Grid infrastructures supporting paediatric endocrinology across Europe

Paediatric endocrinology is a highly specialised area of clinical medicine with many experts with specific knowledge distributed over a wide geographical area. The European Society for Paediatric Endocrinology (ESPE) is an example of such a body of experts that require regular collaboration and sharing of data and knowledge. This paper describes work, developed as a corollary to the VOTES project [1] and implementing similar architectures, to provide a data grid that allows information to be efficiently distributed between collaborating partners, and also allows wide-scale analyses to be run over the entire data-set, which necessarily involves crossing domain boundaries and negotiating data access between administrations that only trust each other to a limited degree

Modulation of Synaptic Amplification in Sympathetic Ganglia

The purpose of this dissertation was to assess synaptic integration in neurons from the rat superior cervical ganglion (SCG) using complex temporal patterns of virtual synaptic activity that mimic in vivo conditions. The SCG is a paravertebral ganglion that innervates different targets in the head. One of its important roles is to regulate vascular tone. Previous reports have concluded that SCG neurons behave as simple relays between preganglionic synaptic activity from the spinal cord and postganglionic control of end organs. We have tested the hypotheses that (1) postganglionic convergence of strong and weak nicotinic synapses produces variable synaptic amplification in SCG neurons; (2) entrainment of preganglionic activity to the cardiac cycle through arterial baroreceptors increases synaptic gain; (3) the contribution of weak nicotinic synapses to postganglionic integration has been underestimated in vivo due to membrane damage caused by sharp microelectrodes; and (4) angiotensin II (AngII) acts postsynaptically to increase ganglionic synaptic amplification. The approach to creating virtual synapses relied on dynamic clamp. Using whole-cell recordings of SCG neurons in short-term cultures, we found evidence for activity dependent synaptic gain and for the enhancement of gain by cardiac entrainment. Based on this approach, a computational model was developed to simulate human data – this showed that the statistics of human firing patterns could be accounted for by a model that includes secondary synapses and synaptic amplification. Cellular damage was simulated with dynamic clamp by implementing a non-depolarizing shunt conductance. This revealed that damage introduced by microelectrode recordings transformed the intrinsic firing properties of sympathetic neurons and obscured the contribution of weak nicotinic synapses to synaptic gain. Finally, G-protein coupled receptors for AngII increased postganglionic excitability, which facilitated the integration of weak synaptic activity and enhanced synaptic gain. These results have implications for understanding human blood pressure regulation during exercise and hypertension. Until now, the SCG had been discounted as a regulator of blood pressure. Data in this thesis supports an integrative role for synaptic convergence in sympathetic ganglia and the modulation of gain by AngII. These results suggest that future efforts to control blood pressure and treat hypertension could target ganglionic mechanisms

Sifu - a cybersecurity awareness platform with challenge assessment and intelligent coach

Software vulnerabilities, when actively exploited by malicious parties, can lead to catastrophic consequences. Proper handling of software vulnerabilities is essential in the industrial context, particularly when the software is deployed in critical infrastructures. Therefore, several industrial standards mandate secure coding guidelines and industrial software developers’ training, as software quality is a significant contributor to secure software. CyberSecurity Challenges (CSC) form a method that combines serious game techniques with cybersecurity and secure coding guidelines to raise secure coding awareness of software developers in the industry. These cybersecurity awareness events have been used with success in industrial environments. However, until now, these coached events took place on-site. In the present work, we briefly introduce cybersecurity challenges and propose a novel platform that allows these events to take place online. The introduced cybersecurity awareness platform, which the authors call Sifu, performs automatic assessment of challenges in compliance to secure coding guidelines, and uses an artificial intelligence method to provide players with solution-guiding hints. Furthermore, due to its characteristics, the Sifu platform allows for remote (online) learning, in times of social distancing. The CyberSecurity Challenges events based on the Sifu platform were evaluated during four online real-life CSC events. We report on three surveys showing that the Sifu platform’s CSC events are adequate to raise industry software developers awareness on secure coding.info:eu-repo/semantics/publishedVersio

