Mice expressing HLA-DQ6α8β transgenes develop polychondritis spontaneously

Relapsing polychondritis (RP) is a human autoimmune disease of unknown etiology in which cartilaginous sites are destroyed by cyclic inflammatory episodes beginning, most commonly, during the fourth or fifth decade of life. We have previously described collagen-induced polychondritis that closely mirrors RP occurring in young (6–8 weeks old) HLA-DQ6αβ8αβ transgenic Aβ0 mice, following immunization with heterologous type II collagen (CII). We present evidence here that transgenic strains expressing the DQ6α8β transgene develop spontaneous polychondritis (SP) at the mouse equivalent of human middle age (4.5–6 months and 40–50 years old, respectively) and display polyarthritis, auricular chondritis and nasal chondritis – three of the most common sites affected in RP. Auricular chondritis in SP, like RP but unlike CII-induced polychondritis, exhibited a relapsing/remitting phenotype, requiring several inflammatory cycles before the cartilage is destroyed. Elevated serum levels of total IgG corresponded with the onset of disease in SP, as in RP and CII-induced polychondritis. No CII-specific immune response was detected in SP, however – more closely mirroring RP, in which as few as 30% of RP patients have been reported to have CII-specific IgG. CII-induced polychondritis displays a strong CII-specific immune response. SP also demonstrated a strong female preponderance, as some workers have reported in RP but has not observed in CII-induced polychondritis. These characteristics of SP allow for the examination of the immunopathogenesis of polychondritis in the absence of an overwhelming CII-specific immune response and the strong adjuvant-induced immunostimulatory influence in CII-induced polychondritis. This spontaneous model of polychondritis provides a new and unique tool to investigate both the initiatory events as well as the immunopathogenic mechanisms occurring at cartilaginous sites during the cyclic inflammatory assaults of polychondritis

Reduced receptor editing in lupus-prone MRL/lpr mice

The initial B cell repertoire contains a considerable proportion of autoreactive specificities. The first major B cell tolerance checkpoint is at the stage of the immature B cell, where receptor editing is the primary mode of eliminating self-reactivity. The cells that emigrate from the bone marrow have a second tolerance checkpoint in the transitional compartment in the spleen. Although it is known that the second checkpoint is defective in lupus, it is not clear whether there is any breakdown in central B cell tolerance in the bone marrow. We demonstrate that receptor editing is less efficient in the lupus-prone strain MRL/lpr. In an in vitro system, when receptor-editing signals are given to bone marrow immature B cells by antiidiotype antibody or after in vivo exposure to membrane-bound self-antigen, MRL/lpr 3-83 transgenic immature B cells undergo less endogenous rearrangement and up-regulate recombination activating gene messenger RNA to a lesser extent than B10 transgenic cells. CD19, along with immunoglobulin M, is down-regulated in the bone marrow upon receptor editing, but the extent of down-regulation is fivefold less in MRL/lpr mice. Less efficient receptor editing could allow some autoreactive cells to escape from the bone marrow in lupus-prone mice, thus predisposing to autoimmunity

Feasibility of trial procedures for a randomised controlled trial of a community based group exercise intervention for falls prevention for visually impaired older people: the VIOLET study

Background Visually impaired older people (VIOP) have a higher risk of falling than their sighted peers, and are likely to avoid physical activity. The aim was to adapt the existing Falls Management Exercise (FaME) programme for VIOP, delivered in the community, and to investigate the feasibility of conducting a definitive randomised controlled trial (RCT) of this adapted intervention. Methods Two-centre randomised mixed methods pilot trial and economic evaluation of the adapted group-based FaME programme for VIOP versus usual care. A one hour exercise programme ran weekly over 12 weeks at the study sites (Newcastle and Glasgow), delivered by third sector (voluntary and community) organisations. Participants were advised to exercise at home for an additional two hours over the week. Those randomised to the usual activities group received no intervention. Outcome measures were completed at baseline, 12 and 24 weeks. The potential primary outcome was the Short Form Falls Efficacy Scale – International (SFES-I). Participants’ adherence was assessed by reviewing attendance records and self-reported compliance to the home exercises. Adherence with the course content (fidelity) by instructors was assessed by a researcher. Adverse events were collected in a weekly phone call. Results Eighteen participants, drawn from community-living VIOP were screened; 68 met the inclusion criteria; 64 participants were randomised with 33 allocated to the intervention and 31 to the usual activities arm. 94% of participants provided data at the 12 week visit and 92% at 24 weeks. Adherence was high. The intervention was found to be safe with 76% attending nine or more classes. Median time for home exercise was 50 min per week. There was little or no evidence that fear of falling, balance and falls risk, physical activity, emotional, attitudinal or quality of life outcomes differed between trial arms at follow-up. Conclusions The intervention, FaME, was implemented successfully for VIOP and all progression criteria for a main trial were met. The lack of difference between groups on fear of falling was unsurprising given it was a pilot study but there may have been other contributory factors including suboptimal exercise dose and apparent low risk of falls in participants. These issues need addressing for a future trial

