Nonlinear analysis of bivariate data with cross recurrence plots

We use the extension of the method of recurrence plots to cross recurrence plots (CRP) which enables a nonlinear analysis of bivariate data. To quantify CRPs, we develop further three measures of complexity mainly basing on diagonal structures in CRPs. The CRP analysis of prototypical model systems with nonlinear interactions demonstrates that this technique enables to find these nonlinear interrelations from bivariate time series, whereas linear correlation tests do not. Applying the CRP analysis to climatological data, we find a complex relationship between rainfall and El Nino data

Microsurgery can cure most intracranial dural arteriovenous fistulae of the sinus and non-sinus type

There is consensus that intracranial dural arteriovenous fistulae (dAVF) with direct (non-sinus-type) or indirect (sinus-type) retrograde filling of a leptomeningeal vein should be treated due to the high risk of neurological deficits and hemorrhage. No consensus exists on treatment modality (surgery and/or embolization) and, if surgery is performed, on the best surgical strategy. This series aims to evaluate the role of surgery in the management of aggressive dAVFs. Forty-two patients underwent surgery. Opening and packing the sinus with thrombogenic material was performed in 9 of the 12 sinus-type dAVFs. In two sinus-type fistulae of the cavernous sinus and 1 of the torcular, microsurgery was used as prerequisite for subsequent embolization by providing access to the sinus. In the 30 non-sinus-type dAVFs, surgery consisted of interruption of the draining vein at the intradural entry point. In 41 patients undergoing 43 operations, elimination of the dAVF was achieved (97.6%). In one case, a minimal venous drainage persisted after surgery. The transient surgical morbidity was 11.9% (n = 5) and the permanent surgical morbidity 7.1% (n = 3). Our surgical strategy was to focus on the arterialized leptomeningeal vein in the non-sinus-type and on the arterialized sinus segment in the sinus-type dAVFs allowing us to obliterate all but one dAVF with a low morbidity rate. We therefore propose that microsurgery should be considered early in the treatment of both types of aggressive dAVFs. In selected cases of cavernous sinus dAVFs, the role of microsurgery is reduced to that of an adjunct to endovascular therapy

supplementary figures

Supplementary figure S1: Principal component analysis on normalized gene expression data. The distance between points approximates gene expression pattern differences among groupings. PCA identified two distinct clusters in the data separated along the second principal component. Clustering was associated with the source of the samples that can be assigned to GTEx samples and corpus and antrum samples. Corpus and antrum samples cluster closest to GTEx stomach samples compared to other tissues from GTEx. Supplementary figure S2: Unsupervised hierarchical clustering of the top 100 most variable expressed genes using RNA sequencing expression data of tissue biopsies taken from the corpus (N=362) and antrum (N=342) from a total of 431 individuals. Gene expression values were row Z-score normalized where lower expression is denoted by blue and higher expression by red color. Substantial differential gene expression between both stomach regions was observed. The covariates sex and batch had less influence. Supplementary figure S3: Enrichment of DEG sets in site-specific gene sets with the highest relative expression in corpus (A) and antrum (B). Enrichment analyses were performed using the GTEx v8 30 general tissue types database in FUMA GENE2FUNC. Pre-calculated differentially expressed genes (DEG) sets were created of each of the GTEx v8 tissue expression data set. DEG sets were obtained by a two-sided t-test per tissue versus all the remaining tissues. Up-regulated DEG sets contained all genes that were significantly overexpressed in the tissue compared to other tissues. Significantly enriched DEG sets (Bonferroni corrected P-value Supplementary figure S4: Functional enrichment analysis of the gene ontology (GO) biological process subset. Linkages between genes and the five most significantly enriched GO terms for corpus (A) and antrum (B) are shown as a network. The fold changes of the genes associated with these terms are color-coded: genes with a high expression in the stomach region compared to other tissues are depicted in red, genes with a low expression in the stomach region compared to other tissues are depicted in blue. The size of the GO terms reflects the number of associated genes. Supplementary figure S5: Exemplary conditional analysis of a TWAS-significant locus on 18q21 (trait = body mass index). The top panel of the joint/conditional plot highlights all genes that are located in the locus (usually grey). Jointly significant genes that are responsible for most GWAS signals in the region are marked in green, marginally associated TWAS genes (i.e. genes that are no longer significant after accounting for conditionally independent genes) are shown in blue. The bottom panel shows a regional manhattan plot of GWAS data before (grey) and after (blue) conditioning on the predicted expression of the jointly-significant genes (here: RAB27B). Supplementary figure S6: PheWas manhattan plots for rs2075571 (A) and rs12456732 (B). Each data point represents the significance of association between the respective SNP and different phenotypes. Data is grouped and color-coded according to phenotype groups. The dashed line represents the threshold for phenome-wide significance (P-value = 1x10-9) and significant SNP-phenotype associations are text-labeled. Supplementary figure S7: Correlation analysis of eQTL and GWAS P-values to assess colocalization of variants associated with serum urea levels and MUC1 eQTL (A) and RAB27B eQTL and BMI-associated variants (B). Color coding differentiates between eQTL with positive or negative effect sizes beta. R is the Pearson correlation coefficient and P represents the P-value of correlation.</p

supplementary_tables.xlsx

supplementary tables</p