Central nervous system relapse in high-risk stage 4 neuroblastoma: The HR-NBL1/SIOPEN trial experience.

BACKGROUND: There is rising concern on the impact of new strategies, such as high-dose chemotherapy (HDC) and immunotherapy, on the pattern of relapse in high-risk neuroblastoma (HR-NBL). Our aim is to evaluate the incidence and identify risk factors for first recurrence in the central nervous system (CNS) in HR-NBL. PATIENTS AND METHODS: Data from patients with stage 4V HR-NBL included from February 2002 to June 2015 in the prospective HR-NBL trial of the European International Society of Pediatric Oncology Neuroblastoma Group were analysed. Characteristics at diagnosis, treatment and the pattern of first relapse were studied. CNS imaging at relapse was centrally reviewed. RESULTS: The 1977 included patients had a median age of 3 years (1 day-20 years); 1163 were boys. Among the 1161 first relapses, 53 were in the CNS, with an overall incidence of 2.7%, representing 6.2% of all metastatic relapses. One- and three-year post-relapse overall survival was 25 ± 6% and 8 ± 4%, respectively. Higher risk of CNS recurrence was associated with female sex (hazard ratio [HR] = 2.0 [95% confidence interval {CI}: 1.1-3.5]; P = 0.016), MYCN-amplification (HR = 2.4 [95% CI: 1.2-4.4]; P = 0.008), liver (HR = 2.5 [95% CI: 1.2-5.1]; P = 0.01) or >1 metastatic compartment involvement (HR = 7.1 [95% CI: 1.0-48.4]; P = 0.047) at diagnosis. Neither HDC nor immunotherapy was associated with higher risk of CNS recurrence. Stable incidence of CNS relapse was reported over time. CONCLUSIONS: The risk of CNS recurrence is linked to both patient and disease characteristics, with neither impact of HDC nor immunotherapy. These findings support the current treatment strategy and do not justify a CNS prophylactic treatment.

Cardiac anomaly detection based on time and frequency domain features using tree-based classifiers.

OBJECTIVE: Recent advantages in mHealth-enabled ECG recorders boosted the demand for algorithms, which are able to automatically detect cardiac anomalies with high accuracy. APPROACH: We present a combined method of classical signal analysis and machine learning which has been developed during the Computing in Cardiology Challenge (CinC) 2017. Almost 400 hand-crafted features have been developed to reflect the complex physiology of cardiac arrhythmias and their appearance in single-channel ECG recordings. For the scope of this article, we performed several experiments on the publicly available challenge dataset to improve the classification accuracy. We compared the performance of two tree-based algorithms-gradient boosted trees and random forests-using different parameters for learning. We assessed the influence of five different sets of training annotations on the classifiers performance. Further, we present a new web-based ECG viewer to review and correct the training labels of a signal data set. Moreover, we analysed the feature importance and evaluated the model performance when using only a subset of the features. The primary data source used in the analysis was the dataset of the CinC 2017, consisting of 8528 signals from four classes. Our best results were achieved using a gradient boosted tree model which worked significantly better than random forests. MAIN RESULTS: Official results of the challenge follow-up phase provided by the Challenge organizers on the full hidden test set are 90.8% (Normal), 84.1% (AF), 74.5% (Other), resulting in a mean F1-score of 83.2%, which was only 1.6% behind the challenge winner and 0.2% ahead of the next-best algorithm. Official results were rounded to two decimal places which lead to the equal-second best F1 F -score of 83% with five others. SIGNIFICANCE: The algorithm achieved the second-best score among 80 algorithms of the Challenge follow-up phase equal with five others.

DNA barcoding of crickets, katydids and grasshoppers (Orthoptera) from Central Europe with focus on Austria, Germany and Switzerland.

