Establishing outcome measures in early knee osteoarthritis

The classification and monitoring of individuals with early knee osteoarthritis (OA) are important considerations for the design and evaluation of therapeutic interventions and require the identification of appropriate outcome measures. Potential outcome domains to assess for early OA include patient-reported outcomes (such as pain, function and quality of life), features of clinical examination (such as joint line tenderness and crepitus), objective measures of physical function, levels of physical activity, features of imaging modalities (such as of magnetic resonance imaging) and biochemical markers in body fluid. Patient characteristics such as adiposity and biomechanics of the knee could also have relevance to the assessment of early OA. Importantly, research is needed to enable the selection of outcome measures that are feasible, reliable and validated in individuals at risk of knee OA or with early knee OA. In this Perspectives article, potential outcome measures for early symptomatic knee OA are discussed, including those measures that could be of use in clinical practice and/or the research setting

Oral abstracts 3: RA Treatment and outcomesO13. Validation of jadas in all subtypes of juvenile idiopathic arthritis in a clinical setting

Background: Juvenile Arthritis Disease Activity Score (JADAS) is a 4 variable composite disease activity (DA) score for JIA (including active 10, 27 or 71 joint count (AJC), physician global (PGA), parent/child global (PGE) and ESR). The validity of JADAS for all ILAR subtypes in the routine clinical setting is unknown. We investigated the construct validity of JADAS in the clinical setting in all subtypes of JIA through application to a prospective inception cohort of UK children presenting with new onset inflammatory arthritis. Methods: JADAS 10, 27 and 71 were determined for all children in the Childhood Arthritis Prospective Study (CAPS) with complete data available at baseline. Correlation of JADAS 10, 27 and 71 with single DA markers was determined for all subtypes. All correlations were calculated using Spearman's rank statistic. Results: 262/1238 visits had sufficient data for calculation of JADAS (1028 (83%) AJC, 744 (60%) PGA, 843 (68%) PGE and 459 (37%) ESR). Median age at disease onset was 6.0 years (IQR 2.6-10.4) and 64% were female. Correlation between JADAS 10, 27 and 71 approached 1 for all subtypes. Median JADAS 71 was 5.3 (IQR 2.2-10.1) with a significant difference between median JADAS scores between subtypes (p < 0.01). Correlation of JADAS 71 with each single marker of DA was moderate to high in the total cohort (see Table 1). Overall, correlation with AJC, PGA and PGE was moderate to high and correlation with ESR, limited JC, parental pain and CHAQ was low to moderate in the individual subtypes. Correlation coefficients in the extended oligoarticular, rheumatoid factor negative and enthesitis related subtypes were interpreted with caution in view of low numbers. Conclusions: This study adds to the body of evidence supporting the construct validity of JADAS. JADAS correlates with other measures of DA in all ILAR subtypes in the routine clinical setting. Given the high frequency of missing ESR data, it would be useful to assess the validity of JADAS without inclusion of the ESR. Disclosure statement: All authors have declared no conflicts of interest. Table 1Spearman's correlation between JADAS 71 and single markers DA by ILAR subtype ILAR Subtype Systemic onset JIA Persistent oligo JIA Extended oligo JIA Rheumatoid factor neg JIA Rheumatoid factor pos JIA Enthesitis related JIA Psoriatic JIA Undifferentiated JIA Unknown subtype Total cohort Number of children 23 111 12 57 7 9 19 7 17 262 AJC 0.54 0.67 0.53 0.75 0.53 0.34 0.59 0.81 0.37 0.59 PGA 0.63 0.69 0.25 0.73 0.14 0.05 0.50 0.83 0.56 0.64 PGE 0.51 0.68 0.83 0.61 0.41 0.69 0.71 0.9 0.48 0.61 ESR 0.28 0.31 0.35 0.4 0.6 0.85 0.43 0.7 0.5 0.53 Limited 71 JC 0.29 0.51 0.23 0.37 0.14 -0.12 0.4 0.81 0.45 0.41 Parental pain 0.23 0.62 0.03 0.57 0.41 0.69 0.7 0.79 0.42 0.53 Childhood health assessment questionnaire 0.25 0.57 -0.07 0.36 -0.47 0.84 0.37 0.8 0.66 0.4

