Epidermal growth factor and transforming growth factor alpha characteristics of human oral carcinoma cell lines.

This study examined the expression of epidermal growth factor (EGF) cell-surface receptors, the response to exogenous ligand and the autocrine production of transforming growth factor alpha (TGF-alpha) in normal and carcinoma-derived human oral keratinocytes. One of eight malignant cell lines overexpressed EGF receptors, while the remainder expressed receptor numbers similar to normal cells. Exogenous EGF stimulated incorporation of tritiated thymidine in a dose-dependent manner. In keratinocytes expressing normal numbers of EGF receptors, the cellular response to exogenous EGF correlated positively with total EGF receptor number. SCC-derived keratinocytes produced more TGF-alpha than normal cells. There was no statistical correlation between the autocrine production of TGF-alpha, EGF cell-surface receptor expression and cellular response to exogenous EGF. While the growth-stimulatory effects of exogenous TGF-alpha were inhibited by the addition of a neutralising antibody, the presence of this antibody in conditioned medium failed to produce a similar decrease in growth. The results indicate that overexpression of EGF receptors is not an invariable characteristic of human oral squamous carcinoma-derived cell lines. Further, the contribution of TGF-alpha to the growth of normal and carcinoma-derived human oral keratinocytes in vitro may be less significant than previously documented

IPCP: Immersive Parallel Coordinates Plots for Engineering Design Processes

Computational engineering design methods and tools are common practice in modern industry. Such approaches are integral in enabling designers to efficiently explore larger and more complex design spaces. However, at the same time, computational engineering design methods tend to dramatically increase the number of candidate solutions that decision-makers must interpret in order to make appropriate choices within a set of solutions. Since all candidate solutions can be represented in digital form together with their assessment criteria, evaluated according to some sort of simulation model, a natural way to explore and understand the complexities of the design problem is to visualize their multidimensional nature. The task now involves the discovery of patterns and trends within the multidimensional design space. In this work, we aim to enhance the design decision-making process by embedding visual analytics into an immersive virtual reality environment. To this end, we present a system called IPCP: immersive parallel coordinates plots. IPCP combines the well-established parallel coordinates visualization technique for high-dimensional data with immersive virtual reality. We propose this approach in order to exploit and discover efficient means to use new technology within a conventional decision-making process. The aim is to provide benefits by enhancing visualizations of 3D geometry and other physical quantities with scientific information. We present the design of this system, which allows the representation and exploration of multidimensional scientific datasets. A qualitative evaluation with two surrogate expert users, knowledgeable in multidimensional data analysis, demonstrate that the system can be used successfully to detect both known and previously unknown patterns in a real-world test dataset, producing an early indicative validation of its suitability for decision support in engineering design processes.Cambridge European and Trinity Hall; Engineering and Physical Sciences Research Council (EPSRC-1788814

Social support for and through exercise and sport in a sample of men with serious mental illness.

Social support is important for people experiencing serious mental illness and is also important during the initiation and maintenance of exercise. In this article we draw on interpretive research into the experiences of 11 men with serious mental illness to explore four dimensions of social support both for and through exercise. Our findings suggest that informational, tangible, esteem, and emotional support were both provided for and given by participants through exercise. We conclude that experiences of both receiving and giving diverse forms of support in this way are significant for some people living with and recovering from serious mental illness

MiMiR - an integrated platform for microarray data sharing, mining and analysis

Background: Despite considerable efforts within the microarray community for standardising data format, content and description, microarray technologies present major challenges in managing, sharing, analysing and re-using the large amount of data generated locally or internationally. Additionally, it is recognised that inconsistent and low quality experimental annotation in public data repositories significantly compromises the re-use of microarray data for meta-analysis. MiMiR, the Microarray data Mining Resource was designed to tackle some of these limitations and challenges. Here we present new software components and enhancements to the original infrastructure that increase accessibility, utility and opportunities for large scale mining of experimental and clinical data.Results: A user friendly Online Annotation Tool allows researchers to submit detailed experimental information via the web at the time of data generation rather than at the time of publication. This ensures the easy access and high accuracy of meta-data collected. Experiments are programmatically built in the MiMiR database from the submitted information and details are systematically curated and further annotated by a team of trained annotators using a new Curation and Annotation Tool. Clinical information can be annotated and coded with a clinical Data Mapping Tool within an appropriate ethical framework. Users can visualise experimental annotation, assess data quality, download and share data via a web-based experiment browser called MiMiR Online. All requests to access data in MiMiR are routed through a sophisticated middleware security layer thereby allowing secure data access and sharing amongst MiMiR registered users prior to publication. Data in MiMiR can be mined and analysed using the integrated EMAAS open source analysis web portal or via export of data and meta-data into Rosetta Resolver data analysis package.Conclusion: The new MiMiR suite of software enables systematic and effective capture of extensive experimental and clinical information with the highest MIAME score, and secure data sharing prior to publication. MiMiR currently contains more than 150 experiments corresponding to over 3000 hybridisations and supports the Microarray Centre's large microarray user community and two international consortia. The MiMiR flexible and scalable hardware and software architecture enables secure warehousing of thousands of datasets, including clinical studies, from microarray and potentially other -omics technologies

