Increased Expression of Cell-Cell Signaling Genes by Stimulated Mononuclear Leukocytes in Patients with Previous Atherothrombotic Stroke A Whole Genome Expression Profile Study

Background/Aims: Inflammation plays an important role in atherosclerosis and stroke. Acute infections are recognized as trigger factors for ischemic stroke. Methods: In this whole genome expression profile study of 15 patients and 15 control subjects, we tested the hypothesis that patients with a history of atherothrombotic stroke show enhanced transcription of inflammatory genes in circulating leukocytes. RNA from unstimulated or lipopolysaccharide (LPS)-stimulated peripheral blood mononuclear cells (PBMCs) was analyzed with Affymetrix U133A GeneChips using a pooling design. Expression of single genes and functional groups of genes was analyzed by global statistical tests. Results: A total of 10,197 probe sets showed positive calls. After correction for multiple testing no single probe set revealed significant differences either without or with LPS stimulation. However, significant global expression differences were found upon LPS stimulation for the group of genes that are involved in cell-cell signaling. Conclusion: LPS stimulation of PBMCs, a condition mimicking bacterial infection, induces differential expression of a group of cell-cell signaling genes in patients with previous atherothrombotic stroke. This finding can be caused by genetic differences between both groups, but acquired risk factors, medication and technical factors may also have contributed to the result. Copyright (C) 2009 S. Karger AG, Base

Evaluating automated longitudinal tumor measurements for glioblastoma response assessment.

Automated tumor segmentation tools for glioblastoma show promising performance. To apply these tools for automated response assessment, longitudinal segmentation, and tumor measurement, consistency is critical. This study aimed to determine whether BraTumIA and HD-GLIO are suited for this task. We evaluated two segmentation tools with respect to automated response assessment on the single-center retrospective LUMIERE dataset with 80 patients and a total of 502 post-operative time points. Volumetry and automated bi-dimensional measurements were compared with expert measurements following the Response Assessment in Neuro-Oncology (RANO) guidelines. The longitudinal trend agreement between the expert and methods was evaluated, and the RANO progression thresholds were tested against the expert-derived time-to-progression (TTP). The TTP and overall survival (OS) correlation was used to check the progression thresholds. We evaluated the automated detection and influence of non-measurable lesions. The tumor volume trend agreement calculated between segmentation volumes and the expert bi-dimensional measurements was high (HD-GLIO: 81.1%, BraTumIA: 79.7%). BraTumIA achieved the closest match to the expert TTP using the recommended RANO progression threshold. HD-GLIO-derived tumor volumes reached the highest correlation between TTP and OS (0.55). Both tools failed at an accurate lesion count across time. Manual false-positive removal and restricting to a maximum number of measurable lesions had no beneficial effect. Expert supervision and manual corrections are still necessary when applying the tested automated segmentation tools for automated response assessment. The longitudinal consistency of current segmentation tools needs further improvement. Validation of volumetric and bi-dimensional progression thresholds with multi-center studies is required to move toward volumetry-based response assessment

A global analysis of Y-chromosomal haplotype diversity for 23 STR loci

In a worldwide collaborative effort, 19,630 Y-chromosomes were sampled from 129 different populations in 51 countries. These chromosomes were typed for 23 short-tandem repeat (STR) loci (DYS19, DYS389I, DYS389II, DYS390, DYS391, DYS392, DYS393, DYS385ab, DYS437, DYS438, DYS439, DYS448, DYS456, DYS458, DYS635, GATAH4, DYS481, DYS533, DYS549, DYS570, DYS576, and DYS643) and using the PowerPlex Y23 System (PPY23, Promega Corporation, Madison, WI). Locus-specific allelic spectra of these markers were determined and a consistently high level of allelic diversity was observed. A considerable number of null, duplicate and off-ladder alleles were revealed. Standard single-locus and haplotype-based parameters were calculated and compared between subsets of Y-STR markers established for forensic casework. The PPY23 marker set provides substantially stronger discriminatory power than other available kits but at the same time reveals the same general patterns of population structure as other marker sets. A strong correlation was observed between the number of Y-STRs included in a marker set and some of the forensic parameters under study. Interestingly a weak but consistent trend toward smaller genetic distances resulting from larger numbers of markers became apparent.Peer reviewe

Clinical Evaluation of a Fully-automatic Segmentation Method for Longitudinal Brain Tumor Volumetry.

