Mcgeesutherland1756

INTRODUCTION Meta-analysis is a powerful means for leveraging the hundreds of experiments being run worldwide into more statistically powerful analyses. This is also true for the analysis of omic data, including genome-wide DNA methylation. In particular, thousands of DNA methylation profiles generated using the Illumina 450k are stored in the publicly accessible Gene Expression Omnibus (GEO) repository. Often, however, the intensity values produced by the BeadChip (raw data) are not deposited, therefore only pre-processed values -obtained after computational manipulation- are available. Pre-processing is possibly different among studies and may then affect meta-analysis by introducing non-biological sources of variability. MATERIAL AND METHODS To systematically investigate the effect of pre-processing on meta-analysis, we analysed four different collections of DNA methylation samples (datasets), each composed of two subsets, for which raw data from controls (i.e. healthy subjects) and cases (i.e. patients) are available. We pre-processed the data from each dataset with nine among the most common pipelines found in literature. Moreover, we evaluated the performance of regRCPqn, a modification of the RCP algorithm that aims to improve data consistency. For each combination of pre-processing (9 × 9), we first evaluated the between-sample variability among control subjects and, then, we identified genomic positions that are differentially methylated between cases and controls (differential analysis). RESULTS AND CONCLUSION The pre-processing of DNA methylation data affects both the between-sample variability and the loci identified as differentially methylated, and the effects of pre-processing are strongly dataset-dependent. By contrast, application of our renormalization algorithm regRCPqn (i) reduces variability and (ii) increases agreement between meta-analysed datasets, both critical components of data harmonization.We aimed to construct a better model for predicting treatment outcomes of anti-vascular endothelial growth factor therapy for neovascular age-related macular degeneration (nAMD) using the concentrations of aqueous humour proteins at baseline and during treatment. From the data of 48 treatment-naïve nAMD eyes that received intravitreal ranibizumab pro re nata for up to 12 months, we used the aqueous humour concentrations of C-X-C motif chemokine ligand 1 (CXCL1), CXCL12, CXCL13, interferon-γ-induced protein 10, monocyte chemoattractant protein 1 (MCP-1), C-C motif chemokine ligand 11, interleukin 6 (IL-6), IL-10, and matrix metalloproteinase 9 (MMP-9). After stepwise regression, multivariate analysis was performed to identify which predictors were significantly associated with best-corrected visual acuity (BCVA) changes and the number of injections. The results demonstrated that besides male sex (β coefficient = -0.088, P = 0.040) and central retinal thickness (β coefficient = 0.00051 per μm, P = 0.027), MCP-1 (β coefficient = 0.44, P less then 0.001) and IL-10 (β coefficient = -0.16, P = 0.033) were significantly correlated with baseline BCVA. Additionally, high MCP-1 at baseline (β coefficient = -0.20, P = 0.015) and low CXCL13 at baseline (β coefficient = 0.10, P = 0.0054) were independently associated with better BCVA change at 12 months. High MMP-9 at the first injection (β coefficient = 0.56, P = 0.01), CXCL12 at the third injection (β coefficient = 0.10, P = 0.0002), and IL-10 at the third injection (β coefficient = 1.3, P = 0.001) were predictor variables associated with the increased number of injections. In conclusion, aqueous humour protein concentrations may have predictive abilities of BCVA change over 12 months and the number of injections in pro re nata treatment of exudative nAMD.BACKGROUND About 50% of the patients 5-7 years after kidney transplantation show impairment of memory, attention and executive function. Tacrolimus frequently induces neurological complications in the first few weeks after transplantation. Furthermore, tacrolimus treatment is associated with impaired cognitive function in the long-term in patients after liver transplantation. We hypothesize that long-term tacrolimus therapy is associated with cognitive dysfunction and alterations of brain structure and metabolism in patients after kidney transplantation. METHODS Twenty-one patients 10 years after kidney transplantation underwent cognitive testing, magnetic resonance imaging and whole brain 31-phosphor magnetic resonance spectroscopy for the assessment of brain function, structure and energy metabolism. Using a cross-sectional study design the results were compared to those of patients 1 (n = 11) and 5 years (n = 10) after kidney transplantation, and healthy controls (n = 17). To further analyze the share of transplantation, tacrolimus therapy and kidney dysfunction on the results patients after liver transplantation (n = 9) were selected as a patient control group. selleck compound RESULTS Patients 1 and 10 years after kidney transplantation (p = 0.02) similar to patients 10 years after liver transplantation (p less then 0.01) showed significantly worse cognitive function than healthy controls. In contrast to patients after liver transplantation patients after kidney transplantation showed significantly reduced adenosine triphosphate levels in the brain compared to healthy controls (p≤0.01). Patients 1 and 5 years after kidney transplantation had significantly increased periventricular hyperintensities compared to healthy controls (p less then 0.05). CONCLUSIONS Our data indicate that cognitive impairment in the long-term after liver and kidney transplantation cannot exclusively be explained by CNI neurotoxicity.In this study, the presence of Leishmania DNA and blood feeding sources in phlebotomine sand fly species commonly present in Sicily were investigated. A total of 1,866 female sand flies including 176 blood fed specimens were sampled over two seasons in five selected sites in Sicily (southern Italy). Sergentomyia minuta (n = 1,264) and Phlebotomus perniciousus (n = 594) were the most abundant species at all the sites, while three other species from the genus Phlebotomus (i.e., P. sergenti n = 4, P. perfiliewi n = 3 and P. neglectus n = 1) were only sporadically captured. Twenty-eight out of the 1,866 (1.5%) sand flies tested positive for Leishmania spp. Leishmania tarentolae DNA was identified in 26 specimens of S. minuta, while the DNA of Leishmania donovani complex was detected in a single specimen each of S. minuta and P. perniciosus. Interestingly, seven S. minuta specimens (0.4%) tested positive for reptilian Trypanosoma sp. Blood sources were successfully identified in 108 out of 176 blood fed females. Twenty-seven out of 82 blood sources identified in fed females of P.