BOLD correlates of continuously fluctuating epileptic activity isolated by independent component analysis

Combined EEG/fMRI recordings offer a promising opportunity to detect brain areas with altered BOLD signal during interictal epileptic discharges (IEDs). These areas are likely to represent the irritative zone, which is itself a reflection of the epileptogenic zone. This paper reports on the imaging findings using independent component analysis (ICA) to continuously quantify epileptiform activity in simultaneously acquired EEG and fMRI. Using ICA derived factors coding for the epileptic activity takes into account that epileptic activity is continuously fluctuating with each spike differing in amplitude, duration and maybe topography, including subthreshold epileptic activity besides clear IEDs and may thus increase the sensitivity and statistical power of combined EEG/fMRI in epilepsy. Twenty patients with different types of focal and generalized epilepsy syndromes were investigated. ICA separated epileptiform activity from normal physiological brain activity and artifacts. In 16/20 patients, BOLD correlates of epileptic activity matched the EEG sources, the clinical semiology, and, if present, the structural lesions. In clinically equivocal cases, the BOLD correlates aided to attribute proper diagnosis of the underlying epilepsy syndrome. Furthermore, in one patient with temporal lobe epilepsy, BOLD correlates of rhythmic delta activity could be employed to delineate the affected hippocampus. Compared to BOLD correlates of manually identified IEDs, the sensitivity was improved from 50% (10/20) to 80%. The ICA EEG/fMRI approach is a safe, non-invasive and easily applicable technique, which can be used to identify regions with altered hemodynamic effects related to IEDs as well as intermittent rhythmic discharges in different types of epilepsy.

Prediction of soil organic carbon for Ethiopian highlands using soil spectroscopy

Soil spectroscopy was applied for predicting soil organic carbon (SOC) in the highlands of Ethiopia. Soil samples were acquired from Ethiopia’s National Soil Testing Centre and direct field sampling. The reflectance of samples was measured using a FieldSpec 3 diffuse reflectance spectrometer. Outliers and sample relation were evaluated using principal component analysis (PCA) and models were developed through partial least square regression (PLSR). For nine watersheds sampled, 20% of the samples were set aside to test prediction and 80% were used to develop calibration models. Depending on the number of samples per watershed, cross validation or independent validation were used.The stability of models was evaluated using coefficient of determination (R2), root mean square error (RMSE), and the ratio performance deviation (RPD). The R2 (%), RMSE (%), and RPD, respectively, for validation were Anjeni (88, 0.44, 3.05), Bale (86, 0.52, 2.7), Basketo (89, 0.57, 3.0), Benishangul (91, 0.30, 3.4), Kersa (82, 0.44, 2.4), Kola tembien (75, 0.44, 1.9),Maybar (84. 0.57, 2.5),Megech (85, 0.15, 2.6), andWondoGenet (86, 0.52, 2.7) indicating that themodels were stable. Models performed better for areas with high SOC values than areas with lower SOC values. Overall, soil spectroscopy performance ranged from very good to good.

Comparison of partial least squares regression and principal component regression for pelvic shape prediction.

This paper studied two different regression techniques for pelvic shape prediction, i.e., the partial least square regression (PLSR) and the principal component regression (PCR). Three different predictors such as surface landmarks, morphological parameters, or surface models of neighboring structures were used in a cross-validation study to predict the pelvic shape. Results obtained from applying these two different regression techniques were compared to the population mean model. In almost all the prediction experiments, both regression techniques unanimously generated better results than the population mean model, while the difference on prediction accuracy between these two regression methods is not statistically significant (α=0.01).

Circulating microRNA profiling in patients with advanced non-squamous NSCLC receiving bevacizumab/erlotinib followed by platinum-based chemotherapy at progression (SAKK 19/05).

