Comprehensive analysis of correlation coefficients estimated from pooling heterogeneous microarray data

Background The synthesis of information across microarray studies has been performed by combining statistical results of individual studies (as in a mosaic), or by combining data from multiple studies into a large pool to be analyzed as a single data set (as in a melting pot of data). Specific issues relating to data heterogeneity across microarray studies, such as differences within and between labs or differences among experimental conditions, could lead to equivocal results in a melting pot approach. Results We applied statistical theory to determine the specific effect of different means and heteroskedasticity across 19 groups of microarray data on the sign and magnitude of gene-to-gene Pearson correlation coefficients obtained from the pool of 19 groups. We quantified the biases of the pooled coefficients and compared them to the biases of correlations estimated by an effect-size model. Mean differences across the 19 groups were the main factor determining the magnitude and sign of the pooled coefficients, which showed largest values of bias as they approached ±1. Only heteroskedasticity across the pool of 19 groups resulted in less efficient estimations of correlations than did a classical meta-analysis approach of combining correlation coefficients. These results were corroborated by simulation studies involving either mean differences or heteroskedasticity across a pool of N \u3e 2 groups. Conclusions The combination of statistical results is best suited for synthesizing the correlation between expression profiles of a gene pair across several microarray studies

Blood lead, cadmium and mercury among children from urban, industrial and rural areas of Fez Boulemane Region (Morocco): Relevant factors and early renal effects

Objectives: To describe blood lead (Pb-B), cadmium (Cd-B) and mercury (Hg-B) levels in children living in urban, industrial and rural areas in Fez city (north of Morocco) and to identify the determinants and some renal effects of exposure. Material and Methods: The study was conducted from June 2007 to January 2008 in 209 school children (113 girls, 96 boys), aged 6-12 years, from urban, industrial and rural areas in Fez city. Interview and questionnaires data were obtained. Blood and urinary samples were analyzed. Results: The mean of blood lead levels (Pb-B) in our population was 55.53 μg/l (range: 7.5-231.1 μg/l). Children from the urban area had higher blood lead levels (BLLs) mean (82.36 μg/l) than children from industrial and rural areas (48.23 and 35.99 μg/l, respectively); with no significant difference between boys and girls. BLLs were associated with traffic intensity, passive smoking and infancy in the urban area. The mean of blood cadmium levels (BCLs) was 0.22 μg/l (range: 0.06-0.68 μg/l), with no difference between various areas. Rural boys had higher BCLs mean than rural girls, but no gender influence was noticed in the other areas. BCLs were associated with the number of cigarettes smoked at children's homes. The blood mercury levels (BMLs) mean was 0.49 μg/l (range: 0.01-5.31 μg/l). The BMLs mean was higher in urban and industrial areas than in the rural area with no gender-related difference. BMLs were associated with amalgam fillings and infancy in the urban area. About 8% of the children had BLLs ≥ 100 μg/l particularly in the urban area, microalbuminuria and a decrease in height were noticed in girls from the inner city of Fez and that can be related to high BLLs (89.45 μg/l). Conclusions: There is a need to control and regulate potential sources of contamination by these trace elements in children; particularly for lead

Early loss of Crebbp confers malignant stem cell properties on lymphoid progenitors.

Loss-of-function mutations of cyclic-AMP response element binding protein, binding protein (CREBBP) are prevalent in lymphoid malignancies. However, the tumour suppressor functions of CREBBP remain unclear. We demonstrate that loss of Crebbp in murine haematopoietic stem and progenitor cells (HSPCs) leads to increased development of B-cell lymphomas. This is preceded by accumulation of hyperproliferative lymphoid progenitors with a defective DNA damage response (DDR) due to a failure to acetylate p53. We identify a premalignant lymphoma stem cell population with decreased H3K27ac, which undergoes transcriptional and genetic evolution due to the altered DDR, resulting in lymphomagenesis. Importantly, when Crebbp is lost later in lymphopoiesis, cellular abnormalities are lost and tumour generation is attenuated. We also document that CREBBP mutations may occur in HSPCs from patients with CREBBP-mutated lymphoma. These data suggest that earlier loss of Crebbp is advantageous for lymphoid transformation and inform the cellular origins and subsequent evolution of lymphoid malignancies

A Fluorescent Glycolipid-Binding Peptide Probe Traces Cholesterol Dependent Microdomain-Derived Trafficking Pathways

10.1371/journal.pone.0002933PLoS ONE38

ICAR: endoscopic skull‐base surgery

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Why Are Outcomes Different for Registry Patients Enrolled Prospectively and Retrospectively? Insights from the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF).

Background: Retrospective and prospective observational studies are designed to reflect real-world evidence on clinical practice, but can yield conflicting results. The GARFIELD-AF Registry includes both methods of enrolment and allows analysis of differences in patient characteristics and outcomes that may result. Methods and Results: Patients with atrial fibrillation (AF) and ≥1 risk factor for stroke at diagnosis of AF were recruited either retrospectively (n = 5069) or prospectively (n = 5501) from 19 countries and then followed prospectively. The retrospectively enrolled cohort comprised patients with established AF (for a least 6, and up to 24 months before enrolment), who were identified retrospectively (and baseline and partial follow-up data were collected from the emedical records) and then followed prospectively between 0-18 months (such that the total time of follow-up was 24 months; data collection Dec-2009 and Oct-2010). In the prospectively enrolled cohort, patients with newly diagnosed AF (≤6 weeks after diagnosis) were recruited between Mar-2010 and Oct-2011 and were followed for 24 months after enrolment. Differences between the cohorts were observed in clinical characteristics, including type of AF, stroke prevention strategies, and event rates. More patients in the retrospectively identified cohort received vitamin K antagonists (62.1% vs. 53.2%) and fewer received non-vitamin K oral anticoagulants (1.8% vs . 4.2%). All-cause mortality rates per 100 person-years during the prospective follow-up (starting the first study visit up to 1 year) were significantly lower in the retrospective than prospectively identified cohort (3.04 [95% CI 2.51 to 3.67] vs . 4.05 [95% CI 3.53 to 4.63]; p = 0.016). Conclusions: Interpretations of data from registries that aim to evaluate the characteristics and outcomes of patients with AF must take account of differences in registry design and the impact of recall bias and survivorship bias that is incurred with retrospective enrolment. Clinical Trial Registration: - URL: http://www.clinicaltrials.gov . Unique identifier for GARFIELD-AF (NCT01090362)