Evaluation of MPA designs that protect highly mobile megafauna now and under climate change scenarios

Marine protected area (MPA) designs, including large-scale MPAs (LSMPAs; \u3e150,000 km2), mobile MPAs (fluid spatiotemporal boundaries), and MPA networks, may offer different benefits to species and could enhance protection by encompassing spatiotemporal scales of animal movement. We sought to understand how well LSMPAs could benefit nine highly-mobile marine species in the tropics now and into the future by: 1) evaluating current range overlap within a LSMPA; 2) evaluating range overlap under climate change projections; and 3) evaluating how well theoretical MPA designs benefit these nine species. We focused on Palmyra Atoll and Kingman Reef, a 2000 km2 area within the 1.2 million km2 U.S. Pacific Remote Islands Marine National Monument (PRIMNM) that contains marine megafauna (reef and pelagic fishes; sea turtles; seabirds; cetaceans) reflecting different behaviors and habitat use. Our approach is useful for evaluating the effectiveness of the Palmyra-Kingman MPA and PRIMNM in protecting these species, and tropical LSMPAs in general, and for informing future MPA design. Stationary MPAs provided protection at varying scales. Reef manta rays (Mobula alfredi), grey reef sharks (Carcharhinus amblyrhynchos), green sea turtles (Chelonia mydas), and bottlenose dolphins (Tursiops truncatus) had overall small ranges (\u3c100 km from Palmyra-Kingman) and could benefit from stationary MPAs that contained heterogenous reef habitats. Yellowfin tuna (Thunnus albacares), sooty terns (Onychoprion fuscatus), red-footed boobies (Sula sula), great frigatebirds (Fregata minor), and melon-headed whales (Peponocephala electra) navigated complex oceanographic processes and may benefit most from mobile MPAs that shift with features including thermal fronts, cyclic regions of elevated productivity, and eddies, if relationships with these features are established and predictable. All species had capacity to travel to nearby reef systems, illustrating potential benefits of MPA networks and protected corridors. Suitable habitats will likely contract for all species as warm water expands under climate change scenarios (species habitats were predicted to decrease by 4–49% at Palmyra-Kingman) and MPAs may not protect suitable habitats into the future. Species habitat requirements and movement ecologies are critical aspects of marine spatial planning, especially with respect to dynamic ocean processes and a changing climate

Pre-therapy mRNA expression of TNF is associated with regimen-related gastrointestinal toxicity in patients with esophageal cancer: a pilot study

Author version made available following 12 month embargo from date of publication (27 March 2015) in accordance with publisher copyright policy.Purpose Esophageal cancer has a high mortality rate, and its multimodality treatment is often associated with significant rates of severe toxicity. Effort is needed to uncover ways to maximize effectiveness of therapy through identification of predictive markers of response and toxicity. As such, the aim of this study was to identify genes predictive of chemoradiotherapy-induced gastrointestinal toxicity using an immune pathway-targeted approach. Methods Adults with esophageal cancer treated with chemotherapy consisting of 5-fluorouracil and cisplatin and 45–50 Gy radiation were recruited to the study. Pre-therapy-collected whole blood was analyzed for relative expression of immune genes using real-time polymerase chain reaction (RT-PCR). Gene expression was compared between patients who experienced severe regimen-related gastrointestinal toxicity vs. those experiencing mild to moderate toxicity. Results Blood from 31 patients were analyzed by RT-PCR. Out of 84 immune genes investigated, TNF was significantly elevated (2.05-fold, p = 0.025) in the toxic group (n = 12) compared to the non-toxic group (n = 19). Nausea and vomiting was the most commonly documented severe toxicity. No associations between toxicity and response, age, sex, histology, or treatment were evident. Conclusions This study supports evidence of TNF as a predictive biomarker in regimen-related gastrointestinal toxicity. Confirming these findings in a larger cohort is warranted

Where to Forage When Afraid: Does Perceived Risk Impair Use of the Foodscape?