"Looking all lost towards a Cook's guide for beauty”: the art of literature and the lessons of the guidebook in modernist writing

This article explores the impact of the guidebook, especially the Baedeker series, on modernist literary culture. It argues that the guidebook is a literary phenomenon in its own right and that, as such, it attracts special attention from those engaged in defending and/or extending the category of literature as part of a modernist agenda. In particular, modernist writers are concerned as to whether the guidebook counts as a form of literature and, if so, what this means for the more familiar forms seen in their own essays, fiction and travelogues. What might the invention of the star system to rank scenes and monuments mean for the future of art criticism? How might the guidebook help or hinder the traveller in his/her pursuit of the beautiful or the picturesque? What does recourse to the guidebook reveal about the taste and education of the traveller? And, more pointedly still, what kind and quality of writing is the guidebook itself? This article surveys the extent of modernism's interest in the guidebook, both as a noteworthy new form and as a form modernist writers adapted for use in their own books, before turning in detail to commentary on the guidebook by E.M. Forster, Ernest Hemingway, H.D. and Virginia Woolf. In conclusion, it finds that the guidebook in modernism is very rarely just that. Instead, the guidebook finds unexpected affinities with modernism in its attempt to “modernise” literature – to make it more rational, more totalising and, in the eyes of its critics, less able to discriminate.This is an Accepted Manuscript of an article published by Taylor & Francis in Studies in Travel Writing on 4th March 2015, available online: http://wwww.tandfonline.com/10.1080/13645145.2014.994924

Author Correction: Scalable and robust SARS-CoV-2 testing in an academic center.

An amendment to this paper has been published and can be accessed via a link at the top of the paper

Cohort profile: methodology and cohort characteristics of the Aotearoa New Zealand Rheumatic Heart Disease Registry

Purpose To create a cohort with high specificity for moderate and severe rheumatic heart disease (RHD) in New Zealand, not reliant on International Classification of Diseases discharge coding. To describe the demography and cardiac profile of this historical and contemporary cohort.Design and participants Retrospective identification of moderate or severe RHD with disease onset by 2019. Case identification from the following data sources: cardiac surgical databases, RHD case series, percutaneous balloon valvuloplasty databases, echocardiography databases, regional rheumatic fever registers and RHD clinic lists. The setting for this study was a high-income country with continued incidence of acute rheumatic fever (ARF).Findings to date A Registry cohort of 4959 patients was established. The initial presentation was RHD without recognised prior ARF in 41%, and ARF in 59%. Ethnicity breakdown: Māori 38%, Pacific 33.5%, European 21.9%, other 6.7%. Ethnic disparities have changed significantly over time. Prior to 1960, RHD cases were 64.3% European, 25.3% Māori and 6.7% Pacific. However, in contrast, from 2010 to 2019, RHD cases were 10.7% European, 37.4% Māori and 47.2% Pacific.Follow-up showed 32% had changed region of residence within New Zealand from their initial presentation. At least one cardiac intervention (cardiac surgery, transcatheter balloon valvuloplasty) was undertaken in 64% of the cohort at a mean age of 40 years. 19.8% of the cohort had multiple cardiac interventions. At latest follow-up, 26.9% of the cohort died. Of those alive, the mean follow-up is 20.5+19.4 years. Māori and Pacific led governance groups have been established to provide data governance and oversight for the registry.Future plans Detailed mortality and morbidity of the registry cases will be defined by linkage to New Zealand national health data collections. The contemporary cohort of the registry will be available for future studies to improve clinical management and outcomes for the 3450 individuals living with chronic RHD

Association between overweight and obesity and risk of clinically diagnosed knee, hip, and hand osteoarthritis: A population-based cohort study