Supporting the clinical trial recruitment process through the grid

Patient recruitment for clinical trials and studies is a large-scale task. To test a given drug for example, it is desirable that as large a pool of suitable candidates is used as possible to support reliable assessment of often moderate effects of the drugs. To make such a recruitment campaign successful, it is necessary to efficiently target the petitioning of these potential subjects. Because of the necessarily large numbers involved in such campaigns, this is a problem that naturally lends itself to the paradigm of Grid technology. However the accumulation and linkage of data sets across clinical domain boundaries poses challenges due to the sensitivity of the data involved that are atypical of other Grid domains. This includes handling the privacy and integrity of data, and importantly the process by which data can be collected and used, and ensuring for example that patient involvement and consent is dealt with appropriately throughout the clinical trials process. This paper describes a Grid infrastructure developed as part of the MRC funded VOTES project (Virtual Organisations for Trials and Epidemiological Studies) at the National e-Science Centre in Glasgow that supports these processes and the different security requirements specific to this domain

Teamwork in Extreme Environments

Teams are relied upon in extreme and challenging environments in which there are considerable demands and failures can have severe consequences. Despite an increased interest in extreme teams, empirical research remains limited. Moreover, whilst the literature differentiates between extreme and non-extreme teams, it rarely distinguishes between different types of extreme teams. In this thesis, I argue extreme teams can be differentiated into multi-team systems (MTS) and teams in isolated, confined environments (ICE). I draw on contextual challenges present in different types of extreme environments to examine what factors support teamwork in emergency response teams (MTS) and expedition teams (ICE). In doing so, I identify methodological and analytical approaches suitable for researching extreme teams (Chapter II and V). MTS often form quickly in the response to emergencies. This creates challenges in establishing communication channels and managing conflicting objectives across inter-agency partners who may have limited experience working with one another. To address these challenges, I explored how teams communicated and coordinated in crises and if this is influenced by team member familiarity. Data were collected from immersive simulations with commanders in the emergency services and students. Mixed methods analysis showed how team processes changed across time (Chapter III) and how familiarity (Chapter IV) alleviated some of the challenges of working in MTS. In contrast to MTS, teams in ICE co-exist for pro-longed periods in hostile and remote settings. This creates challenges in maintaining team cohesion and balancing the personalities and characteristics of isolated individuals for pro-longed periods. Here, I used a diary methodology to track changes in cohesion over time and explore if fluctuations in cohesion are predicted by day-to-day events and the personality composition of teams (Chapter V). Theoretical implications for the importance of context in shaping team behaviours and practical implications for teams operating in extreme environments are provided

Secure, reliable and dynamic access to distributed clinical data

An abundance of statistical and scientific data exists in the area of clinical and epidemiological studies. Much of this data is distributed across regional, national and international boundaries with different policies on access and usage, and a multitude of different schemata for the data often complicated by the variety of supporting clinical coding schemes. This prevents the wide scale collation and analysis of such data as is often needed to infer clinical outcomes and to determine the often moderate effect of drugs. Through grid technologies it is possible to overcome the barriers introduced by distribution of heterogeneous data and services. However reliability, dynamicity and fine-grained security are essential in this domain, and are not typically offered by current grids. The MRC funded VOTES project (Virtual Organisations for Trials and Epidemiological Studies) has implemented a prototype infrastructure specifically designed to meet these challenges. This paper describes this on-going implementation effort and the lessons learned in building grid frameworks for and within a clinical environment

Supporting UK-wide e-clinical trials and studies

As clinical trials and epidemiological studies become increasingly large, covering wider (national) geographical areas and involving ever broader populations, the need to provide an information management infrastructure that can support such endeavours is essential. A wealth of clinical data now exists at varying levels of care (primary care, secondary care, etc.). Simple, secure access to such data would greatly benefit the key processes involved in clinical trials and epidemiological studies: patient recruitment, data collection and study management. The Grid paradigm provides one model for seamless access to such data and support of these processes. The VOTES project (Virtual Organisations for Trials and Epidemiological Studies) is a collaboration between several UK institutions to implement a generic framework that effectively leverages the available health-care information across the UK to support more efficient gathering and processing of trial information. The structure of the information available in the health-care domain in the UK itself varies broadly in-line with the national boundaries of the constituent states (England, Scotland, Wales and Northern Ireland). Technologies must address these political boundaries and the impact these boundaries have in terms of for example, information governance, policies, and of course large-scale heterogeneous distribution of the data sets themselves. This paper outlines the methodology in implementing the framework between three specific data sources that serve as useful case studies: Scottish data from the Scottish Care Information (SCI) Store data repository, data on the General Practice Research Database (GPRD) diabetes trial at Imperial College London, and benign prostate hypoplasia (BPH) data from the University of Nottingham. The design, implementation and wider research issues are discussed along with the technological challenges encountered in the project in the application of Grid technologies