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ALK is the most commonly mutated oncogene in neuroblastoma with increased mutation frequency reported at relapse. Here we report the loss of an ALK mutation in two patients at relapse and a paired neuroblastoma cell line at relapse.\ud \ud ALK detection methods including Sanger sequencing, targeted next-generation sequencing and a new ALK Agena MassARRAY technique were used to detect common hotspot ALK variants in tumours at diagnosis and relapse from two high-risk neuroblastoma patients. Copy number analysis including single nucleotide polymorphism array and array comparative genomic hybridisation confirmed adequate tumour cell content in DNA used for mutation testing.\ud \ud Case 1 presented with an ALK F1174L mutation at diagnosis with a variant allele frequency (VAF) ranging between 23.5-28.5%, but the mutation was undetectable at relapse. Case 2 presented with an ALK R1257Q mutation at diagnosis (VAF=39-47.4%) which decreased to

Introduction International consensus recognises four molecular subgroups of medulloblastoma, each with distinct molecular features and clinical outcomes. The current gold-standard for subgroup assignment is DNA methylation microarray. There is an unmet need to develop platform-independent subgrouping assays which are both non-proprietary and compatible with rapidly-expanding WGS capacity in healthcare. Whole Genome Bisulfite Sequencing (WGBS) enables the assessment of genome-wide methylation status at single-base resolution. Previously, WGBS adoption has been limited by cost and sample quality/quantity requirements. Its application for routine detection of medulloblastoma subgroups has not previously been reported. Methodology Two datasets were utilised; 36 newly-sequenced low-depth (10x coverage) and 34 publicly-available high-depth (30x) WGBS medulloblastomas, all with matched DNA methylation microarray data. We compared platform concordance and identified molecular subgroups. Machine-learning WGBS-based subgroup classifiers were optimised and compared between platforms. Aneuploidy and mutation detection using WGBS was optimised and compared to microarray-derived estimates where possible. Finally, comprehensive subgroup-specific DNA methylation signatures were identified. Results We optimised a pipeline for processing, quality control and analysis of low-depth WGBS data, suitable for routine molecular subgrouping and aneuploidy assessment. We demonstrated the suitability of fresh-frozen and FFPE DNA for WGBS, and, using downsampling, showed that subgroup calling is robust at coverages as low as 2x. We identified differentially methylated regions that, due to poor representation, could not be detected using methylation microarrays. Molecular subgroups of medulloblastoma assigned using WGBS were concordant with array-based definitions, and WGBS-derived classifier performance measures exceeded microarray-derived classifiers. Conclusion We describe a platform-independent assay for molecular subgrouping of medulloblastoma using WGBS. It performs equivalently to current array-based methods at comparable cost ($405 vs $596) and provides a proof-of-concept for its routine clinical adoption using standard WGS technology. Finally, the full methylome enabled elucidation of additional biological heterogeneity that has hitherto been inaccessible.

INTRODUCTION: International consensus recognises four molecular subgroups of medulloblastoma, each with distinct molecular features and clinical outcomes. Assigning molecular subgroup is typically achieved via the Illumina DNA methylation microarray. Given the rapidly-expanding WGS capacity in healthcare institutions, there is an unmet need to develop platform-independent, sequence-based subgrouping assays. Whole genome bisulfite sequencing (WGBS) enables the assessment of genome-wide methylation status at single-base resolution. To date, its routine application for subgroup assignment has been limited, due to high economic cost and sample input requirements. Currently, no optimised pipeline exists that is tailored to handle samples sequenced at low-pass (i.e.

International audience; Rhodococcus strain IGTS8 is the most extensively studied model bacterium for biodesulfurization of fossil fuels via the non-destructive sulfur-specific 4S pathway. This strain was initially assigned to Rhodococcus rhodochrous and later to Rhodococcus erythropolis thus making its taxonomic status debatable and reflecting the limited resolution of methods available at the time. In this study, phylogenomic analyses of the whole genome sequences of strain IGTS8 and closely related rhodococci showed that R. erythropolis and Rhodococcus qingshengii are very closely related species, that Rhodococcus strain IGTS8 is a R. qingshengii strain and that several strains identified as R. erythropolis should be reclassified as R. qingshengii. The genomes of strains assigned to these species contain potentially novel biosynthetic gene clusters showing that members of these taxa should be given greater importance in the search for new antimicrobials and other industrially important biomolecules. The plasmid-borne dsz operon encoding fossil fuel desulfurization enzymes was present in R. qingshengii IGTS8 and R. erythropolis XP suggesting that it might be transferable between members of these species.

Two qualified and one assistant clinical psychologist delivered a modified version of Willner and Tomlinson’s (2004) CBT manual in a community setting. Service users’ reported experiences of the group and facilitators’ considerations are presented to identify process issues, both positive and negative, in order to inform future interventions. The findings are discussed in the context of the application of CBT to adults with learning disabilities after which recommendations for future group work are made. They include suggestions for: engaging support staff; enforcing agreed group rules; introducing cognitive skills; addressing community as well as individual issues; and follow-up.