Quality of life of adult retinoblastoma survivors in the Netherlands

This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

Diverse perspectives on interdisciplinarity from the Members of the College of the Royal Society of Canada

Various multiple-disciplinary terms and concepts (although most commonly “interdisciplinarity”, which is used herein) are used to frame education, scholarship, research, and interactions within and outside academia. In principle, the premise of interdisciplinarity may appear to have many strengths; yet, the extent to which interdisciplinarity is embraced by the current generation of academics, the benefits and risks for doing so, and the barriers and facilitators to achieving interdisciplinarity represent inherent challenges. Much has been written on the topic of interdisciplinarity, but to our knowledge there have been few attempts to consider and present diverse perspectives from scholars, artists, and scientists in a cohesive manner. As a team of 57 members from the Canadian College of New Scholars, Artists, and Scientists of the Royal Society of Canada (the College) who self-identify as being engaged or interested in interdisciplinarity, we provide diverse intellectual, cultural, and social perspectives. The goal of this paper is to share our collective wisdom on this topic with the broader community and to stimulate discourse and debate on the merits and challenges associated with interdisciplinarity. Perhaps the clearest message emerging from this exercise is that working across established boundaries of scholarly communities is rewarding, necessary, and is more likely to result in impact. However, there are barriers that limit the ease with which this can occur (e.g., lack of institutional structures and funding to facilitate cross-disciplinary exploration). Occasionally, there can be significant risk associated with doing interdisciplinary work (e.g., lack of adequate measurement or recognition of work by disciplinary peers). Solving many of the world’s complex and pressing problems (e.g., climate change, sustainable agriculture, the burden of chronic disease, and aging populations) demand thinking and working across long-standing, but in some ways restrictive, academic boundaries. Academic institutions and key support structures, especially funding bodies, will play an important role in helping to realize what is readily apparent to all who contributed to this paper—that interdisciplinarity is essential for solving complex problems; it is the new norm. Failure to empower and encourage those doing this research will serve as a great impediment to training, knowledge, and addressing societal issues

The Impact of Vision Impairment questionnaire: an examination of its domain structure using Confirmatory Factor Analysis and Rasch Analysis. Invest Ophthalmol Vis Sci

PURPOSE. To explore the psychometric properties of the Impact of Vision Impairment scale (IVI) by using Rasch analysis. METHODS. Three hundred fourteen first-time referrals to lowvision clinics completed the 32-item IVI. The data were Raschanalyzed with a partial credit model using RUMM2020 software (RUMM Laboratory, Perth, WA, Australia). The overall fit of the model, response scale, individual item fit, differential item functioning, unidimensionality, and person-separation reliability were assessed. RESULTS. Initially, 26 items displayed disordered thresholds. However, collapsing the response scale to three categories (4 items) and four categories (28 items) produced ordered response thresholds for all items. Four items with high proportions of missing responses, poor spread, high skewness, and deviation between observed and expected model curves were then removed. This adjustment produced overall fit to the Rasch model (item-trait interaction 2 ϭ 118.3; P ϭ 0.32). The final mean (SD) person and item fit residuals ere 0.06 (0.85) and Ϫ0.20 (1.45), respectively. The person-separation reliability was 0.9, indicating that the scale was able to discriminate between several different groups of participants. The revised scale was well targeted to the participants, with similar mean locations for items (0.00) and persons (0.16). A significant difference between participants of mild, moderate, and severe visual impairment (ANOVA; P 0.001) supported the criterion validity of the Rasch-scaled IVI. CONCLUSIONS. The results provide support for the measurement properties of the Rasch-scaled 28-item version of the IVI and of its potential for assessing outcomes of low-vision rehabilitation. A raw score-to-Rasch person measure conversion is supplied. (Invest Ophthalmol Vis Sci. 2006;47:4732-4741

The impact of vision impairment questionnaire: an evaluation of its measurement properties using Rasch analysis