The availability and quality of forage on the landscape constitute the foodscape within which animals make behavioral decisions to acquire food. Novel changes to the foodscape, such as human disturbance, can alter behavioral decisions that favor avoidance of perceived risk over food acquisition. Although behavioral changes and population declines often coincide with the introduction of human disturbance, the link(s) between behavior and population trajectory are difficult to elucidate. To identify a pathway by which human disturbance may affect ungulate populations, we tested the Behaviorally Mediated Forage‐Loss Hypothesis, wherein behavioral avoidance is predicted to reduce use of available forage adjacent to disturbance. We used GPS collar data collected from migratory mule deer (Odocoileus hemionus) to evaluate habitat selection, movement patterns, and time‐budgeting behavior in response to varying levels of forage availability and human disturbance in three different populations exposed to a gradient of energy development. Subsequently, we linked animal behavior with measured use of forage relative to human disturbance, forage availability, and quality. Mule deer avoided human disturbance at both home range and winter range scales, but showed negligible differences in vigilance rates at the site level. Use of the primary winter forage, sagebrush (Artemisia tridentata), increased as production of new annual growth increased but use decreased with proximity to disturbance. Consequently, avoidance of human disturbance prompted loss of otherwise available forage, resulting in indirect habitat loss that was 4.6‐times greater than direct habitat loss from roads, well pads, and other infrastructure. The multiplicative effects of indirect habitat loss, as mediated by behavior, impaired use of the foodscape by reducing the amount of available forage for mule deer, a consequence of which may be winter ranges that support fewer animals than they did before development

Does biodiversity benefit when the logging stops? An analysis of conservation risks and opportunities in active versus inactive logging concessions in Borneo

The island of Borneo is a biodiversity hotspot of global importance that continues to suffer from one of the highest deforestation rates in the tropics. Selective logging concessions overlay a third of the remaining natural forests in the Indonesian part of Borneo, but many of these concessions have become inactive in recent years. Whereas the cessation of logging could be beneficial to biodiversity, the absence of a logging company's presence in the forest could also leave the concession open to deforestation by other actors. Using remote sensing analyses, we evaluate 1) whether inactive concessions are more likely to suffer from deforestation than active ones, 2) the possible reasons why concessions become inactive, and 3) which inactive concessions hold the most potential for biodiversity conservation, if protected from deforestation. Our analysis shows that, counterintuitively, inactive concessions overall suffer a higher rate of forest loss than active ones. We find that small concession size and high elevation are correlated with inactive status. We identified several inactive concessions that, if maintained as natural forest, could significantly contribute to biodiversity conservation, as exemplified by their importance to two umbrella species: Bornean orangutan (Critically Endangered) and Sunda clouded leopard (Vulnerable). Because timber operations in other tropical regions are likely to experience similar cycles of activity and inactivity, the fate of inactive timber concessions and the opportunities they create for conservation deserve much greater attention from conservation scientists and practitioners

Expert guidance on the multidisciplinary management of cystinosis in adolescent and adult patients

Cystinosis, a rare autosomal recessive lysosomal storage disorder, results in an abnormal accumulation of the amino acid cystine in multiple organs and tissues of the body. Renal symptoms typically develop in the first few months of life, with extra-renal manifestations becoming apparent over the next 10-20 years, which require coordinated multidisciplinary care. Here, we describe a consensus-based guidance to support the management of adolescents and adults living with cystinosis. The programme was led by a Steering Committee (SC) of six experts in the management of patients with cystinosis, who identified a list of 15 key questions reflecting the multi-organ effects of cystinosis. An Extended Faculty (EF) of eight additional specialists was invited to answer the questions via an online digital platform using a quasi-Delphi approach. The consolidated answers were summarized into recommendations. Where evidence was lacking, recommendations were developed using collective expert consensus. The EF was asked to agree/disagree with the clinical recommendations. The expert-agreed clinical recommendations provide guidance that considers both renal and extra-renal systems. The topics covered are advice on fertility and family planning, consideration of the nervous, muscular, ophthalmic, cardio-respiratory, endocrine, dermatological and gastrointestinal systems, as well as guidance on dental care, diet, lifestyle, and improving quality of life and psychological well-being. In summary, this work outlines recommendations and a checklist for clinicians with a vision for improving and standardizing the multidisciplinary care for patients with cystinosis.Peer reviewe