We present a DNA barcoding study on the insect order Orthoptera that was generated in collaboration between four barcoding projects in three countries, viz. Barcoding Fauna Bavarica (Germany), German Barcode of Life, Austrian Barcode of Life and Swiss Barcode of Life. Our data set includes 748 COI sequences from 127 of the 162 taxa (78.4%) recorded in the three countries involved. Ninety-three of these 122 species (76.2%, including all Ensifera) can be reliably identified using DNA barcodes. The remaining 26 caeliferan species (families Acrididae and Tetrigidae) form ten clusters that share barcodes among up to five species, in three cases even across different genera, and in six cases even sharing individual barcodes. We discuss incomplete lineage sorting and hybridization as most likely causes of this phenomenon, as the species concerned are phylogenetically young and hybridization has been previously observed. We also highlight the problem of nuclear mitochondrial pseudogenes (numts), a known problem in the barcoding of orthopteran species, and the possibility of Wolbachia infections. Finally, we discuss the possible taxonomic implications of our barcoding results and point out future research directions.

Genetic and reproductive characterisation of seasonal flowering morphs of Gentianella bohemica revealed strong reproductive isolation and possible single origin.

Phenotypic polymorphism represents the most obvious type of intraspecific diversity raising scientific interest in its evolution and maintenance. We studied the regional endemic Gentianella bohemica, which exhibits an early- and a late-flowering morph. Genetic variation and structuring were investigated in relation to potential pollination and mating system differences, to verify hypotheses of evolutionary integrity, origin, and reproductive isolation of both flowering morphs. We identified the rarer early-flowering morph as an independent genetic entity, being more selfing, likely stronger pollinator-limited and reproductively isolated. All analysed populations showed strong among population differentiation and low overall genetic diversity due to habitat fragmentation and reduced population sizes. These results indicate likely inbreeding, but we also found evidence for possible outbreeding depression in the late-flowering morph. Both G. bohemica morphs are characteristic of traditionally used, nutrient-poor grasslands, but they represent independent conservation units and need temporally adapted management. We, therefore, also briefly discuss our results in the general context of conservation activities in relation to intraspecific polymorphisms and strongly argue for their formal and consequent consideration.

The intraspecific genetic variability of siliceous and calcareous Gentiana species is shaped by contrasting demographic and re-colonization processes.

The Ciminalis section of Gentiana comprises seven species, two of them growing on siliceous substrates (G. alpina and G. acaulis), the other ones being calcareous taxa (G. clusii, G. angustifolia, G. ligustica, G. occidentalis and G. dinarica). A total of 515 individuals from 183 populations over the entire Ciminalis distribution range was analyzed using four chloroplast loci (trnH-psbA, matK, rpoB and rpoC1) and the nuclear ribosomal marker ITS2. The siliceous species display only two chloroplast haplotypes each and are both characterized by patterns of range expansions all over the Alps. Conversely, the calcareous species are on average more diverse (two to 13 haplotypes per species) with strong patterns of local structuring. We suggest that the occurrence of many calcareous refugia at the periphery of the Alps must have led to local adaptation and morphological diversification, and helped preserving intraspecific diversities during the last glaciations for the associated taxa. ITS2 was more efficient in delineating species boundaries than the chloroplast markers for which several haplotypes are shared among species. This might be either due to chloroplast capture among species and/or to recent divergence. Species adapted to the same substrate are generally only distantly related when they co-occur in the same place. For both types of markers, G. clusii is found genetically distant from all other species.

Screening for bacteremia in sepsis and renal failure using hemofilters for renal replacement therapy.

BACKGROUND: In patients with sepsis and renal failure, extracorporeal blood flow during renal replacement therapy may lead to the deposition of bacteria on artificial membranous surfaces, which might be suitable for the detection of pathogens. We studied whether discarded dialysis hemofilters can be used for the detection of bacteremia in patients with sepsis and renal failure. METHODS: Hemofilters of 16 ICU patients with sepsis were sampled. The hemofilters were incubated with soy broth and dehisced under sterile conditions. Samples were plated on blood agar and analyzed. Patient's characteristics were assessed. RESULTS: Despite the use of antibiotics in 87.5 % (14/16), a true positive detection rate of 31.3 % (5/16) for bacteremia was found by using cultures from hemofilters. The overall true positive rate of blood cultures was significantly lower (10.7 %, 8/75, p = 0.048). Bacteria detected in hemofilters were similar to those found in blood cultures or by cultures from other sources of infection in 80 % (4/5). CONCLUSIONS: Cultures from used hemofilters of patients with sepsis and renal failure provide the opportunity to identify pathogenic microorganisms as an add-on approach. Further studies should investigate whether this method is applicable in clinical practice to enhance the sensitivity of microbiological diagnostics.

