Participatory development and analysis of a fuzzy cognitive map of the establishment of a bio-based economy in the Humber region.

Fuzzy Cognitive Mapping (FCM) is a widely used participatory modelling methodology in which stakeholders collaboratively develop a 'cognitive map' (a weighted, directed graph), representing the perceived causal structure of their system. This can be directly transformed by a workshop facilitator into simple mathematical models to be interrogated by participants by the end of the session. Such simple models provide thinking tools which can be used for discussion and exploration of complex issues, as well as sense checking the implications of suggested causal links. They increase stakeholder motivation and understanding of whole systems approaches, but cannot be separated from an intersubjective participatory context. Standard FCM methodologies make simplifying assumptions, which may strongly influence results, presenting particular challenges and opportunities. We report on a participatory process, involving local companies and organisations, focussing on the development of a bio-based economy in the Humber region. The initial cognitive map generated consisted of factors considered key for the development of the regional bio-based economy and their directional, weighted, causal interconnections. A verification and scenario generation procedure, to check the structure of the map and suggest modifications, was carried out with a second session. Participants agreed on updates to the original map and described two alternate potential causal structures. In a novel analysis all map structures were tested using two standard methodologies usually used independently: linear and sigmoidal FCMs, demonstrating some significantly different results alongside some broad similarities. We suggest a development of FCM methodology involving a sensitivity analysis with different mappings and discuss the use of this technique in the context of our case study. Using the results and analysis of our process, we discuss the limitations and benefits of the FCM methodology in this case and in general. We conclude by proposing an extended FCM methodology, including multiple functional mappings within one participant-constructed graph.

Employment of a needs assessment survey to shape a novel web-based pediatric rheumatology curriculum for primary care providers.

BACKGROUND: Pediatric rheumatology faces many challenges due to the shortage of board certified physicians in the field and the imbalance in their geographic distribution. This shortage has required primary care physicians and adult rheumatologists to assume the care of children with rheumatologic diseases, though these physicians report significant discomfort doing so. We are addressing this issue through the development of a novel web-based curriculum aimed at primary care physicians. METHODS: We pursued a needs assessment survey of Vanderbilt pediatric residency graduates (1981-2010) working in primary care. Our goals were to understand their perceptions of what the needs are and what educational interventions would be most effective. RESULTS: Of 152 surveys sent successfully via Survey Monkey, we received 28 responses (18.4%). Responses suggest there to be a discrepancy between physicians' general assessment of their training and their self-reported ability to recognize specific diseases. Nearly 80% of respondents felt that additional education in pediatric rheumatology would improve their ability to co-manage children with the rheumatologist. Action plans for common rheumatologic complaints and potential emergencies were thought to be of potential benefit by a majority of respondents. CONCLUSIONS: We will utilize our survey results to develop a learner centered curriculum to have the highest positive impact in assisting primary care providers in caring for children with rheumatologic diseases.

Algorithm development for corticosteroid management in systemic juvenile idiopathic arthritis trial using consensus methodology.

BACKGROUND: The management of background corticosteroid therapy in rheumatology clinical trials poses a major challenge. We describe the consensus methodology used to design an algorithm to standardize changes in corticosteroid dosing during the Randomized Placebo Phase Study of Rilonacept in Systemic Juvenile Idiopathic Arthritis Trial (RAPPORT). METHODS: The 20 RAPPORT site principal investigators (PIs) and 4 topic specialists constituted an expert panel that participated in the consensus process. The panel used a modified Delphi Method consisting of an on-line questionnaire, followed by a one day face-to-face consensus conference. Consensus was defined as ≥ 75% agreement. For items deemed essential but when consensus on critical values was not achieved, simple majority vote drove the final decision. RESULTS: The panel identified criteria for initiating or increasing corticosteroids. These included the presence or development of anemia, myocarditis, pericarditis, pleuritis, peritonitis, and either complete or incomplete macrophage activation syndrome (MAS). The panel also identified criteria for tapering corticosteroids which included absence of fever for ≥ 3 days in the previous week, absence of poor physical functioning, and seven laboratory criteria. A tapering schedule was also defined. CONCLUSION: The expert panel established consensus regarding corticosteroid management and an algorithm for steroid dosing that was well accepted and used by RAPPORT investigators. Developed specifically for the RAPPORT trial, further study of the algorithm is needed before recommendation for more general clinical use.

Classification, presentation, and initial treatment of Wegener's granulomatosis in childhood.