OBJECTIVES Molecular subclassification of non small-cell lung cancer (NSCLC) is essential to improve clinical outcome. This study assessed the prognostic and predictive value of circulating micro-RNA (miRNA) in patients with non-squamous NSCLC enrolled in the phase II SAKK (Swiss Group for Clinical Cancer Research) trial 19/05, receiving uniform treatment with first-line bevacizumab and erlotinib followed by platinum-based chemotherapy at progression. MATERIALS AND METHODS Fifty patients with baseline and 24 h blood samples were included from SAKK 19/05. The primary study endpoint was to identify prognostic (overall survival, OS) miRNA's. Patient samples were analyzed with Agilent human miRNA 8x60K microarrays, each glass slide formatted with eight high-definition 60K arrays. Each array contained 40 probes targeting each of the 1347 miRNA. Data preprocessing included quantile normalization using robust multi-array average (RMA) algorithm. Prognostic and predictive miRNA expression profiles were identified by Spearman's rank correlation test (percentage tumor shrinkage) or log-rank testing (for time-to-event endpoints). RESULTS Data preprocessing kept 49 patients and 424 miRNA for further analysis. Ten miRNA's were significantly associated with OS, with hsa-miR-29a being the strongest prognostic marker (HR=6.44, 95%-CI 2.39-17.33). Patients with high has-miR-29a expression had a significantly lower survival at 10 months compared to patients with a low expression (54% versus 83%). Six out of the 10 miRNA's (hsa-miRN-29a, hsa-miR-542-5p, hsa-miR-502-3p, hsa-miR-376a, hsa-miR-500a, hsa-miR-424) were insensitive to perturbations according to jackknife cross-validation on their HR for OS. The respective principal component analysis (PCA) defined a meta-miRNA signature including the same 6 miRNA's, resulting in a HR of 0.66 (95%-CI 0.53-0.82). CONCLUSION Cell-free circulating miRNA-profiling successfully identified a highly prognostic 6-gene signature in patients with advanced non-squamous NSCLC. Circulating miRNA profiling should further be validated in external cohorts for the selection and monitoring of systemic treatment in patients with advanced NSCLC.

Transcriptional analysis of left-sided colitis, pancolitis, and ulcerative colitis-associated dysplasia.

BACKGROUND It is unknown why patients with extensive ulcerative colitis (UC) have a higher risk of colorectal cancer compared with patients with left-sided UC. This study characterizes the inflammatory processes in left-sided UC, pancolitis, and UC-associated dysplasia at the transcriptional level to identify potential biomarkers and transcripts of importance for the carcinogenic behavior of chronic inflammation. METHODS The Affymetrix GeneChip Human Genome U133 Plus 2.0 was applied on colonic biopsies from UC patients with left-sided UC, pancolitis, dysplasia, and controls. Reverse transcription polymerase chain reaction and immunohistochemistry were performed for validating selected transcripts in the initial cohort and in 2 independent cohorts of patients with UC. Microarray data were analyzed by principal component analysis, and reverse transcription polymerase chain reaction and immunohistochemistry data by the Wilcoxon's rank-sum test. RESULTS The principal component analysis results revealed separate clusters for left-sided UC, pancolitis, dysplasia, and controls. Close clustering of dysplastic and pancolitic samples indicated similarities in gene expression. Indeed, 101 and 656 parallel upregulated and downregulated transcripts, respectively, were identified in specimens from dysplasia and pancolitis. Validation of selected transcripts hereof identified insulin receptor alpha (INSRA) and MAP kinase interacting serine/threonine kinase 2 (MKNK2) with an enhanced expression in dysplasia compared with left-sided UC and controls, whereas laminin γ2 (LAMC2) was found with a lower expression in dysplasia compared with the remaining 3 groups. CONCLUSIONS This study demonstrates pancolitis and left-sided UC as distinct inflammatory processes at the transcriptional level, and identifies INSRA, MKNK2, and LAMC2 as potential critical transcripts in the inflammation-driven preneoplastic process of UC.

Visible near infra-red (VisNIR) spectroscopy for predicting soil organic carbon in Ethiopia

Over the past few decades, the advantages of the visible-near infra-red (VisNIR) diffuse reflectance spectrometer (DRS) method have enabled prediction of soil organic carbon (SOC). In this study, SOC was predicted using regression models for samples taken from three sites (Gununo, Maybar and Anjeni) in Ethiopia. SOC was characterized in laboratory using conventional wet chemistry and VisNIR-DRS methods. Principal component analysis (PCA), principal component regression (PCR) and partial least square regression (PLS) models were developed using Unscrambler X 10.2. PCA results show that the first two components accounted for a minimum of 96% variation which increased for individual sites and with data treatments. Correlation (r), coefficient of determination (R2) and residual prediction deviation (RPD) were used to rate four models built. PLS model (r, R2, RPD) values for Anjeni were 0.9, 0.9 and 3.6; for Gununo values 0.6, 0.3 and 1.2; for Maybar values 0.6, 0.3 and 0.9, and for the three sites values 0.7, 0.6 and 1.5, respectively. PCR model values (r, R2, RPD) for Anjeni were 0.9, 0.8 and 2.7; for Gununo values 0.5, 0.3 and 1; for Maybar values 0.5, 0.1 and 0.7, and for the three sites values 0.7, 0.5 and 1.2, respectively. Comparison and testing of models shows superior performance of PLS to PCR. Models were rated as very poor (Maybar), poor (Gununo and three sites) and excellent (Anjeni). A robust model, Anjeni, is recommended for prediction of SOC in Ethiopia.

