Virtual Research Integration Collaboration: Procedural report

The aim of the project is to build a framework for the integration of basic science and clinical research to manage research lifecycles and allow for integration of scientific approaches throughout these lifecycles into the everyday work practice of the consortia that manage translational clinical research. The project will take the CORE VRE and embed it into a National centre for surgical excellence, the Royal National Orthopaedic Hospital (RNOH). The VRE will integrate both with the institutional systems and research life cycle, and with the national systems such as the National Health Service (NHS). It is our aim to integrate the CORE VRE with myExperiment to provide a set of services at RNOH to cover the four main areas of the research cycle, namely: the monitoring and governance of trials (experiment research administration); the trial protocols (experiment workflows); the publishing, dissemination and discussion on the results of trials in a repository; and the discovery of information from the repository and other resources. For this community, there are three tightly coupled areas of focus: research, clinical practice, and education (in the form of continuing professional development and training of the next generation of surgeons). In this project, our user community will be heavily involved in co-designing and codeployment of the tool set, and in particular the front end of the workbench will be user focused. The tools will need to be available to staff anywhere with the organisation, as clinicians need to be able to enter the data during clinics and directors of research need to be able to monitor the trials. This will bring with it a number of inter-operability issues, as we move data between the VRE, the hospital systems (NHS) and the institutional systems. To aid the understanding of the how the system will be used, we outline a typical ‘research cycle’ that includes the practice of a clinical specialist in orthopaedics (who may also be a Higher surgical trainee) and a basic scientist. The purpose of this is to identify time essential information provision and interaction with pervasive technologies. For new researchers one of the most difficult tasks is to learn good practice or find related experiments to learn how to instantiate the protocols; in many organisations it is often easier to repeat an experiment than to find the results of a similar previous experiment. In this abstracted model of the research lifecycle, we have split up the cycle into four main research activities. In each of these activities the different issues and stakeholders are addressed. The wider community nationally is represented by the Musculoskeletal network of Greater London, NHS, e-science, Surgical and VRE communities. It is through the Musculoskeletal network of Greater London that we will be able to co-ordinate knowledge and demonstrations to advise the community and for continuity. This project will impact on the wider academic community in the UK, initially through dissemination via organisations such as BriteNet (Tissue Engineering), The British Orthopaedic Association, British Orthopaedic Research Society, and the British Elbow and Shoulder Society as the groups tied into the consortia development

Predator versus Prey:Locust Looming-Detector Neuron and Behavioural Responses to Stimuli Representing Attacking Bird Predators

Many arthropods possess escape-triggering neural mechanisms that help them evade predators. These mechanisms are important neuroethological models, but they are rarely investigated using predator-like stimuli because there is often insufficient information on real predator attacks. Locusts possess uniquely identifiable visual neurons (the descending contralateral movement detectors, DCMDs) that are well-studied looming motion detectors. The DCMDs trigger ‘glides’ in flying locusts, which are hypothesised to be appropriate last-ditch responses to the looms of avian predators. To date it has not been possible to study glides in response to stimuli simulating bird attacks because such attacks have not been characterised. We analyse video of wild black kites attacking flying locusts, and estimate kite attack speeds of 10.8±1.4 m/s. We estimate that the loom of a kite’s thorax towards a locust at these speeds should be characterised by a relatively low ratio of half size to speed (l/|v|) in the range 4–17 ms. Peak DCMD spike rate and gliding response occurrence are known to increase as l/|v| decreases for simple looming shapes. Using simulated looming discs, we investigate these trends and show that both DCMD and behavioural responses are strong to stimuli with kite-like l/|v| ratios. Adding wings to looming discs to produce a more realistic stimulus shape did not disrupt the overall relationships of DCMD and gliding occurrence to stimulus l/|v|. However, adding wings to looming discs did slightly reduce high frequency DCMD spike rates in the final stages of object approach, and slightly delay glide initiation. Looming discs with or without wings triggered glides closer to the time of collision as l/|v| declined, and relatively infrequently before collision at very low l/|v|. However, the performance of this system is in line with expectations for a last-ditch escape response

Isochromosome 12p formation regulates vitamin D metabolism in testicular cancer

Isochromosome 12p (iChr12p) is typical in almost all invasive testicular cancers. Increased copy number of genes on 12p is associated with the development of a clinically manifest tumor; however, the causative genes have not yet been identified. Chromosome 12 harbors many genes involved in Vitamin D metabolism. RNAseq analysis of Vitamin D receptor (VDR) genes from the TCGA cohort revealed that clustering of VDR expression signatures could differentiate between pure seminomas and non-seminomatous germ cell tumors (NSGCT). Using TCGA mRNA expression of anabolic (CYP2R1, CYP27A1 and CYP27B1) and catabolic (CYP24A1) Vitamin D enzymes, positive (PTHLH, IFNG, and TNF) and negative (FGF23) feedback regulators could also clearly distinguish between pure seminomas and NSGCT. We hypothesize that the regulation of Vitamin D metabolism might be disturbed through iChr12p formation, influencing testicular carcinogenesis via increased FGF23 and PTHLH expression. While FGF23 represses CYP27B1 and activates catabolism of active hormone, increased PTHLH secretion can lead to hypercalcemia via inactivation of VDR. In conclusion, testicular cancer is associated with extensive modifications in intratesticular Vitamin D homeostasis. Further research is needed to clarify whether Vitamin D deficiency causes the formation of iChr12p and whether Vitamin D deficiency via iChr12p genomic aberration is involved in testicular carcinogenesis

A modified model for the Lobula Giant Movement Detector and its FPGA implementation