OBJECTIVE: To compare the criteria for Wegener's granulomatosis (WG) of the American College of Rheumatology (ACR) with those of the European League Against Rheumatism/Pediatric Rheumatology European Society (EULAR/PRES) in a cohort of children with WG and other antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAVs), and to describe the interval to diagnosis, presenting features, and initial treatment for WG. METHODS: Eligible patients had been diagnosed by site rheumatologists (termed the "MD diagnosis") since 2004. This diagnosis was used as a reference standard for sensitivity and specificity testing of the 2 WG classification criteria. Descriptive analyses were confined to ACR-classified WG patients. RESULTS: MD diagnoses of 117 patients (82 of whom were female) were WG (n = 76), microscopic polyangiitis (n = 17), ANCA-positive pauci-immune glomerulonephritis (n = 5), Churg-Strauss syndrome (n = 2), and unclassified vasculitis (n = 17). The sensitivities of the ACR and EULAR/PRES classification criteria for WG among the spectrum of AAVs were 68.4% and 73.6%, respectively, and the specificities were 68.3% and 73.2%, respectively. Two more children were identified as having WG by the EULAR/PRES criteria than by the ACR criteria. For the 65 ACR-classified WG patients, the median age at diagnosis was 14.2 years (range 4-17 years), and the median interval from symptom onset to diagnosis was 2.7 months (range 0-49 months). The most frequent presenting features by organ system were constitutional (89.2%), pulmonary (80.0%), ear, nose, and throat (80.0%), and renal (75.4%). Fifty-four patients (83.1%) commenced treatment with the combination of corticosteroids and cyclophosphamide, with widely varying regimens; the remainder received methotrexate alone (n = 1), corticosteroids alone (n = 4), or a combination (n = 6). CONCLUSION: The EULAR/PRES criteria minimally improved diagnostic sensitivity and specificity for WG among a narrow spectrum of children with AAVs. Diagnostic delays may result from poor characterization of childhood WG. Initial therapy varied considerably among participating centers.

Mutations of the hemophagocytic lymphohistiocytosis-associated gene UNC13D in a patient with systemic juvenile idiopathic arthritis.

The clinical syndromes of hemophagocytic lymphohistiocytosis (HLH) and macrophage activation syndrome (MAS) are both characterized by dysregulated inflammation with prolonged fever, hepatosplenomegaly, coagulopathy, hematologic cytopenias, and evidence of hemophagocytosis in the bone marrow or liver. While HLH is either inherited or acquired, children with severe rheumatic diseases, most notably systemic juvenile idiopathic arthritis, are at risk for MAS. The phenotypic similarity between HLH and MAS raises the possibility that they share common pathogenetic mechanisms. Familial forms of HLH have been attributed to mutations in the genes encoding perforin (PRF1) and Munc13-4 (UNC13D), among others, and are characterized by defective cytotoxic lymphocyte function. While some patients with systemic JIA have decreased levels of perforin protein expression and natural killer (NK) cell function, mutations of HLH-associated genes in patients with systemic JIA have not been reported. We report the case of an 8-year-old girl with systemic JIA without MAS who was found to have compound heterozygous mutations of UNC13D and reduced NK cell cytotoxic function. This case broadens the range of clinical phenotypes attributable to UNC13D mutations and offers new insights into the etiology and pathogenesis of systemic JIA.

Celiac disease presenting with chilblains in an adolescent girl.

Chilblains, or pernio, are cutaneous lesions that may accompany systemic illnesses including states of malnutrition and autoimmune diseases. We report an adolescent girl in whom chilblains were the chief presenting sign of celiac disease. A gluten-free diet led to weight gain and resolution of the chilblains. We speculate that in this patient, weight loss due to celiac disease contributed to the development of chilblains.

Mast cells regulate IFN-gamma expression in the skin and circulating IgE levels in allergen-induced skin inflammation.

BACKGROUND: Mast cells are important effector cells in IgE-mediated allergic reactions. They are present in normal skin and increased in skin lesions of patients with atopic dermatitis (AD). OBJECTIVE: We used mice deficient in mast cells (W/W(v)) to assess the role of these cells in a murine model of allergen-induced skin inflammation induced by repeated epicutaneous sensitization with ovalbumin (OVA); the model exhibits many of the characteristics of AD. METHODS: Mice deficient in mast cells were sensitized with OVA. Histologic and immunohistochemical examinations, as well as measurements of IL-4 and IFN-gamma mRNA, were performed on OVA-sensitized skin. Total and antigen-specific serum IgE levels were determined. RESULTS: Infiltration in W/W(v) mice by mononuclear cells, T cells, and eosinophils in OVA-sensitized skin was comparable to that in wild-type (WT) controls. Expression of IL-4 mRNA in sensitized skin sites was similarly increased in WT and W/W(v) mice. However, IFN-gamma mRNA expression was significantly increased in sensitized skin of W/W(v) mice but not in that of WT controls. IL-4 mRNA was readily detectable in unsensitized skin of WT controls but not in that of W/W,(v) mice, whereas expression of IL-12 p40 mRNA was significantly increased in unsensitized skin of W/W(v) mice in comparison with WT controls. Total serum IgE levels were significantly increased after epicutaneous sensitization in W/W(v) mice in comparison with WT controls. CONCLUSION: These results suggest that mast cells regulate IFN-gamma expression in the skin and IgE levels in the circulation in a model of allergen-induced skin inflammation with similarities to AD. This is important, given the role of IFN-gamma in keratinocyte injury in AD and the role of IgE-mediated reactions in exacerbating AD.