Geographic variation in floral allometry suggests repeated transitions between selfing and outcrossing in a mixed mating plant

• Premise of the study: Isometric and allometric scaling of a conserved floral plan could provide a parsimonious mechanism for rapid and reversible transitions between breeding systems. This scaling may occur during transitions between predominant autogamy and xenogamy, contributing to the maintenance of a stable mixed mating system. • Methods: We compared nine disjunct populations of the polytypic, mixed mating species Oenothera flava (Onagraceae) to two parapatric relatives, the obligately xenogamous species O. acutissima and the mixed mating species O. triloba. We compared floral morphology of all taxa using principal component analysis (PCA) and developmental trajectories of floral organs using ANCOVA homogeneity of slopes. • Key results: The PCA revealed both isometric and allometric scaling of a conserved floral plan. Three principal components (PCs) explained 92.5% of the variation in the three species. PC1 predominantly loaded on measures of floral size and accounts for 36% of the variation. PC2 accounted for 35% of the variation, predominantly in traits that influence pollinator handling. PC3 accounted for 22% of the variation, primarily in anther–stigma distance (herkogamy). During O. flava subsp. taraxacoides development, style elongation was accelerated relative to anthers, resulting in positive herkogamy. During O. flava subsp. flava development, style elongation was decelerated, resulting in zero or negative herkogamy. Of the two populations with intermediate morphology, style elongation was accelerated in one population and decelerated in the other. • Conclusions: Isometric and allometric scaling of floral organs in North American Oenothera section Lavauxia drive variation in breeding system. Multiple developmental paths to intermediate phenotypes support the likelihood of multiple mating system transitions.

Climate sensitivity of Mediterranean pine growth reveals distinct east-west dipole

The European Mediterranean region is governed by a characteristic climate of summer drought that is likely to increase in duration and intensity under predicted climate change. However, large-scale network analyses investigating spatial aspects of pre-instrumental drought variability for this biogeographic zone are still scarce. In this study we introduce 54 mid- to high-elevation tree-ring width (TRW) chronologies comprising 2186 individual series from pine trees (Pinus spp.). This compilation spans a 4000-km east–west transect from Spain to Turkey, and was subjected to quality control and standardization prior to the development of site chronologies. A principal component analysis (PCA) was applied to identify spatial growth patterns during the network's common period 1862–1976, and new composite TRW chronologies were developed and investigated. The PCA reveals a common variance of 19.7% over the 54 Mediterranean pine chronologies. More interestingly, a dipole pattern in growth variability is found between the western (15% explained variance) and eastern (9.6%) sites, persisting back to 1330 AD. Pine growth on the Iberian Peninsula and Italy favours warm early growing seasons, but summer drought is most critical for ring width formation in the eastern Mediterranean region. Synoptic climate dynamics that have been in operation for the last seven centuries have been identified as the driving mechanism of a distinct east–west dipole in the growth variability of Mediterranean pines.

Morphological variation within the diatom taxon Cyclotella comensis and its importance for quantitative temperature reconstructions

1. The morphologically complex taxon Cyclotella comensis Grunow had no clear relationship with environmental parameters in a study using sediment surface samples from the Swiss Alps. The morphological heterogeneity of the taxon was investigated by applying a principal component analysis (PCA) to 9000 presence/absence descriptions of valves from surface samples of six lakes from different altitudes (15 characteristics, 100 valves each lake). The PCA allowed the classification of six morphs, which differed mainly in size and length of striae. Photographs of the morphs are shown in this paper. 2. Sixty-eight sediment surface samples were analysed using these newly defined six morphs. Summer temperature explained a major part of the variance between the morphs as assessed by a redundancy analysis (RDA). Summer temperature optima and tolerances were estimated using weighted averaging. 3. The influence of the revised C. comensis taxonomy on the diatom inferred summer temperature of a high alpine lake is discussed in a multiproxy context for the past 800 years.