System Evolution, Feedback and Compliant Architectures

Proceedings, International Workshop on Feedback and Evolution in Software and Business Processes (FEAST 2000), Imperial College, London. Supported by EPSRCPostprintNon peer reviewe

Instances and connectors : issues for a second generation process language

This work is supported by UK EPSRC grants GR/L34433 and GR/L32699Over the past decade a variety of process languages have been defined, used and evaluated. It is now possible to consider second generation languages based on this experience. Rather than develop a second generation wish list this position paper explores two issues: instances and connectors. Instances relate to the relationship between a process model as a description and the, possibly multiple, enacting instances which are created from it. Connectors refers to the issue of concurrency control and achieving a higher level of abstraction in how parts of a model interact. We believe that these issues are key to developing systems which can effectively support business processes, and that they have not received sufficient attention within the process modelling community. Through exploring these issues we also illustrate our approach to designing a second generation process language.Postprin

An active-architecture approach to COTS integration

Commercial off-the-shelf (COTS) software products are increasingly used as standard components within integrated information systems. This creates challenges since both their developers and source code are not usually available, and the ongoing development of COTS cannot be predicted. The ArchWare Framework approach recognises COTS products as part of the ambient environment of an information system and therefore an important part of development is incorporating COTS as effective system components. This integration of COTS components, and the composition of components, is captured by an active architecture model which changes as the system evolves. Indeed the architecture modelling language used enables it to express the monitoring and evolution of a system. This active architecture model is structured using control system principles. By modelling both integration and evolution it can guide the system’s response to both predicted and emergent changes that arise from the use of COTS products.Publisher PDFPeer reviewe

CD8 T-cell responses against the immunodominant Theileria parvapeptide Tp249-59 are composed of two distinct populations specific for overlapping 11-mer and 10-mer epitopes

Immunity against Theileria parva is associated with CD8 T-cell responses that exhibit immunodominance, focusing the response against limited numbers of epitopes. As candidates for inclusion in vaccines, characterization of responses against immunodominant epitopes is a key component in novel vaccine development. We have previously demonstrated that the Tp249–59 and Tp1214–224 epitopes dominate CD8 T-cell responses in BoLA-A10 and BoLA-18 MHC I homozygous animals, respectively. In this study, peptide–MHC I tetramers for these epitopes, and a subdominant BoLA-A10-restricted epitope (Tp298–106), were generated to facilitate accurate and rapid enumeration of epitope-specific CD8 T cells. During validation of these tetramers a substantial proportion of Tp249–59-reactive T cells failed to bind the tetramer, suggesting that this population was heterogeneous with respect to the recognized epitope. We demonstrate that Tp250–59 represents a distinct epitope and that tetramers produced with Tp50–59 and Tp49–59 show no cross-reactivity. The Tp249–59 and Tp250–59 epitopes use different serine residues as the N-terminal anchor for binding to the presenting MHC I molecule. Molecular dynamic modelling predicts that the two peptide–MHC I complexes adopt structurally different conformations and Tcell receptor β sequence analysis showed that Tp249–59 and Tp250–59 are recognized by non-overlapping T-cell receptor repertoires. Together these data demonstrate that although differing by only a single residue, Tp249–59 and Tp250–59 epitopes form distinct ligands for T-cell receptor recognition. Tetramer analysis of T. parva-specific CD8 T-cell lines confirmed the immunodominance of Tp1214–224 in BoLA-A18 animals and showed in BoLA-A10 animals that the Tp249–59 epitope response was generally more dominant than the Tp250–59 response and confirmed that the Tp298–106 response was subdominant

ASTRA: ASTrometry and phase-Referencing Astronomy on the Keck interferometer

ASTRA (ASTrometric and phase-Referencing Astronomy) is an upgrade to the existing Keck Interferometer which aims at providing new self-phase referencing (high spectral resolution observation of YSOs), dual-field phase referencing (sensitive AGN observations), and astrometric (known exoplanetary systems characterization and galactic center general relativity in strong field regime) capabilities. With the first high spectral resolution mode now offered to the community, this contribution focuses on the progress of the dual field and astrometric modes.Comment: 10 pages, 6 figures, 2 tables, SPIE 201

Early detection and intervention evaluation for people at risk of psychosis: multisite randomised controlled trial

Objective To determine whether cognitive therapy is effective in preventing the worsening of emerging psychotic symptoms experienced by help seeking young people deemed to be at risk for serious conditions such as schizophrenia

Permeating the social justice ideals of equality and equity within the context of Early Years: challenges for leadership in multi-cultural and mono-cultural primary schools