We identified a series of novel 7-phenyl benzoxaborole compounds with activity against Mycobacterium tuberculosis. Compounds had a range of activity with inhibitory concentrations (IC90) as low as 5.1 μM and no cytotoxicity against eukaryotic cells (IC50 > 50 μM). Compounds were active against intracellular mycobacteria cultured in THP-1 macrophages. We isolated and characterized resistant mutants with mutations in NADH dehydrogenase (Ndh) or the regulatory protein Mce3R. Mutations suggest that Ndh may be the target of this series.

The sensitivity of 15 aquatic species, including primary producers, benthic invertebrates, cladocerans, mollusks, and fish, to MON 0818, a commercial surfactant mixture of polyoxyethylene tallow amines, was evaluated in standard acute (48-96-h) laboratory tests. In addition, the potential for chronic toxicity (8 d) was evaluated with Ceriodaphnia dubia. Exposure concentrations were confirmed. No significant effects on any endpoint were observed in the chronic test. A tier-1 hazard assessment was conducted by comparing species sensitivity distributions based on the generated data, as well as literature data, with 4 exposure scenarios. This assessment showed moderate levels of hazard (43.1% of the species exposed at or above median effective concentration levels), for a chosen worst-case scenario-unintentional direct over-spray of a 15-cm-deep body of water with the maximum label application rate for the studied formulations (Roundup Original, Vision Forestry Herbicide; 12 L formulation ha

Variation in toxicity among formulations and species makes it difficult to extrapolate results to all species and all formulations of herbicides. The authors exposed larval wood frogs (Lithobates sylvaticus) from 4 populations to 2 glyphosate-based herbicides, Roundup Weed and Grass Control® and Roundup WeatherMax®. The 96-h median lethal concentration values for both formulations varied among the populations (Roundup Weed and Grass Control, 0.14 mg acid equivalents (a.e.)/L to 1.10 mg a.e./L; Roundup WeatherMax, 4.94 mg a.e./L to 8.26 mg a.e./L), demonstrating that toxicity varies among the formulations and that susceptibility may differ among populations.

Resident visitation patterns within an assisted living facility provide insight into a resident's life satisfaction. This study investigated residents' perceptions of family and friend visitation. Thirty assisted living residents from Oklahoma participated in a comprehensive interview that included demographics, life satisfaction, visitation frequency, and perceptions of visitation patterns. A majority of the respondents (90%) perceived family and friend visitation as “important” to “very important” in their life. Visitation allows residents to reminisce with family members and friends, to fulfill the need to have outside contact, and to be reassured that they have not been forgotten. Results indicate residents do desire continued relationships with family and friends through visitation. Facilities should encourage activities involving outside members of a resident's support network and be aware of residents less visited, developing programs creating social contact and involvement.

Azadirachtins are natural insecticides derived from the neem tree. The emerald ash borer (EAB) is an exotic invasive insect pest that infests various ash tree species and has the potential for significant economic, aesthetic and ecological impacts throughout North America. The initial translocation and foliar residue dynamics of azadirachtins were examined following direct injection into white and green ash trees growing in urban scenarios as a potential control for EAB.Substantial concentrations of azadirachtins A and B [mean maxima0.98 mg kg(-1) fresh weight (f.w.)] were observed within 2 days of injecting a specifically designed formulation of azadirachtins. Foliar residues declined exponentially through time, with half-life estimates ranging from 5.1 to 12.3 days. At the time of leaf senescence, foliar residue levels approximated 0.01 mg kg(-1) f.w., strongly mitigating the potential effects of non-target biota in soil or aquatic compartments.The magnitude and duration of exposures observed in this field study were considered to be above the thresholds required for biological effectiveness against both larval and adult life stages of EAB. Results support the use of azadirachtins as an environmentally acceptable systemic insecticide for control of EAB and protection of high-value ash trees in urban environments.

The emerald ash borer, Agrilus planipennis Fairmaire (Coleoptera: Buprestidae), an invasive pest discovered in North America in 2002, is now well established and threatens ash (Fraxinus spp.) trees throughout the continent. Experiments were conducted to 1) examine the efficacy of an alternative natural pesticide, azadirachtin, to control emerald ash borer, and 2) determine foliar uptake and dissipation patterns after systemic injections of azadirachtin into trunks of small (2.2 cm diameter at breast height [dbh]), uninfested green ash trees. We found no evidence of mortality of adult beetles. In contrast, fewer larvae completed their development at dose levelsor = 1.7 mg (AI)/cm dbh and development ceased beyond the second instar at dose levelsor = 13.6 mg (AI)/cm dbh. Substantial concentrations (11.2 microg/g dry mass [SD = 7.55]) of azadirachtin were present in leaves within 7 d of treatment. After rapid initial uptake, concentrations in leaves declined logarithmically during the 55 d after injection. A similar pattern was observed in a separate experiment that examined the uptake and translocation of azadirachtin in larger green ash trees (22 cm dbh) treated with 250 mg (AI) /cm dbh with the EcoJect injection system. In another experiment, recently infested plantation green ash trees treated with dosesor = 40 mg (AI)/cm dbh had significant reductions in adult emergence approximately 1 yr postinjection. Given the inhibition of larval development, reduction of adult emergence, and the occurrence of foliar residues at biologically active concentrations, we conclude that azadirachtin is effective in protecting ash trees from emerald ash borer.

