Protocol for the Foot in Juvenile Idiopathic Arthritis trial (FiJIA): a randomised controlled trial of an integrated foot care programme for foot problems in JIA

<b>Background</b>: Foot and ankle problems are a common but relatively neglected manifestation of juvenile idiopathic arthritis. Studies of medical and non-medical interventions have shown that clinical outcome measures can be improved. However existing data has been drawn from small non-randomised clinical studies of single interventions that appear to under-represent the adult population suffering from juvenile idiopathic arthritis. To date, no evidence of combined therapies or integrated care for juvenile idiopathic arthritis patients with foot and ankle problems exists. <b>Methods/design</b>: An exploratory phase II non-pharmacological randomised controlled trial where patients including young children, adolescents and adults with juvenile idiopathic arthritis and associated foot/ankle problems will be randomised to receive integrated podiatric care via a new foot care programme, or to receive standard podiatry care. Sixty patients (30 in each arm) including children, adolescents and adults diagnosed with juvenile idiopathic arthritis who satisfy the inclusion and exclusion criteria will be recruited from 2 outpatient centres of paediatric and adult rheumatology respectively. Participants will be randomised by process of minimisation using the Minim software package. The primary outcome measure is the foot related impairment measured by the Juvenile Arthritis Disability Index questionnaire's impairment domain at 6 and 12 months, with secondary outcomes including disease activity score, foot deformity score, active/limited foot joint counts, spatio-temporal and plantar-pressure gait parameters, health related quality of life and semi-quantitative ultrasonography score for inflammatory foot lesions. The new foot care programme will comprise rapid assessment and investigation, targeted treatment, with detailed outcome assessment and follow-up at minimum intervals of 3 months. Data will be collected at baseline, 6 months and 12 months from baseline. Intention to treat data analysis will be conducted. A full health economic evaluation will be conducted alongside the trial and will evaluate the cost effectiveness of the intervention. This will consider the cost per improvement in Juvenile Arthritis Disability Index, and cost per quality adjusted life year gained. In addition, a discrete choice experiment will elicit willingness to pay values and a cost benefit analysis will also be undertaken

The Immunomodulatory Role of Adjuvants in Vaccines Formulated with the Recombinant Antigens Ov-103 and Ov-RAL-2 against Onchocerca volvulus in Mice.

BACKGROUND: In some regions in Africa, elimination of onchocerciasis may be possible with mass drug administration, although there is concern based on several factors that onchocerciasis cannot be eliminated solely through this approach. A vaccine against Onchocerca volvulus would provide a critical tool for the ultimate elimination of this infection. Previous studies have demonstrated that immunization of mice with Ov-103 and Ov-RAL-2, when formulated with alum, induced protective immunity. It was hypothesized that the levels of protective immunity induced with the two recombinant antigens formulated with alum would be improved by formulation with other adjuvants known to enhance different types of antigen-specific immune responses. METHODOLOGY/ PRINCIPAL FINDINGS: Immunizing mice with Ov-103 and Ov-RAL-2 in conjunction with alum, Advax 2 and MF59 induced significant levels of larval killing and host protection. The immune response was biased towards Th2 with all three of the adjuvants, with IgG1 the dominant antibody. Improved larval killing and host protection was observed in mice immunized with co-administered Ov-103 and Ov-RAL-2 in conjunction with each of the three adjuvants as compared to single immunizations. Antigen-specific antibody titers were significantly increased in mice immunized concurrently with the two antigens. Based on chemokine levels, it appears that neutrophils and eosinophils participate in the protective immune response induced by Ov-103, and macrophages and neutrophils participate in immunity induced by Ov-RAL-2. CONCLUSIONS/SIGNIFICANCE: The mechanism of protective immunity induced by Ov-103 and Ov-RAL-2, with the adjuvants alum, Advax 2 and MF59, appears to be multifactorial with roles for cytokines, chemokines, antibody and specific effector cells. The vaccines developed in this study have the potential of reducing the morbidity associated with onchocerciasis in humans

