A new in-situ method to estimate fish target strength reveals high variability in broadband measurements

Acknowledgements The authors thank the Greenland Institute of Natural Resources (GINR), the University of Aberdeen, and Marine Alliance for Science and Technology for Scotland (MASTS) for funding this study. MASTS is funded by the Scottish Funding Council (grant no. HR09011) and contributing institutions. Further, they thank GINR for providing access to their facilities.Peer reviewedPublisher PD

Multimodal Literacy in School Science

This book establishes a new theoretical and practical framework for multimodal disciplinary literacy (MDL) fused with the subject-specific science pedagogies of senior high school biology, chemistry and physics. It builds a compatible alignment of multiple representation and representation construction approaches to science pedagogy with the social semiotic, systemic functional linguistic-based approaches to explicit teaching of disciplinary literacy. The early part of the book explicates the transdisciplinary negotiated theoretical underpinning of the MDL framework, followed by the research-informed repertoire of learning experiences that are then articulated into a comprehensive framework of options for the planning of classroom work. Practical adoption and adaptation of the framework in biology, chemistry and physics classrooms are detailed in separate chapters. The latter chapters indicate the impact of the collaborative research on teachers' professional learning and students’ multimodal disciplinary literacy engagement, concluding with proposals for accommodating emerging developments in MDL in an ever-changing digital communication world. The MDL framework is designed to enable teachers to develop all students' disciplinary literacy competencies. This book will be of interest to researchers, teacher educators and postgraduate students in the field of science education. It will also have appeal to those in literacy education and social semiotics

Continuous hyperfractionated accelerated radiotherapy - Escalated dose (CHART-ED): A phase i study

Patients who present with locally advanced inoperable non-small cell lung cancer (NSCLC) may be suitable for radical radiotherapy. A randomised trial of 563 patients compared CHART and conventional radical radiotherapy (60 Gy/30f) given over 6 weeks and suggested that CHART resulted in a 9% improvement in 2-year survival (Saunders et al., 1999). RT dose escalation for both conventional and CHARTWEL (CHART-WeekEndLess) - fractionation schedules is feasible with modern 3-dimensional CT-based planning techniques and we initiated a phase I CHART dose escalation study in 2009. Methods Patients with WHO performance status 0-2 histologically confirmed, inoperable, stage I-III non-small cell lung cancer were recruited into an open phase I dose escalation trial. Three cohorts of six patients were recruited sequentially. Total dose was escalated from standard CHART radiotherapy of 54 Gy/36f/12 days to 57.6 Gy (2 × 1.8 Gy fractions on day 15, Group 1), 61.2 Gy (4 × 1.8 Gy fractions on days 15-16, Group 2) and 64.8 Gy (6 × 1.8 Gy fractions on days 15-17, Group 3). Results Between April 2010 and May 2012, 18 patients were enrolled from 5 UK centres and received escalated dose radiotherapy. 14 were male, 16 squamous cell histology and 12 were stage IIIA or IIIB. The median age was 70 years and baseline characteristics were similar across the three dose cohorts. One patient did not start escalated radiotherapy but all remaining patients completed their planned radiotherapy schedules. Of these 9 patients have died to date with a median survival of 2 years across the three cohorts. Grade 3 or 4 adverse events (fatigue, dysphagia, nausea and anorexia - classified according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.0) were reported in 6 patients but the pre-specified dose limiting toxicities (grade 4 early oesophagitis; grade 3 cardiac, spinal cord and pneumonitis) were not observed. Conclusions CHART remains a radiotherapy schedule in routine use across the UK and in this dose escalation study no dose limiting toxicities were observed. We feel the dose of 64.8 Gy/42f/17 days should be taken forward into further clinical trials. The sample size used in this study was small so we plan a randomised phase II study that includes other radiotherapy schedules to confirm safety and select an accelerated sequential chemo-radiotherapy schedule to take into phase III studies

New invasive Nemertean species (Cephalothrix Simula) in England with high levels of tetrodotoxin and a microbiome linked to toxin metabolism

The marine nemertean Cephalothrix simula originates from the Pacific Ocean but in recent years has been discovered in northern Europe. The species has been associated with high levels of the marine neurotoxin Tetrodotoxin, traditionally associated with Pufferfish Poisoning. This study reports the first discovery of two organisms of C. simula in the UK, showing the geographical extent of this species is wider than originally described. Species identification was initially conducted morphologically, with confirmation by Cox 1 DNA sequencing. 16S gene sequencing enabled the taxonomic assignment of the microbiome, showing the prevalence of a large number of bacterial genera previously associated with TTX production including Alteromonas, Vibrio and Pseudomonas. LC-MS/MS analysis of the nemertean tissue revealed the presence of multiple analogues of TTX, dominated by the parent TTX, with a total toxin concentration quantified at 54 µg TTX per g of tissue. Pseudomonas luteola isolated from C. simula, together with Vibrio alginolyticus from the native nemertean Tubulanus annulatus, were cultured at low temperature and both found to contain TTX. Overall, this paper confirms the high toxicity of a newly discovered invasive nemertean species with links to toxin-producing marine bacteria and the potential risk to human safety. Further work is required to assess the geographical extent and toxicity range of C. simula along the UK coast in order to properly gauge the potential impacts on the environment and human safety

PARC:a phase I/II study evaluating the safety and activity of pegylated recombinant human arginase BCT-100 in relapsed/refractory cancers of children and young adults

