NELFE-Dependent MYC Signature Identifies a Unique Cancer Subtype in Hepatocellular Carcinoma.

The MYC oncogene is dysregulated in approximately 30% of liver cancer. In an effort to exploit MYC as a therapeutic target, including in hepatocellular carcinoma (HCC), strategies have been developed on the basis of MYC amplification or gene translocation. Due to the failure of these strategies to provide accurate diagnostics and prognostic value, we have developed a Negative Elongation Factor E (NELFE)-Dependent MYC Target (NDMT) gene signature. This signature, which consists of genes regulated by MYC and NELFE, an RNA binding protein that enhances MYC-induced hepatocarcinogenesis, is predictive of NELFE/MYC-driven tumors that would otherwise not be identified by gene amplification or translocation alone. We demonstrate the utility of the NDMT gene signature to predict a unique subtype of HCC, which is associated with a poor prognosis in three independent cohorts encompassing diverse etiologies, demographics, and viral status. The application of gene signatures, such as the NDMT signature, offers patients access to personalized risk assessments, which may be utilized to direct future care

Abrupt thermal transition reveals hydrothermal boundary and role of seamounts within the Cocos Plate

New thermal data from 18–24 Ma lithosphere on the Cocos Plate delineate contrasting subsurface thermal conditions in adjacent sections of crust. Heat flow through seafloor created at the East Pacific Rise is generally suppressed by ~70% relative to conductive lithospheric cooling models, whereas heat flow through adjacent, similarly-aged lithosphere generated at the Cocos-Nazca Spreading Center is consistent with these models. The transition between thermal regimes is remarkably abrupt, only 2–5 km wide, indicating a shallow hydrothermal origin. The transition is more closely associated with differences in the distribution of basement outcrops than with tectonic boundaries, demonstrating the importance of the former in extracting heat from the lithosphere on a regional basis

Designing a consequentially based study into the online support of pre-service teachers in the UK

This paper reports on the design of a pilot doctoral study into the online support of pre-service teachers. It highlights the significance of a consequential, rather than deontological, perspective in guiding the development of a study's design. The study initially aimed to explore pre-service teachers’ perceptions and use of social media on their school placements by setting up groups on Facebook and Twitter. However, several problems occurred in relation to the recruitment of participants. It became increasingly clear that there was significance in the positionality of the researcher as an “outsider” to the research context and the potential role for gatekeepers in understanding remote research sites. An ethical framework was used to make a more comprehensive analysis of the issues at play, which helped identify ways of proceeding. A redesign of the study followed with a stronger rationale for the way consequential considerations can help address deontological concerns

Assessing Kidney Transplantation Using ECMO-Supported Donors Within a KDPI-Based Allocation System

Background. Organ donors supported by extracorporeal membrane oxygenation (ECMO) have historically been considered high-risk and are judiciously utilized. This study examines transplant outcomes using renal allografts from donors supported on ECMO for nondonation purposes. Methods. Retrospective review of the Gift of Life (Pennsylvania, New Jersey, Delaware) organ procurement organization database, cross-referenced to the Organ Procurement and Transplantation Network database, assessed kidney transplants using donors supported on venoarterial (VA) and venovenous (VV) ECMO for nondonation purposes. Transplants using VA- and VV-ECMO donors were compared with Kidney Donor Profile Index (KDPI)-stratified non-ECMO donors. Regression modeling of the entire ECMO and non-ECMO populations assessed ECMO as predictive of graft survival. Additional regression of the ECMO population alone assessed for donor features associated with graft survival. Results. Seventy-eight ECMO donors yielded 128 kidney transplants (VA: 80, VV: 48). Comparing outcomes using these donors to kidney transplants using organs from KDPI-stratified non-ECMO donors, VA- and VV-ECMO donor grafts conferred similar rates of delayed graft function and posttransplant renal function to KDPI-matched non-ECMO counterparts. VA-ECMO kidneys demonstrated superior graft survival compared with the lowest-quality (KDPI 86%–100%) non-ECMO kidneys and similar graft survival to KDPI \u3c85% non-ECMO kidneys. VV-ECMO showed inferior graft survival to all but the lowest-quality (KDPI 86%–100%) non-ECMO kidneys. VV-ECMO, but not VA-ECMO, was associated with increased risk of graft loss on multivariable regression (hazard ratios—VA: 1.02, VV: 2.18). Higher KDPI, advanced age, increased body mass index, hypertension, and diabetes were identified as high-risk features of ECMO donors. Conclusions. Kidney transplantation using appropriately selected ECMO donors can safely expand the donor pool. Ongoing studies are necessary to determine best practice patterns using kidneys from these donors

Customising virtual globe tours to enhance community awareness of local landscape benefits

Our wellbeing depends upon the services provided by ecosystems and their components. Despite recent advances in academic understanding of ecosystem services, and consideration in UK national environmental policy, a greater awareness is needed at community and individual levels. Dynamic features of virtual globe applications have considerable potential for helping convey the multi-dimensional context of ecosystem services and promoting general awareness. In a case study targeting residents in a small urban fringe river catchment in Norfolk, UK, representatives from local authorities and responsible agencies collaborated with scientists to produce extensive customisation of virtual globes in this context. By implementing a virtual flight over the catchment, different views and scales are traversed to set the context for landscape features and ecosystem services. Characteristic sites, e.g. supplying cultural services, are displayed and relationships with the natural environment are explained using linked on-screen text. Implementation is cost-effective and described for practitioners in ecosystem and landscape management, who may be inexperienced in landscape visualisation. Supplied as three pre-packaged virtual tours, products are made available for download and are publicised at a variety of engagement events, including teaching events with schoolchildren. The tours have attracted public interest and generated positive feedback about improving knowledge of local natural assets. Schoolchildren show confidence with the interface, but supplementary problem-based activities can improve learning opportunities. The capacity of virtual globes to support more participatory involvement of the public in local ecosystem management may increase in the future, but such visualisations can already help promote community awareness of local landscape benefits

Scaffolding school students’ scientific argumentation in inquiry-based learning with evidence maps

This chapter reports a research work investigating the potential of Evidence-based Dialogue Mapping to scaffold young teenagers’ scientific argumentation. Our research objective is to better understand students’ usage of dialogue maps created in Compendium to write scientific explanations in inquiry based learning projects. The participants were 20 students, 12–13 years old, in a summer science course for “gifted and talented” children in the UK. Through qualitative analysis of three case studies, we investigate the value of dialogue mapping as a mediating tool in the scientific reasoning process during a set of inquiry-based learning activities. These activities were published in an online learning environment to foster collaborative learning. Students mapped their discussions in pairs, shared maps via the online forum and in plenary discussions, and wrote essays based on their dialogue maps. This study draws on these multiple data sources: students’ maps in Compendium, writings in science and reflective comments about the uses of mapping for writing. Our analysis highlights the diversity of ways, both successful and unsuccessful, in which dialogue mapping was used by these young teenagers. It also presents future work on knowledge maps for social personal and open environments by including examples from the OpenLearn, weSPOT and ENGAGE projects