The effects of hydrogen and burst media on the burst properties of Type 304L stainless steel vessels were investigated. The purpose of the study was to compare the burst properties of hydrogen-charged stainless steel vessels burst with different media: water, helium gas, and deuterium gas. A second purpose was to provide data to improve an existing finite-element model for predicting burst behavior. Burst tests were conducted on hydrogen-charged and uncharged axially-flawed cylindrical vessels. The results indicate that samples burst pneumatically had lower volume ductility than those tested hydraulically. For pneumatic burst tests, samples burst with deuterium gas had slightly lower ductility than helium gas tests. For uncharged samples, burst pressure was not affected by burst media. For samples pre-charged with hydrogen, deuterium burst pressures were about 80% of the hydraulic or helium burst pressures. Hydrogen-charged samples had lower volume ductility and slightly higher burst pressures than uncharged samples. The results of the tests were used to verify and improve a previously developed predictive finite-element model. The existing finite-element model can qualitatively predict the expected changes in burst properties with hydrogen or tritium service, but a better material property database is required for quantitative predictions.Copyright © 2008 by Washington Savannah River Company LLC

This report documents the results of an internal DRS effort to develop an Ethernet based integrated defense system to improve defense of cities, harbors, airports, power production, energy supplies, bridges, monuments, dams and so forth. Results of the integration of multiple SCOUT LPI radars and multiple Electro-optical targeting systems will be provided, illustrating the benefits of interfacing surveillance radars with imaging sensors to confirm detection and provide visual recognition and identification. An analysis of the handover errors will be provided including errors due to; sensor platforms location and orientation uncertainty, target location measurement errors, data latency and motion prediction errors, which contribute to target handoff and the re-acquisition timeline. These predictions will be compared to measured results. The system architecture will be defined including; security, support for both stationary and moving sensor platforms, remote control of sensor systems and distribution of imagery through the network and remote diagnostics, maintenance and software upgrades. Growth capabilities include secure wireless communication to/from moving platforms, integration with sonar and seismic sensors, cooperative location of friendly forces and acoustic detection and triangulation of gunshots with automated cueing of sensors and security forces to the shooters most probable location. The use of ad hoc multi-hopping wireless networking supplements hardwire networks, augments disaster response capabilities, provides high-speed communications for moving platforms and supplements GPS outage areas.

The International Space Station (ISS) Environmental Control and Life Support System (ECLSS) is designed to be maintainable. During the 3 years since the ISS US Lab became operational, there have been numerous ECLSS Orbital Replacement Units (ORUs) launched and returned to Maintain the ECLSS operation in the US segments. The maintenance logistics have provided tools for maintenance, replaced limited life ORUs and failed ORUs, upgraded ECLSS hardware to improve reliability and placed critical spares onboard prior to need. In most cases, the removed ORUs have been returned for either failure analysis and repair or refurbishment. This paper describes the ECLSS manifesting history and maintenance events and quantifies the numbers of ECLSS items, weights, and volumes.

Supply of oxygen (O2) and hydrogen (H2) by electolyzing water in space will play an important role in meeting the National Aeronautics and Space Administration's (NASA's) needs and goals for future space missios. Both O2 and H2 are envisioned to be used in a variety of processes including crew life support, spacecraft propulsion, extravehicular activity, electrical power generation/storage as well as in scientific experiment and manufacturing processes. The Electrolysis Performance Improvement Concept Study (EPICS) flight experiment described herein is sponsored by NASA Headquarters as a part of the In-Space Technology Experiment Program (IN-STEP). The objective of the EPICS is to further contribute to the improvement of the SEF technology, specifially by demonstrating and validating the SFE electromechanical process in microgravity as well as investigating perrformance improvements projected possible in a microgravity environment. This paper defines the experiment objective and presents the results of the preliminary design of the EPICS. The experiment will include testing three subscale self-contained SFE units: one containing baseline components, and two units having variations in key component materials. Tests will be conducted at varying current and thermal condition.

The paper relates the author's experiences in editing and publishing a journal in microfiche, devoted to the future of bibliographic control and related issues. The use of a micro format was dictated by financial considemtions, but it offers additional advantages of speed and flexibility. The first year of publication has provided its editor, a librarian, with a revealing look at journal distribution from the publisher's point of view.