The ideology and commitment of social justice principles is central to Early Years practice, however, the term social justice in education is complex and remains contested. This paper explores the ideology of social justice through links between equality and equity and how it is embedded within Early Years, and what remain the potential challenges for leadership. Interviews in English multi-cultural and mono-cultural primary schools were conducted. Findings showed that the ideology of social justice, equality and equity was interpreted differently. Multi-cultural schools appear to use a greater variety of activities to embed social justice principles that involved their diverse communities more to enrich the curriculum. In mono-cultural schools leadership had to be more creative in promoting equality and equity given the smaller proportion of their diverse pupil and staff population. Tentative conclusions suggest that the vision for permeating equality and equity in Early Years, at best, is at early stages

A powerful intervention: general practitioners' use of sickness certification in depression

<b>Background</b> Depression is frequently cited as the reason for sickness absence, and it is estimated that sickness certificates are issued in one third of consultations for depression. Previous research has considered GP views of sickness certification but not specifically in relation to depression. This study aimed to explore GPs views of sickness certification in relation to depression.<p></p> <b>Methods</b> A purposive sample of GP practices across Scotland was selected to reflect variations in levels of incapacity claimants and antidepressant prescribing. Qualitative interviews were carried out between 2008 and 2009.<p></p> <b>Results</b> A total of 30 GPs were interviewed. A number of common themes emerged including the perceived importance of GP advocacy on behalf of their patients, the tensions between stakeholders involved in the sickness certification system, the need to respond flexibly to patients who present with depression and the therapeutic nature of time away from work as well as the benefits of work. GPs reported that most patients with depression returned to work after a short period of absence and that it was often difficult to predict which patients would struggle to return to work.<p></p> <b>Conclusions</b> GPs reported that dealing with sickness certification and depression presents distinct challenges. Sickness certificates are often viewed as powerful interventions, the effectiveness of time away from work for those with depression should be subject to robust enquiry

Core Schemas across the Continuum of Psychosis: A Comparison of Clinical and Non-Clinical Groups

This article has been accepted for publication and will appear in a revised form, subsequent to peer review and/or editorial input by Cambridge University Press, in Behavioural and Cognitive Psychotherapy published by Cambridge University Press. Copyright BABCP.Background: Research suggests that core schemas are important in both the development and maintenance of psychosis. Aims: The aim of the study was to investigate and compare core schemas in four groups along the continuum of psychosis and examine the relationships between schemas and positive psychotic symptomatology. Method: A measure of core schemas was distributed to 20 individuals experiencing first-episode psychosis (FEP), 113 individuals with “at risk mental states” (ARMS), 28 participants forming a help-seeking clinical group (HSC), and 30 non-help-seeking individuals who endorse some psychotic-like experiences (NH). Results: The clinical groups scored significantly higher than the NH group for negative beliefs about self and about others. No significant effects of group on positive beliefs about others were found. For positive beliefs about the self, the NH group scored significantly higher than the clinical groups. Furthermore, negative beliefs about self and others were related to positive psychotic symptomatology and to distress related to those experiences. Conclusions: Negative evaluations of the self and others appear to be characteristic of the appraisals of people seeking help for psychosis and psychosis-like experiences. The results support the literature that suggests that self-esteem should be a target for intervention. Future research would benefit from including comparison groups of people experiencing chronic psychosis and people who do not have any psychotic-like experiences

Anti-Inflammatory Effects of Metformin Irrespective of Diabetes Status

Rationale: The diabetes drug metformin is under investigation in cardiovascular disease but the molecular mechanisms underlying possible benefits are poorly understood. Objective: Here we have studied anti-inflammatory effects of the drug and their relationship to anti-hyperglycaemic properties. Methods and Results: In primary hepatocytes from healthy animals, metformin and the IKKβ inhibitor BI605906 both inhibited TNFα-dependent IκB degradation and expression of pro-inflammatory mediators IL-6, IL-1b, and CXCL1/2. Metformin suppressed IKKα/β activation, an effect which could be separated from some metabolic actions, in that BI605906 did not mimic effects of metformin on lipogenic gene expression, glucose production and AMPK activation. Equally AMPK was not required either for mitochondrial suppression of IκB degradation. Consistent with discrete anti-inflammatory actions, in macrophages metformin specifically blunted secretion of pro-inflammatory cytokines, without inhibiting M1/M2 differentiation or activation. In a large treatment naïve diabetes population cohort, we observed differences in the systemic inflammation marker, Neutrophil to Lymphocyte Ratio (NLR), following incident treatment with either metformin or sulfonylurea monotherapy. Compared to sulfonylurea exposure, metformin reduced the mean log-transformed NLR after 8-16 months by 0.09 units (95% CI=0.02-0.17, p=0.013), and increased the likelihood that NLR would be lower than baseline after 8-16 months (OR 1.83, 95% CI=1.22-2.75, p=0.00364). Following up these findings in a double blind placebo controlled trial in nondiabetic heart failure (trial registration: NCT00473876), metformin suppressed plasma cytokines including the ageing-associated cytokine CCL11. Conclusions: We conclude that anti-inflammatory properties of metformin are exerted irrespective of diabetes status. This may accelerate investigation of drug utility in non-diabetic cardiovascular disease groups