Background: The survival for many children with relapsed/refractory cancers remains poor despite advances in therapies. Arginine metabolism plays a key role in the pathophysiology of a number of pediatric cancers. We report the first in child study of a recombinant human arginase, BCT-100, in children with relapsed/refractory hematological, solid or CNS cancers.Procedure: PARC was a single arm, Phase I/II, international, open label study. BCT-100 was given intravenously over one hour at weekly intervals. The Phase I section utilized a modified 3 + 3 design where escalation/de-escalation was based on both the safety profile and the complete depletion of arginine (defined as adequate arginine depletion; AAD <8μM arginine in the blood after 4 doses of BCT-100). The Phase II section was designed to further evaluate the clinical activity of BCT-100 at the pediatric RP2D determined in the Phase I section, by recruitment of patients with pediatric cancers into 4 individual groups. A primary evaluation of response was conducted at eight weeks with patients continuing to receive treatment until disease progression or unacceptable toxicity.Results: 49 children were recruited globally. The Phase I cohort of the trial established the Recommended Phase II Dose of 1600U/kg iv weekly in children, matching that of adults. BCT-100 was very well tolerated. No responses defined as a CR, CRi or PR were seen in any cohort within the defined 8 week primary evaluation period. However a number of these relapsed/refractory patients experienced prolonged radiological SD.Conclusion: Arginine depletion is a clinically safe and achievable strategy in children with cancer. The RP2D of BCT-100 in children with relapsed/refractory cancers is established at 1600U/kg intravenously weekly and can lead to sustained disease stability in this hard to treat population.Clinical trial registration: EudraCT, 2017-002762-44; ISRCTN, 21727048; and ClinicalTrials.gov, NCT03455140

Rust expression browser: an open source database for simultaneous analysis of host and pathogen gene expression profiles with expVIP

BackgroundTranscriptomics is being increasingly applied to generate new insight into the interactions between plants and their pathogens. For the wheat yellow (stripe) rust pathogen (Puccinia striiformis f. sp. tritici, Pst) RNA-based sequencing (RNA-Seq) has proved particularly valuable, overcoming the barriers associated with its obligate biotrophic nature. This includes the application of RNA-Seq approaches to study Pst and wheat gene expression dynamics over time and the Pst population composition through the use of a novel RNA-Seq based surveillance approach called "field pathogenomics". As a dual RNA-Seq approach, the field pathogenomics technique also provides gene expression data from the host, giving new insight into host responses. However, this has created a wealth of data for interrogation.ResultsHere, we used the field pathogenomics approach to generate 538 new RNA-Seq datasets from Pst-infected field wheat samples, doubling the amount of transcriptomics data available for this important pathosystem. We then analysed these datasets alongside 66 RNA-Seq datasets from four Pst infection time-courses and 420 Pst-infected plant field and laboratory samples that were publicly available. A database of gene expression values for Pst and wheat was generated for each of these 1024 RNA-Seq datasets and incorporated into the development of the rust expression browser (http://www.rust-expression.com). This enables for the first time simultaneous 'point-and-click' access to gene expression profiles for Pst and its wheat host and represents the largest database of processed RNA-Seq datasets available for any of the three Puccinia wheat rust pathogens. We also demonstrated the utility of the browser through investigation of expression of putative Pst virulence genes over time and examined the host plants response to Pst infection.ConclusionsThe rust expression browser offers immense value to the wider community, facilitating data sharing and transparency and the underlying database can be continually expanded as more datasets become publicly available

Characterization of the genomic features and expressed fusion genes in micropapillary carcinomas of the breast

Micropapillary carcinoma ( MPC ) is a rare histological special type of breast cancer, characterized by an aggressive clinical behaviour and a pattern of copy number aberrations ( CNAs ) distinct from that of grade‐ and oestrogen receptor ( ER )‐matched invasive carcinomas of no special type ( IC‐NSTs ). The aims of this study were to determine whether MPCs are underpinned by a recurrent fusion gene(s) or mutations in 273 genes recurrently mutated in breast cancer. Sixteen MPCs were subjected to microarray‐based comparative genomic hybridization ( aCGH ) analysis and Sequenom OncoCarta mutation analysis. Eight and five MPCs were subjected to targeted capture and RNA sequencing, respectively. aCGH analysis confirmed our previous observations about the repertoire of CNAs of MPCs . Sequencing analysis revealed a spectrum of mutations similar to those of luminal B IC‐NSTs , and recurrent mutations affecting mitogen‐activated protein kinase family genes and NBPF10 . RNA ‐sequencing analysis identified 17 high‐confidence fusion genes, eight of which were validated and two of which were in‐frame. No recurrent fusions were identified in an independent series of MPCs and IC‐NSTs . Forced expression of in‐frame fusion genes ( SLC2A1–FAF1 and BCAS4–AURKA ) resulted in increased viability of breast cancer cells. In addition, genomic disruption of CDK12 caused by out‐of‐frame rearrangements was found in one MPC and in 13% of HER2 ‐positive breast cancers, identified through a re‐analysis of publicly available massively parallel sequencing data. In vitro analyses revealed that CDK12 gene disruption results in sensitivity to PARP inhibition, and forced expression of wild‐type CDK12 in a CDK12 ‐null cell line model resulted in relative resistance to PARP inhibition. Our findings demonstrate that MPCs are neither defined by highly recurrent mutations in the 273 genes tested, nor underpinned by a recurrent fusion gene. Although seemingly private genetic events, some of the fusion transcripts found in MPCs may play a role in maintenance of a malignant phenotype and potentially offer therapeutic opportunities. © 2014 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/106752/1/path4325.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/106752/2/path4325-sup-0001-AppendixS1.pd