Neuronal enriched endosomal protein of 21 kDa colocalizes with glutamate receptor subunit GLUR2/3 at the postsynaptic membrane.

Functional evidence suggests that neuronal enriched endosomal protein of 21 kDa (NEEP21) takes part in facilitating transport of AMPA receptors (AMPAR) in the synapse. To explore the anatomical basis for a role in this synaptic trafficking, we investigated the ultrastructural localization of NEEP21 in rodent brain. Using immunogold electron microscopy, we show that NEEP21 is colocalized with the AMPAR subunits GluR2/3 in postsynaptic spines. Quantitative analysis of gold particle distribution along an axis perpendicular to the postsynaptic specialization indicated that NEEP21 occurs in the postsynaptic membrane but also in the interior of the spines. NEEP21 positive endosomes/multivesicular bodies were found throughout cell bodies and dendrites. In light microscopical preparations, the NEEP21 antibody produced a labeling pattern in the neocortex, hippocampus and cerebellum that mimicked that of GluR2/3 and not that of GluR1 or 4. Our findings are consistent with a role for NEEP21 in facilitating vesicular transport of GluR2 between intracellular compartments and the postsynaptic plasma membrane.

Unrecognized durotomy after lumbar discectomy: a report of four cases associated with the use of ADCON-L.

STUDY DESIGN: This report describes four cases of symptomatic cerebral spinal fluid leak after lumbar microdiscectomy where ADCON-L was used. OBJECTIVES: To report that ADCON-L may exacerbate cerebral spinal fluid leak from unrecognized, small dural tears after lumbar discectomy. SUMMARY OF BACKGROUND DATA: ADCON-L is a porcine-derived polyglycan that is used with increasing frequency in spinal surgery. It is advocated to reduce postoperative peridural fibrosis and adhesions. METHODS: Four cases of symptomatic cerebral spinal fluid leak after lumbar microdiscectomy were identified. Information on these patients was obtained by chart review. RESULTS: Three patients had small, inadvertent durotomies that were not appreciated at surgery even with the aid of a microscope. The dural violation in the fourth patient occurred at the previous epidural steroid injection site located on the contralateral side of the laminotomy. CONCLUSION: ADCON-L may inhibit dural healing and exacerbate cerebral spinal fluid leak from microscopic durotomies not recognized at the time of surgery.

Optoelectronic evaluation of trunk deformity in scoliosis.

In this study, truncal deformity in patients with scoliosis was evaluated by circumferential scanning using an optoelectronic device (Optronic Torsograph, Anima Corp., Tokyo, Japan). This device generates cross-sectional skin surface topography at 10 axial levels to provide a three-dimensional representation of truncal shape. Ninety-three patients with suspected idiopathic scoliosis were evaluated with conventional Cobb measurements, and their parameters were computed using the device's measurements. The geometric cross-sectional indexes correlated poorly with the Cobb angle and were highly variable during repeated measurements. The optoelectronic device's angle, a measure of centroid curvature, correlated highly with the Cobb angle for primary spinal curves. The highest correlation was observed in thoracolumbar curves. This optoelectronic device has clinical relevance as a method for further scoliosis screening and monitoring the progression of spinal curvature in a patient.

Mutants of plasmid prophage P1 and elevated copy number: isolation and characterization.

A series of mutations of the P1 plasmid prophage that lead to increased copy number was isolated and analyzed. The copy number of the mutants was elevated at least five- to eightfold relative to wild-type P1, as determined by single-cell resistance to antibiotics, activity of enzymes, content of superhelical DNA, and reassociation kinetics. The copy number of two of the mutants was temperature dependent. Based on dominance tests, the mutants fell into two classes, cis specific and recessive. The latter class included a temperature-sensitive copy mutant. The existence of a class of recessive mutants suggests that the replication of the P1 plasmid is negatively regulated.