Interactive drama in real and virtual worlds.

How do we resolve the paradox of computer-supported interactive drama - that the human participant requires the very freedom to interact that the authored narrative structure denies them? This paper reports work around the concept of Emergent Narrative - the development of narrative structure through interaction itself. We cover both systems using a virtual world and those using a virtually-augmented real world, exploring how far reworking narrative structure as a loop between the causal (plot) and affective (character) can produce engaging experiences for participants. We discuss the key role of a cognitive-affective architecture for charac-ters and the process of cognitive appraisal as an engine for both in-character and in-role dramatic action

Innate Immunity in Rheumatoid and Psoriatic Arthritis. Toll-like Receptors as Mediators of Disease

Contains fulltext : 93619.pdf (publisher's version ) (Open Access)Radboud Universiteit Nijmegen, 15 juni 2012Promotor : Riel, P.L.C.M. van Co-promotor : Radstake, T.R.D.J.253 p

Antigen-presenting cells and their Fcy and Toll-like receptors: Leading suspects in autoimmunity.

Contains fulltext : 88238.pdf (publisher's version ) (Open Access

Fc gamma receptor mediated modulation of dendritic cells as a potential strategy in the battle against rheumatoid arthritis.

Contains fulltext : 49335.pdf (publisher's version ) (Open Access)Autoimmune diseases such as rheumatoid arthritis (RA) result from a deregulation of immune responses culminating in immune-mediated tissue injury. In RA, this tissue injury is mainly reflected by synovitis and subsequent joint damage, although involvement of visceral organs (heart, lungs and kidneys) often leads to severe comorbidity. Accumulating evidence points towards dendritic cells (DC) as the principal regulators of the balance between immunity and tolerance. Recently, a large body of evidence has demonstrated that the balance between activating and inhibitory Fc gamma receptor (Fc gammaR) subtypes is intricately involved in the regulation of DC behaviour. In this overview we summarise recent findings from our group and others that suggest an important role for Fc gammaR in arthritis. Furthermore, we postulate novel mechanisms of how triggering of Fc gammaR might be used to manipulate DC function and combat autoimmunity. When DC are envisaged as useful targets in the light of DC immunotherapy in RA, detailed knowledge on the regulatory pathways of Fc gammaR in RA is of paramount importance

Dendritic cells and their potential implication in pathology and treatment of rheumatoid arthritis.

Item does not contain fulltextDendritic cells (DC) are the professional antigen presenting cells that protect us against invading organisms. On the other hand, they uphold tolerance thereby avoiding the initiation of autoimmunity. In performing these contrasting but essential tasks DC are unique and divide these processes in time and space. It is often thought that a loss of separation of these tasks underlies the breakthrough of tolerance leading to autoimmune conditions such as rheumatoid arthritis. In this review, we will focus on the evidence which points towards the implication of DC in the inflammatory process observed in RA and in experimental models of arthritis. Finally, we will conclude on future programs exploiting the capacity of DC to cure conditions such as RA

Measuring disease activity in psoriatic arthritis: PASDAS implementation in a tightly monitored cohort reveals residual disease burden

Item does not contain fulltex

Implementing Psoriatic Arthritis Disease Activity Score-guided treat-to-target in psoriatic arthritis routine clinical practice: (im)possible?

Item does not contain fulltex

Abatacept modulates proinflammatory macrophage responses upon cytokine-activated T cell and Toll-like receptor ligand stimulation

<p>Objectives: We investigated whether Abatacept might reduce proinflammatory cytokine production by macrophages upon contact with cytokine activated T cells and/or stimulation with TLR ligands.</p> <p>Methods: Macrophages and cytokine stimulated T cells (Tck) were added together in the presence of Abatacept or a control Ig, with or without TLR ligands. The production of cytokines was determined by luminex.</p> <p>Results: Abatacept reduced Tck-induced production of TNFa by macrophages. Tck and TLR ligands synergistically induced the production of proinflammatory cytokines by macrophages, especially IL-12p70. The production of IL-12p70 coincided with the production of IFNg, which were both reduced in the presence of Abatacept.</p> <p>Conclusions: Tck induce the production of TNFa by macrophages and facilitate the highly increased production of proinflammatory cytokines in the presence of TLR ligands. Abatacept was shown to potently suppress these pathways suggesting that its role may extend beyond antigen specific T cell mediated effector function.</p&gt

Discovery of Psoriatic Arthritis in Psoriasis Patients for Early Rheumatological Referral (DAPPER) Study: A Prospective Observational Cohort

Patients with psoriasis are at risk of developing psoriatic arthritis, which can lead to irreversible joint damage. However, a proportion of patients with psoriasis and concomitant psoriatic arthritis remain undiscovered in practice. The aims of this study were: to prospectively determine prevalence, characteristics, and disease burden of psoriatic arthritis in a psoriasis population; and to determine the prevalence and characteristics of patients with active psoriatic arthritis, who were not under rheumatological care. Patients with psoriasis were screened by a rheumatologist at the dermatology outpatient clinic for psoriatic arthritis. Patients with suspected active psoriatic arthritis who were not seeing a rheumatologist were referred to a rheumatologist for confirmation. The total prevalence of psoriatic arthritis in this observational, prospective cohort (n = 303) was 24%. Patients with psoriasis with concomitant psoriatic arthritis had longer duration of skin disease and more often a treatment history with systemic therapies. In this academic, specialized, setting, 2.3% of patients (n = 7), were not receiving rheumatological care despite having active psoriatic arthritis. These patients were characterized by a combination of low (perceived) disease burden and low yield of screening questionnaires, making it difficult for dermatologists to discover psoriatic arthritis in these patients. Thus, screening for more subtle active arthritis in patients with psoriasis in a dermatology setting could be improved

The functional variant (Asp299gly) of toll-like receptor 4 (TLR4) influences TLR4-mediated cytokine production in rheumatoid arthritis.

OBJECTIVE: To investigate functional consequences of the Toll-like receptor 4 (TLR4) variant (Asp299Gly) in rheumatoid arthritis (RA). METHODS: Peripheral blood mononuclear cells from 28 patients with RA carrying or not carrying the TLR4 variant were incubated with lipopolysaccharide (LPS) and heat shock protein B8 (HSPB8). Concentrations of interleukin 6 (IL-6), tumor necrosis factor-alpha(TNF-alpha), and IL-10 were determined along with TLR4 and CD14 expression. RESULTS: TLR4 expression was similar in patients carrying or not carrying the variant. In contrast, both LPS and HSPB8 resulted in significantly lower secretion of IL-6, TNF-alpha, and IL-10 in those who carried the variant, whereas the frequency of CD14+ cells was higher in these individuals. CONCLUSION: TLR4 variant clearly reduces its potency to mediate signaling. Correction for CD14+ cells is necessary in comparable experiments