PURPOSE. To explore the psychometric properties of the Impact of Vision Impairment scale (IVI) by using Rasch analysis. METHODS. Three hundred fourteen first-time referrals to low-vision clinics completed the 32-item IVI. The data were Rasch-analyzed with a partial credit model using RUMM2020 software (RUMM Laboratory, Perth, WA, Australia). The overall fit of the model, response scale, individual item fit, differential item functioning, unidimensionality, and person-separation reliability were assessed. RESULTS. Initially, 26 items displayed disordered thresholds. However, collapsing the response scale to three categories (4 items) and four categories (28 items) produced ordered response thresholds for all items. Four items with high proportions of missing responses, poor spread, high skewness, and deviation between observed and expected model curves were then removed. This adjustment produced overall fit to the Rasch model (item-trait interaction X2 = 118.3; P = 0.32). The final mean (SD) person and item fit residuals ere 0.06 (0.85) and -0.20 (1.45), respectively. The person-separation reliability was 0.9, indicating that the scale was able to discriminate between several different groups of participants. The revised scale was well targeted to the participants, with similar mean locations for items (0.00) and persons (0.16). A significant difference between participants of mild, moderate, and severe visual impairment (ANOVA; P 0.001) supported the criterion validity of the Rasch-scaled IVI. CONCLUSIONS. The results provide support for the measurement properties of the Rasch-scaled 28-item version of the IVI and of its potential for assessing outcomes of low-vision rehabilitation. A raw score-to-Rasch person measure conversion is supplied

The effectiveness of low-vision rehabilitation on participation in daily living and quality of life

Purpose: To evaluate the effectiveness of a multidisciplinary low-vision rehabilitation program on quality of life evaluated by the Impact of Vision Impairment (IVI) instrument. Methods: First-time referrals to low-vision clinics were assessed before and after rehabilitation (3–6 months). Rasch analysis was used to estimate the three IVI subscale and overall values on an interval scale. A mixed between–within subjects ANOVA was used to identify whether presenting visual acuity had an interaction effect with rehabilitation change. Cohen d values were used to estimate the magnitude of the change and the standardized response mean (SRM) procedure was selected to determine the clinical significance of the rehabilitation-induced changes. Results: One hundred twenty-four women and 68 men (mean age, 80.3 years) completed the rehabilitation. Most had age-related macular degeneration (62%, 119) and were moderately to severely vision impaired (<6/18; 78%, 149). After rehabilitation, significant improvements were recorded for the overall IVI score (P = 0.006) and two subscales: reading and accessing information and emotional well-being (P = 0.007 and 0.009, respectively). No significant improvement was found on the mobility and independence subscale (P = 0.07). The magnitude of the postintervention improvement was found to be relatively moderate (Cohen d = 0.17–0.30) and clinically modest (SRM = 0.22–0.42). Conclusions: Significant improvements in overall quality of life and two specific areas of daily living in people with low vision were found, although the magnitude and clinical significance of the rehabilitation-induced gains were modest. Further investigation in other models of low-vision rehabilitation is needed to optimize quality of life gains in people with low vision

The impact of vision impairment questionnaire: an assessment of its domain structure using confirmatory factor analysis and rasch analysis

Purpose: To assess and validate the subscale structure of the 28-item Impact of Visual Impairment (IVI) Scale by using confirmatory factor analysis (CFA) and Rasch analysis for use as an outcome measure. Methods: Three hundred nineteen participants completed the IVI questionnaire, and the responses then were subjected to Rasch analysis by RUMM2020 software. With the person estimates for each item, CFA was used to assess two hypothesized structures: three-and four-factor models. The subscales of the model with the best fit were then further validated by Rasch analysis. Results: CFA supported a three-factor model that included items from the emotional well-being, reading and accessing information, and mobility and independence subscales. Almost all the selected goodness-of-fit statistics for the three-factor model were better than the recommended values. The factor loadings of the items on their respective domains were all statistically significant (P < 0.001) and ranged between 0.54 and 0.81. The three subscales individually fitted the Rasch model according to the item–trait interaction test (mobility and independence {chi}2 [df] = 45.9 [44], P = 0.39; emotional well-being = 28.4 [32], P = 0.65; and reading and accessing information = 43.5 [36], P = 0.18). The item-fit residuals values of the three subscales were <2.5 and showed mean and standard deviations approximating 0 and 1, respectively. The internal consistency reliability of the subscales ({alpha}) was substantial, ranging between 0.89 and 0.91. Conclusions: An examination of the IVI dimension confirmed a three-subscale structure that displays interval measurement characteristics likely to provide a valid and reliable assessment of restriction of participation. The findings provide an opportunity for a more detailed measurement of the effects of different types of low-vision rehabilitation programs