should be considered especially when a neurovascular bundle sparing radical prostatectomy is planned, in order not to harm the oncological outcome.

• MeSH
• Humans MeSH
• Prostatic Neoplasms surgery   pathology   MeSH
• Predictive Value of Tests MeSH
• Prostatectomy MeSH
• Prostate-Specific Antigen blood   MeSH
• Aged MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Aged MeSH
• Publication type
• Comparative Study MeSH

• Keywords
• Analýza dat, Analýza statistická, Regrese,

• Conspectus
• Statistika
• NML Fields
• statistika, zdravotnická statistika

Multivariate techniques better fit the anatomy of complex neuropsychiatric disorders which are characterized not by alterations in a single region, but rather by variations across distributed brain networks. Here, we used principal component analysis (PCA) to identify patterns of covariance across brain regions and relate them to clinical and demographic variables in a large generalizable dataset of individuals with bipolar disorders and controls. We then compared performance of PCA and clustering on identical sample to identify which methodology was better in capturing links between brain and clinical measures. Using data from the ENIGMA-BD working group, we investigated T1-weighted structural MRI data from 2436 participants with BD and healthy controls, and applied PCA to cortical thickness and surface area measures. We then studied the association of principal components with clinical and demographic variables using mixed regression models. We compared the PCA model with our prior clustering analyses of the same data and also tested it in a replication sample of 327 participants with BD or schizophrenia and healthy controls. The first principal component, which indexed a greater cortical thickness across all 68 cortical regions, was negatively associated with BD, BMI, antipsychotic medications, and age and was positively associated with Li treatment. PCA demonstrated superior goodness of fit to clustering when predicting diagnosis and BMI. Moreover, applying the PCA model to the replication sample yielded significant differences in cortical thickness between healthy controls and individuals with BD or schizophrenia. Cortical thickness in the same widespread regional network as determined by PCA was negatively associated with different clinical and demographic variables, including diagnosis, age, BMI, and treatment with antipsychotic medications or lithium. PCA outperformed clustering and provided an easy-to-use and interpret method to study multivariate associations between brain structure and system-level variables. PRACTITIONER POINTS: In this study of 2770 Individuals, we confirmed that cortical thickness in widespread regional networks as determined by principal component analysis (PCA) was negatively associated with relevant clinical and demographic variables, including diagnosis, age, BMI, and treatment with antipsychotic medications or lithium. Significant associations of many different system-level variables with the same brain network suggest a lack of one-to-one mapping of individual clinical and demographic factors to specific patterns of brain changes. PCA outperformed clustering analysis in the same data set when predicting group or BMI, providing a superior method for studying multivariate associations between brain structure and system-level variables.

• MeSH
• Principal Component Analysis * MeSH
• Bipolar Disorder * diagnostic imaging   drug therapy   pathology   MeSH
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Magnetic Resonance Imaging * methods   MeSH
• Young Adult MeSH
• Brain diagnostic imaging   pathology   MeSH
• Cerebral Cortex diagnostic imaging   pathology   MeSH
• Obesity * diagnostic imaging   MeSH
• Schizophrenia diagnostic imaging   pathology   drug therapy   physiopathology   MeSH
• Cluster Analysis MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Young Adult MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

Effects of gender on grey matter (GM) volume differences in subcortical structures of the human brain have consistently been reported. Recent research evidence suggests that both gender and brain size influences volume distribution in subcortical areas independently. The goal of this study was to determine the effects of the interplay between brain size, gender and age contributing to volume differences of subcortical GM in the human brain. High-resolution T1-weighted images were acquired from 53 healthy males and 50 age-matched healthy females. Total GM volume was determined using voxel-based morphometry. We used model-based subcortical segmentation analysis to measure the volume of subcortical nuclei. Main effects of gender, brain volume and aging on subcortical structures were examined using multivariate analysis of variance. No significant difference was found in total brain volume between the two genders after correcting for total intracranial volume. Our analysis revealed significantly larger hippocampus volume for females. Additionally, GM volumes of the caudate nucleus, putamen and thalamus displayed a significant age-related decrease in males as compared to females. In contrast to this only the thalamic volume loss proved significant for females. Strikingly, GM volume decreases faster in males than in females emphasizing the interplay between aging and gender on subcortical structures. These findings might have important implications for the interpretation of the effects of unalterable factors (i.e. gender and age) in cross-sectional structural MRI studies. Furthermore, the volume distribution and changes of subcortical structures have been consistently related to several neuropsychiatric disorders (e.g. Parkinson's disease, attention deficit hyperactivity disorder, etc.). Understanding these changes might yield further insight in the course and prognosis of these disorders.

• MeSH
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Young Adult MeSH
• Brain diagnostic imaging   physiology   MeSH
• Multivariate Analysis MeSH
• Image Processing, Computer-Assisted MeSH
• Sex Characteristics * MeSH
• Pattern Recognition, Automated MeSH
• Gray Matter diagnostic imaging   physiology   MeSH
• Aging pathology   physiology   MeSH
• Organ Size MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Young Adult MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Comparative Study MeSH