Defining Simulation Intent

Defining Simulation Intent involves capturing high level modelling and idealisation decisions in order to create an efficient and fit-for-purpose analysis. These decisions are recorded as attributes of the decomposed design space.

An approach to defining Simulation Intent is described utilising three known technologies: Cellular Modelling, the subdivision of space into volumes of simulation significance (structures, gas paths, internal and external airflows etc.); Equivalencing, maintaining a consistent and coherent description
of the equivalent representations of the spatial cells in different analysis models; and Virtual Topology, which offers tools for partitioning and de-partitioning the model without disturbing the manufacturing oriented design geometry. The end result is a convenient framework to which high level analysis attributes can be applied, and from which detailed analysis models can be generated
with a high degree of controllability, repeatability and automation. There are multiple novel aspects to the approach, including its reusability, robustness to changes in model topology and the inherent links created between analysis models at different levels of fidelity and physics.

By utilising Simulation Intent, CAD modelling for simulation can be fully exploited and simulation work-flows can be more readily automated, reducing many repetitive manual tasks (e.g. the definition of appropriate coupling between elements of different types and the application of boundary conditions). The approach has been implemented and tested with practical examples, and
significant benefits are demonstrated.

From Francis Hutcheson to James McCosh: Irish Presbyterians and Defining the Scottish Philosophy in the Nineteenth Century

This article examines the disputes amongst Irish Presbyterians about the teaching of moral philosophy by Professor John Ferrie in the college department of the Royal Belfast Academical Institution in the early nineteenth century and the substantive philosophical and theological issues that were raised. These issues have largely been ignored by Irish historians, but a discussion of them is of general relevance to historians of ideas as they illuminate a series of broader questions about the definition and development of Scottish philosophy. These are represented in the move from two philosophers who had strong connections with Irish Presbyterianism—Francis Hutcheson, the early eighteenth-century moral sense philosopher and theological moderate from County Down, and James McCosh, nineteenth-century exponent of modified Common Sense philosophy at Queen's College Belfast and a committed evangelical. In particular, this article addresses three important themes—the definition and character of ‘the Scottish philosophy’, the relationship between evangelicalism and Common Sense philosophy, and the process of development and adaptation that occurred in eighteenth-century Scottish thought during the first half of the nineteenth century.

Defining and assessing animal pain

The detection and assessment of pain in animals is crucial to improving their welfare in a variety of contexts in which humans are ethically or legally bound to do so. Thus clear standards to judge whether pain is likely to occur in any animal species is vital to inform whether to alleviate pain or to drive the refinement of procedures to reduce invasiveness, thereby minimizing pain. We define two key concepts that can be used to evaluate the potential for pain in both invertebrate and vertebrate taxa. First, responses to noxious, potentially painful events should affect neurobiology, physiology and behaviour in a different manner to innocuous stimuli and subsequent behaviour should be modified including avoidance learning and protective responses. Second, animals should show a change in motivational state after experiencing a painful event such that future behavioural decision making is altered and can be measured as a change in conditioned place preference, self-administration of analgesia, paying a cost to access analgesia or avoidance of painful stimuli and reduced performance in concurrent events. The extent to which vertebrate and selected invertebrate groups fulfil these criteria is discussed in light of the empirical evidence and where there are gaps in our knowledge we propose future studies are vital to improve our assessment of pain. This review highlights arguments regarding animal pain and defines criteria that demonstrate, beyond a reasonable doubt, whether animals of a given species experience pain.

Defining the role of common variation in the genomic and biological architecture of adult human height

Using genome-wide data from 253,288 individuals, we identified 697 variants at genome-wide significance that together explained one-fifth of the heritability for adult height. By testing different numbers of variants in independent studies, we show that the most strongly associated 1/42,000, 1/43,700 and 1/49,500 SNPs explained 1/421%, 1/424% and 1/429% of phenotypic variance. Furthermore, all common variants together captured 60% of heritability. The 697 variants clustered in 423 loci were enriched for genes, pathways and tissue types known to be involved in growth and together implicated genes and pathways not highlighted in earlier efforts, such as signaling by fibroblast growth factors, WNT/I 2-catenin and chondroitin sulfate-related genes. We identified several genes and pathways not previously connected with human skeletal growth, including mTOR, osteoglycin and binding of hyaluronic acid. Our results indicate a genetic architecture for human height that is characterized by a very large but finite number (thousands) of causal variants.

Abstract 1905: Defining a therapeutic classification of breast cancer by actionable targets

Breast cancer remains a frequent cause of female cancer death despite the great strides in elucidation of biological subtypes and their reported clinical and prognostic significance. We have defined a general cohort of breast cancers in terms of putative actionable targets, involving growth and proliferative factors, the cell cycle, and apoptotic pathways, both as single biomarkers across a general cohort and within intrinsic molecular subtypes.

We identified 293 patients treated with adjuvant chemotherapy. Additional hormonal therapy and trastuzumab was administered depending on hormonal and HER2 status respectively. We performed immunohistochemistry for ER, PR, HER2, MM1, CK5/6, p53, TOP2A, EGFR, IGF1R, PTEN, p-mTOR and e-cadherin. The cohort was classified into luminal (62%) and non-luminal (38%) tumors as well as luminal A (27%), luminal B HER2 negative (22%) and positive (12%), HER2 enriched (14%) and triple negative (25%). Patients with luminal tumors and co-overexpression of TOP2A or IGF1R loss displayed worse overall survival (p=0.0251 and p=0.0008 respectively). Non-luminal tumors had much greater heterogeneous expression profiles with no individual markers of prognostic significance. Non-luminal tumors were characterised by EGFR and TOP2A overexpression, IGF1R, PTEN and p-mTOR negativity and extreme p53 expression.

