Change in CD3 positive T-cell expression in psoriatic arthritis synovium correlates with change in DAS28 and magnetic resonance imaging synovitis scores following initiation of biologic therapy - a single centre, open-label study

With the development of increasing numbers of potential therapeutic agents in inflammatory disease comes the need for effective biomarkers to help screen for drug efficacy and optimal dosing regimens early in the clinical trial process. This need has been recognized by the Outcome Measures in Rheumatology Clinical Trials (OMERACT) group, which has established guidelines for biomarker validation. To seek a candidate synovial biomarker of treatment response in psoriatic arthritis (PsA), we determined whether changes in immunohistochemical markers of synovial inflammation correlate with changes in disease activity scores assessing 28 joints (ΔDAS28) or magnetic resonance imaging synovitis scores (ΔMRI) in patients with PsA treated with a biologic agent. Twenty-five consecutive patients with PsA underwent arthroscopic synovial biopsies and MRI scans of an inflamed knee joint at baseline and 12 weeks after starting treatment with either anakinra (first 10 patients) or etanercept (subsequent 15 patients) in two sequential studies of identical design. DAS28 scores were measured at both time points. Immunohistochemical staining for CD3, CD68 and Factor VIII (FVIII) was performed on synovial samples and scored by digital image analysis (DIA). MRI scans performed at baseline and at 12 weeks were scored for synovitis semi-quantitatively. The ΔDAS28 of the European League Against Rheumatism good response definition (>1.2) was chosen to divide patients into responder and non-responder groups. Differences between groups (Mann Whitney U test) and correlations between ΔDAS28 with change in immunohistochemical and MRI synovitis scores (Spearman's rho test) were calculated. Paired synovial samples and MRI scans were available for 21 patients (8 anakinra, 13 etanercept) and 23 patients (8 anakinra, 15 etanercept) respectively. Change in CD3 (ΔCD3) and CD68 expression in the synovial sublining layer (ΔCD68sl) was significantly greater in the disease responders compared to non-responders following treatment (P = 0.005 and 0.013 respectively). ΔCD3, but not ΔCD68 or ΔFVIII, correlated with both ΔDAS28 (r = 0.49, P = 0.025) and ΔMRI (r = 0.58, P = 0.009). The correlation of ΔCD3 with ΔDAS28 and ΔMRI following biologic treatment in this cohort contributes to the validation of ΔCD3 as a synovial biomarker of disease response in PsA, and supports the further evaluation of ΔCD3 for predictive properties of future clinical outcome

Alcoholism and recovery: A case study of a former professional footballer

What little we know about alcoholism amongst professional footballers comes largely from the media (often tabloid newspapers) and published autobiographies and biographies of high profile stars. The coverage often focuses on deviant behaviour when drunk, such as driving under the influence, marital infidelity, violence, and breaking team rules. There is little or no published research which seeks to understand better what it is like to suffer from alcoholism from the perspective of the player-addicts themselves. In this paper I present a case study of British footballer who had a brief professional career and is in recovery from alcoholism. His subjective experience of alcoholism provides valuable insights into the underlying triggers and/or causes of the illness; its destructive nature; the link between the individual’s addiction and his social circumstances (including football); and his recovery

Polymer Flow Through Porous Media: Numerical Prediction of the Contribution of Slip to the Apparent Viscosity.

The flow of polymer solutions in porous media is often described using Darcy’s law with an apparent viscosity capturing the observed thinning or thickening effects. While the macroscale form is well accepted, the fundamentals of the pore-scale mechanisms, their link with the apparent viscosity, and their relative influence are still a matter of debate. Besides the complex effects associated with the rheology of the bulk fluid, the flow is also deeply influenced by the mechanisms occurring close to the solid/liquid interface, where polymer molecules can arrange and interact in a complex manner. In this paper, we focus on a repulsive mechanism, where polymer molecules are pushed away from the interface, yielding a so-called depletion layer in the vicinity of the wall. This depletion layer acts as a lubricating film that may be represented by an effective slip boundary condition. Here, our goal is to provide a simple mean to evaluate the contribution of this slip effect to the apparent viscosity. To do so, we solve the pore-scale flow numerically in idealized porous media with a slip length evaluated analytically in a tube. Besides its simplicity, the advantage of our approach is also that it captures relatively well the apparent viscosity obtained from core-flood experiments, using only a limited number of inputs. Therefore, it may be useful in many applications to rapidly estimate the influence of the depletion layer effect over the macroscale flow and its relative contribution compared to other phenomena, such as non-Newtonian effects

Celtic pilgrimage, past and present: from historical geography to contemporary embodied practices

Perigrinatio, the Latin term for pilgrimage was at the heart of the medieval Celtic church, but was this was understood and practised not only as a journey to a shrine, but more broadly as a spiritual journey, which could lead to an isolated hermitage or peripatetic evangelistic mission. In this paper, we outline the beliefs and practices of the broad assemblage known as the Celtic church, particularly the interleaving of pilgrimage, asceticism and landscape poetics, and how these have informed continued and renewed pilgrimage practices to sites of the early Celtic church by particular denominations, ecumenical groups and those interested in broader spiritualities. These sacred mobilities are explored through vignettes of embodied-emotionalspiritual practices situated in the landscapes and faith communities of Lough Derg,Ireland and the Isle of Man. They share geographical marginality, a focus on multiple Celtic saints and an enduring belief in the immanence of God, expressed through embodied spiritual practice in the landscape. However, they differ widely in matters of institutionalised structure, regulation, discursive scripting and gendered hierarchy, reflecting situated and denominational preferences for the ascetic and aesthetic spiritual legacies of the medieval Celtic church

A comparison of three Peyer's patch "M-like" cell culture models: particle uptake, bacterial interaction, and epithelial histology

Intestinal Peyer's patch (PP) microfold (M) cells transport microbes and particulates across the follicle-associated epithelium (FAE) as part of the mucosal immune surveillance system. In vitro human M-like cell co-culture models are used as screens to investigate uptake of antigens-in-nanoparticles, but the models are labour-intensive and there is inter-laboratory variability. We compared the three most established filter-grown Caco-2/Raji B cell co-culture systems. These were Model A (Kerneis et al, 1997), Model B (Gullberg et al., 2000), and Model C (Des Rieux et al. 2007). The criteria used were transepithelial resistance (TEER), the apparent permeability coefficient (Papp) of [(14)C]-mannitol, M cell-like histology, as well as latex particle and Salmonella typhimurium translocation. Each co-culture model displayed substantial increases in particle translocation. Truncated microvilli compared to mono-cultures was their most consistent feature. The inverted model developed by des Rieux et al. (2007) displayed reductions in TEER and an increased (Papp), accompanied by the largest increase in particle translocation compared to the other two models. The normally-oriented model developed by Gullberg et al. (2000) was the only one to consistently display an increased translocation of salmonella typhimurium. By applying a double Matrigel¿¿¿ coating on filters, altering the medium feeding regime for Raji B cells, and restricting the passage number of B cells, improvements to the Gullberg model B were achieved, as reflected by increased particle translocation and improved histology. In conclusion, this is the first time all three designs have been compared in one study and each displays phenotypic features of M-like cells. While Model C was the most robust co-culture, the Model B protocol could be improved by optimizing several variables and is less complicated to establish than the two inverted models..Science Foundation Irelan