Mapping genetic variations to three- dimensional protein structures to enhance variant interpretation: a proposed framework

The translation of personal genomics to precision medicine depends on the accurate interpretation of the multitude of genetic variants observed for each individual. However, even when genetic variants are predicted to modify a protein, their functional implications may be unclear. Many diseases are caused by genetic variants affecting important protein features, such as enzyme active sites or interaction interfaces. The scientific community has catalogued millions of genetic variants in genomic databases and thousands of protein structures in the Protein Data Bank. Mapping mutations onto three-dimensional (3D) structures enables atomic-level analyses of protein positions that may be important for the stability or formation of interactions; these may explain the effect of mutations and in some cases even open a path for targeted drug development. To accelerate progress in the integration of these data types, we held a two-day Gene Variation to 3D (GVto3D) workshop to report on the latest advances and to discuss unmet needs. The overarching goal of the workshop was to address the question: what can be done together as a community to advance the integration of genetic variants and 3D protein structures that could not be done by a single investigator or laboratory? Here we describe the workshop outcomes, review the state of the field, and propose the development of a framework with which to promote progress in this arena. The framework will include a set of standard formats, common ontologies, a common application programming interface to enable interoperation of the resources, and a Tool Registry to make it easy to find and apply the tools to specific analysis problems. Interoperability will enable integration of diverse data sources and tools and collaborative development of variant effect prediction methods

An Online Evidence-Based Decision Support System for Distinguishing Benign from Malignant Vertebral Compression Fractures by Magnetic Resonance Imaging Feature Analysis

Decision support systems have been used to promote the practice of evidence-based medicine. Computer-assisted diagnosis can serve as one element of evidence-based radiology. One area where such tools may provide benefit is analysis of vertebral compression fractures (VCFs), which can be a challenge in MRI interpretation. VCFs may be benign or malignant in etiology, and several MRI features may help to make this important distinction. We describe a web-based decision support system for discriminating benign from malignant VCFs as a prototype for a more general diagnostic decision support framework for radiologists. The system has three components: a feature checklist with an image gallery derived from proven reference cases, a prediction model, and a reporting mechanism. The website allows users to input the findings for a case to be interpreted using a structured feature checklist. The image gallery complements the checklist, for clarity and training purposes. The input from the checklist is then used to calculate the likelihood of malignancy by a logistic regression prediction model. Standardized report text is generated that summarizes pertinent positive and negative findings. This computer-assisted diagnosis system demonstrates the integration of three areas where diagnostic decision support can aid radiologists: first, in image interpretation, through feature checklists and illustrative image galleries; second, in feature-based prediction modeling; and third, in structured reporting. We present a diagnostic decision support tool that provides radiologists with evidence-based guidance for discriminating benign from malignant VCF. This model may be useful in other difficult-diagnosis situations and requires further clinical testing

Does the Dark Triad manifest similarly in men and women?: Measurement invariance of the Dirty Dozen across sex

The Dark Triad is a constellation of three socially undesirable personality traits: narcissism, psychopathy, and Machiavellianism. Previous research has shown that men tend to score higher than women on Dark Triad scales, but the validity of these results is questionable as there is no evidence that the scales used exhibit measurement invariance across sex in the adult population. Here, we report four studies assessing the measurement invariance across sex of a recently developed, concise measure of the Dark Triad, namely Jonason and Webster's (2010) Dirty Dozen (DD). As no validated Italian version of the DD was available, we developed an Italian version and assessed its psychometric properties. Studies 1 to 3 revealed that the Italian DD had adequate psychometric properties, and replicated the three-factor structure and the nomological network of the original version. Study 4 provided evidence of the measurement invariance of the DD across sex, such that men scored higher than women with respect to psychopathy, Machiavellianism, and, to a lesser extent, narcissism. These findings indicate that the DD can be used to provide reliable assessments of sex differences in Dark Triad traits. Furthermore, the results of sex comparisons are consistent with a biosocial approach to social role theory that assumes that being agentic rather than communal is considered desirable for men and undesirable for women