Information about the size of a tumor and its temporal evolution is needed for diagnosis as well as treatment of brain tumor patients. The aim of the study was to investigate the potential of a fully-automatic segmentation method, called BraTumIA, for longitudinal brain tumor volumetry by comparing the automatically estimated volumes with ground truth data acquired via manual segmentation. Longitudinal Magnetic Resonance (MR) Imaging data of 14 patients with newly diagnosed glioblastoma encompassing 64 MR acquisitions, ranging from preoperative up to 12 month follow-up images, was analysed. Manual segmentation was performed by two human raters. Strong correlations (R = 0.83-0.96, p < 0.001) were observed between volumetric estimates of BraTumIA and of each of the human raters for the contrast-enhancing (CET) and non-enhancing T2-hyperintense tumor compartments (NCE-T2). A quantitative analysis of the inter-rater disagreement showed that the disagreement between BraTumIA and each of the human raters was comparable to the disagreement between the human raters. In summary, BraTumIA generated volumetric trend curves of contrast-enhancing and non-enhancing T2-hyperintense tumor compartments comparable to estimates of human raters. These findings suggest the potential of automated longitudinal tumor segmentation to substitute manual volumetric follow-up of contrast-enhancing and non-enhancing T2-hyperintense tumor compartments

Automatic estimation of extent of resection and residual tumor volume of patients with glioblastoma.

OBJECTIVE In the treatment of glioblastoma, residual tumor burden is the only prognostic factor that can be actively influenced by therapy. Therefore, an accurate, reproducible, and objective measurement of residual tumor burden is necessary. This study aimed to evaluate the use of a fully automatic segmentation method-brain tumor image analysis (BraTumIA)-for estimating the extent of resection (EOR) and residual tumor volume (RTV) of contrast-enhancing tumor after surgery. METHODS The imaging data of 19 patients who underwent primary resection of histologically confirmed supratentorial glioblastoma were retrospectively reviewed. Contrast-enhancing tumors apparent on structural preoperative and immediate postoperative MR imaging in this patient cohort were segmented by 4 different raters and the automatic segmentation BraTumIA software. The manual and automatic results were quantitatively compared. RESULTS First, the interrater variabilities in the estimates of EOR and RTV were assessed for all human raters. Interrater agreement in terms of the coefficient of concordance (W) was higher for RTV (W = 0.812; p < 0.001) than for EOR (W = 0.775; p < 0.001). Second, the volumetric estimates of BraTumIA for all 19 patients were compared with the estimates of the human raters, which showed that for both EOR (W = 0.713; p < 0.001) and RTV (W = 0.693; p < 0.001) the estimates of BraTumIA were generally located close to or between the estimates of the human raters. No statistically significant differences were detected between the manual and automatic estimates. BraTumIA showed a tendency to overestimate contrast-enhancing tumors, leading to moderate agreement with expert raters with respect to the literature-based, survival-relevant threshold values for EOR. CONCLUSIONS BraTumIA can generate volumetric estimates of EOR and RTV, in a fully automatic fashion, which are comparable to the estimates of human experts. However, automated analysis showed a tendency to overestimate the volume of a contrast-enhancing tumor, whereas manual analysis is prone to subjectivity, thereby causing considerable interrater variability

Hair cortisol concentration in veal calves reared under two different welfare production labels

The hypothesis of this study was that veal calves reared under enhanced welfare standards undergo less stress than calves raised in a conventionally system that meets the minimal standards of the Swiss animal welfare legislation, and that this difference is reflected by differences in hair cortisol concentrations and the size, weight and total cortisol concentration of the adrenal glands. A total of 100 veal calves reared under two different animal welfare production labels were used; the labels differed with respect to stocking density and access to an outdoor area and pasture. The production labels included Quality Management and Naturafarm. Hair samples for cortisol measurement were collected from all calves and the adrenal glands were obtained at slaughter. The left adrenal gland was used for cortisol measurement and the right gland was used for histological and morphometric measurements. The median hair cortisol concentrations of the two production groups were 2.4 and 2.3 pg/mg hair, which did not differ significantly. Likewise, the median cortisol concentration of the adrenal cortex (1.7 and 1.6 μg/g), the total adrenal cortisol content (4.8 and 4.7 μg), the weights of the cortex (3.2 and 3.1 g) and medulla (1.7 and 1.7 g) and the thickness of the zona fasciculata (1430 and 1532 μm) did not differ significantly between groups. Thus, it appears that the calves of the two production labels did not suffer obvious stress. This finding notwithstanding, all veal calves deserve to be reared under optimised animal-appropriate welfare conditions