The Lobula Giant Movement Detector (LGMD) is a wide-field visual neuron located in the Lobula layer of the Locust nervous system. The LGMD increases its firing rate in response to both the velocity of an approaching object and the proximity of this object. It has been found that it can respond to looming stimuli very quickly and trigger avoidance reactions. It has been successfully applied in visual collision avoidance systems for vehicles and robots. This paper introduces a modified neural model for LGMD that provides additional depth direction information for the movement. The proposed model retains the simplicity of the previous model by adding only a few new cells. It has been simplified and implemented on a Field Programmable Gate Array (FPGA), taking advantage of the inherent parallelism exhibited by the LGMD, and tested on real-time video streams. Experimental results demonstrate the effectiveness as a fast motion detector

Catch before a fall – an iPad application for Osteoporosis Risk Assessment

The Virtual Research Integration Collaboration (VRIC) project provides a framework for the integration of basic science and clinical research. It enables the management of research lifecycles by integrating scientific approaches with everyday work practice in a virtual research environment (VRE). “Catch Before a Fall” (CBaF) is a clinical research project using VRIC. CBaF is aimed at calculating patients’ risk factor of developing osteoporosis and of having an osteoporosis related fracture within the next 10 years. Patients’ data are collected through CBaF and stored in data structures that match the VRIC architecture for automatic importing via a script written for that purpose. Data analysis is conducted in VRIC and the conclusion of the research process is followed up within that tool. In this paper, we describe how CBaF was designed to follow the VRIC framework, and discuss the technical development work of the application

The next generation internet initiative

Digital transformation is pushing all market sectors to level up their digital capabilities to better serve customers and improve the user experience. The European Commission launched in 2016 the Next Generation Internet (NGI) initiative as part of the DSM strategy. NGI includes a number of different – but always interrelated – emerging technologies in the following focus areas: artificial intelligence and autonomous machines, blockchains and distributed ledgers, big data, Internet of Things, 5G, cybersecurity and privacy technologies, cloud and edge computing, and open data. As for cooperation in the field of Information and Communications Technology, Europe and the United States should seek a joint framework to expand efforts in new emerging technologies, while preserving common principles around a comprehensive EU–US digital economy dialogue. The NGI Initiative is an important opportunity to radically rethink the way the Internet works today, and more human-focused narratives are needed more than ever

Recent advances in understanding and managing postoperative respiratory problems [version 1; referees: 2 approved]

Postoperative respiratory complications increase healthcare utilization (e.g. hospital length of stay, unplanned admission to intensive care or high-dependency units, and hospital readmission), mortality, and adverse discharge to a nursing home. Furthermore, they are associated with significant costs. Center-specific treatment guidelines may reduce risks and can be guided by a local champion with multidisciplinary involvement. Patients should be risk-stratified before surgery and offered anesthetic choices (such as regional anesthesia). It is established that laparoscopic surgery improves respiratory outcomes over open surgery but requires tailored anesthesia/ventilation strategies (positive end-expiratory pressure utilization and low inflation pressure). Interventions to optimize treatment include judicious use of intensive care, moderately restrictive fluid therapy, and appropriate neuromuscular blockade with adequate reversal. Patients’ ventilatory drive should be kept within a normal range wherever possible. High-dose opioids should be avoided, while volatile anesthetics appear to be lung protective. Tracheal extubation should occur in the reverse Trendelenburg position, and postoperative continuous positive airway pressure helps prevent airway collapse. In combination, all of these interventions facilitate early mobilization

A p38MAPK/MK2 signaling pathway leading to redox stress, cell death and ischemia/reperfusion injury

Background Many diseases and pathological conditions are characterized by transient or constitutive overproduction of reactive oxygen species (ROS). ROS are causal for ischemia/reperfusion (IR)-associated tissue injury (IRI), a major contributor to organ dysfunction or failure. Preventing IRI with antioxidants failed in the clinic, most likely due to the difficulty to timely and efficiently target them to the site of ROS production and action. IR is also characterized by changes in the activity of intracellular signaling molecules including the stress kinase p38MAPK. While ROS can cause the activation of p38MAPK, we recently obtained in vitro evidence that p38MAPK activation is responsible for elevated mitochondrial ROS levels, thus suggesting a role for p38MAPK upstream of ROS and their damaging effects.<p></p> Results Here we identified p38MAPKα as the predominantly expressed isoform in HL-1 cardiomyocytes and siRNA-mediated knockdown demonstrated the pro-oxidant role of p38MAPKα signaling. Moreover, the knockout of the p38MAPK effector MAPKAP kinase 2 (MK2) reproduced the effect of inhibiting or knocking down p38MAPK. To translate these findings into a setting closer to the clinic a stringent kidney clamping model was used. p38MAPK activity increased upon reperfusion and p38MAPK inhibition by the inhibitor BIRB796 almost completely prevented severe functional impairment caused by IR. Histological and molecular analyses showed that protection resulted from decreased redox stress and apoptotic cell death.<p></p> Conclusions These data highlight a novel and important mechanism for p38MAPK to cause IRI and suggest it as a potential therapeutic target for prevention of tissue injury.<p></p&gt

Enabling the Participation of People with Parkinson's and Their Caregivers in Co-Inquiry around Collectivist Health Technologies

While user participation is central to HCI, co-inquiry takes this further by having participants direct and control research from conceptualisation to completion. We describe a co-inquiry, conducted over 16 months with a Parkinson's support group. We explored how the participation of members might be enabled across multiple stages of a research project, from the generation of research questions to the development of a prototype. Participants directed the research into developing alternative modes of information provision, resulting in ‘Parkinson’s Radio’ — a collectivist health information service produced and edited by members of the support group. We reflect on how we supported participation at different stages of the project and the successes and challenges faced by the team. We contribute insights into the design of collectivist health technologies for this group, and discuss opportunities and tensions for conducting co-inquiry in HCI research