Our results indicate that only a minority of intrinsic subtype tumors purely express single novel actionable targets. This lack of pure biomarker expression is particular prevalent in the triple negative subgroup and may allude to the mechanism of targeted therapy inaction and myriad disappointing trial results. Utilising a combinatorial biomarker approach may enhance studies of targeted therapies providing additional information during design and patient selection while also helping decipher negative trial results.

Defining the content and delivery of an intervention to Change AdhereNce to treatment in BonchiEctasis (CAN-BE): a qualitative approach incorporating the Theoretical Domains Framework, behavioural change techniques and stakeholder expert panels

Background
Low patient adherence to treatment is associated with poorer health outcomes in bronchiectasis. We sought to use the Theoretical Domains Framework (TDF) (a framework derived from 33 psychological theories) and behavioural change techniques (BCTs) to define the content of an intervention to change patients’ adherence in bronchiectasis (Stage 1 and 2) and stakeholder expert panels to define its delivery (Stage 3).

Methods
We conducted semi-structured interviews with patients with bronchiectasis about barriers and motivators to adherence to treatment and focus groups or interviews with bronchiectasis healthcare professionals (HCPs) about their ability to change patients’ adherence to treatment. We coded these data to the 12 domain TDF to identify relevant domains for patients and HCPs (Stage 1). Three researchers independently mapped relevant domains for patients and HCPs to a list of 35 BCTs to identify two lists (patient and HCP) of potential BCTs for inclusion (Stage 2). We presented these lists to three expert panels (two with patients and one with HCPs/academics from across the UK). We asked panels who the intervention should target, who should deliver it, at what intensity, in what format and setting, and using which outcome measures (Stage 3).

Results
Eight TDF domains were perceived to influence patients’ and HCPs’ behaviours: Knowledge, Skills, Beliefs about capability, Beliefs about consequences, Motivation, Social influences, Behavioural regulation and Nature of behaviours (Stage 1). Twelve BCTs common to patients and HCPs were included in the intervention: Monitoring, Self-monitoring, Feedback, Action planning, Problem solving, Persuasive communication, Goal/target specified:behaviour/outcome, Information regarding behaviour/outcome, Role play, Social support and Cognitive restructuring (Stage 2). Participants thought that an individualised combination of these BCTs should be delivered to all patients, by a member of staff, over several one-to-one and/or group visits in secondary care. Efficacy should be measured using pulmonary exacerbations, hospital admissions and quality of life (Stage 3).

Conclusions
Twelve BCTs form the intervention content. An individualised selection from these 12 BCTs will be delivered to all patients over several face-to-face visits in secondary care. Future research should focus on developing physical materials to aid delivery of the intervention prior to feasibility and pilot testing. If effective, this intervention may improve adherence and health outcomes for those with bronchiectasis in the future.

Defining Democracy: Voting Procedures in Decision-making, Elections and Governance

Book Review: Emerson, Peter, Defining Democracy: Voting Procedures in Decision-making, Elections and
Governance (2nd edn), Springer, London, 2012,

Defining consensus norms for palliative care of people with intellectual disabilities in Europe using Delphi methods: A White Paper from the European Association of Palliative care

Background: People with intellectual disabilities often present with unique challenges that make it more difficult to meet their
palliative care needs.
Aim: To define consensus norms for palliative care of people with intellectual disabilities in Europe.
Design: Delphi study in four rounds: (1) a taskforce of 12 experts from seven European countries drafted the norms, based on available empirical knowledge and regional/national guidelines; (2) using an online survey, 34 experts from 18 European countries evaluated the draft norms, provided feedback and distributed the survey within their professional networks. Criteria for consensus
were clearly defined; (3) modifications and recommendations were made by the taskforce; and (4) the European Association for
Palliative Care reviewed and approved the final version.
Setting and participants: Taskforce members: identified through international networking strategies. Expert panel: a purposive sample identified through taskforce members’ networks.
Results: A total of 80 experts from 15 European countries evaluated 52 items within the following 13 norms: equity of access, communication, recognising the need for palliative care, assessment of total needs, symptom management, end-of-life decision making, involving those who matter, collaboration, support for family/carers, preparing for death, bereavement support, education/training
and developing/managing services. None of the items scored less than 86% agreement, making a further round unnecessary. In light of respondents’ comments, several items were modified and one item was deleted.
Conclusion: This White Paper presents the first guidance for clinical practice, policy and research related to palliative care for people with intellectual disabilities based on evidence and European consensus, setting a benchmark for changes in policy and practice.

Small Steps or Giant Leaps? Defining Reconciliation in the Transition from Conflict in Northern Ireland

The context of Northern Ireland in the transition of conflict has produced a range of efforts to bring about reconciliation. However, definitions and understandings of the nature of reconciliation differ. This paper draws together how reconciliation has been defined in theory in Northern Ireland and elsewhere, examines some models of practice in the light of that theory and illustrates the process of reconciliation through general initiatives in Northern Ireland and specific projects seeking to reconcile at community level. It is concluded that, while political and public processes can set a context and space for engagement to take place, reconciliation is fundamentally about personal encounter and relationship, which have to take place in a range of settings and at all levels of a society that has experienced conflict.