Objective: Previous cohorts have reported associations between overweight/obesity and knee and hand osteoarthritis (OA). However, no data on the effect of these on the OA burden are available. We aimed to analyse the effect of overweight and obesity on the incidence of routinely diagnosed knee, hip, and hand OA.Methods:Design: population-based cohortSetting: primary care records from the SIDIAP database (&gt;5.5 million subjects) covering &gt;80% of the population of Catalonia, Spain.Participants: ?40 years old with no OA on 01/01/2006 and with body mass index (BMI) data available. Follow-up: from 01/01/2006 to 12/31/2010, loss to follow-up, or death.Measures: BMI World Health Organization categories (exposure), and incident clinical diagnoses of knee, hip, or hand OA (ICD-10 codes).Results: 1,764,061 subjects were observed for a median (inter-quartile range) of 4.45 (4.19 to 4.98) years. Incidence rates (per 1000 PY) of knee, hip and hand OA ranged from 3.7 (3.6 to 3.8), 1.7 (1.7 to 1.8) and 2.6 (2.5 to 2.7) amongst normal-weight, to 19.5 (19.1 to 19.9), 3.8 (3.7 to 4.0) and 4.0 (3.9 to 4.2) in the grade II obese respectively.Compared to normal-weight subjects, being overweight or obese increased the risk of OA at all three sites, especially at the knee: overweight and (grade I, II) obesity increased knee OA risk by a factor of 2, 3.1 and 4.7 fold respectively.Conclusions: Both overweight and obesity increase the risk of hand, hip, and knee OA, especially for the latter, with a dose-response gradient with increasing BMI

Structural and biochemical characterization of the biuret hydrolase (BiuH) from the cyanuric acid catabolism pathway of Rhizobium leguminasorum bv. viciae 3841

Biuret deamination is an essential step in cyanuric acid mineralization. In the well-studied atrazine degrading bacterium Pseudomonas sp. strain ADP, the amidase AtzE catalyzes this step. However, Rhizobium leguminosarum bv. viciae 3841 uses an unrelated cysteine hydrolase, BiuH, instead. Herein, structures of BiuH, BiuH with bound inhibitor and variants of BiuH are reported. The substrate is bound in the active site by a hydrogen bonding network that imparts high substrate specificity. The structure of the inactive Cys175Ser BiuH variant with substrate bound in the active site revealed that an active site cysteine (Cys175), aspartic acid (Asp36) and lysine (Lys142) form a catalytic triad, which is consistent with biochemical studies of BiuH variants. Finally, molecular dynamics simulations highlighted the presence of three channels from the active site to the enzyme surface: a persistent tunnel gated by residues Val218 and Gln215 forming a potential substrate channel and two smaller channels formed by Val28 and a mobile loop (including residues Phe41, Tyr47 and Met51) that may serve as channels for co-product (ammonia) or co-substrate (water)

High burden of rheumatic heart disease confirmed by echocardiography among Pacific adults living in New Zealand

Background Despite numerous echocardiographic screening studies of children in high incidence acute rheumatic fever (ARF)/rheumatic heart disease (RHD) communities, little is known about the prevalence of RHD in adults in these populations.We sought to determine the prevalence of RHD in an urban area of South Auckland, New Zealand, where previous studies had shown the prevalence of RHD in children to be around 2%.Methods A cross-sectional screening study was conducted between 2014 and 2016. Echocardiography clinics were conducted at an urban Pacific-led primary healthcare clinic in New Zealand. Eligible persons aged 16–40 years were recruited according to a stratified randomised approach. Echocardiograms were performed with a standardised image acquisition protocol and reported by cardiologists.Results There were 465 individuals who underwent echocardiograms. The overall prevalence of RHD (define and borderline) was 56 per 1000 (95% CI 36 to 78 per 1000). Definite RHD was found in 10 individuals (4 of whom were already under cardiology review at a hospital clinic) with a prevalence of 22 per 1000 (95% CI 9 to 36 per 1000). Non-rheumatic cardiac abnormalities were found in 29 individuals.Conclusions There is a high burden of both rheumatic and non-rheumatic cardiac abnormalities in this population. Rates described in New Zealand are as high as lower-middle-income countries in Africa. Addressing knowledge gaps regarding the natural history of RHD detected by echocardiography in adults is a priority issue for the international RHD community

Structure and biology of a carcinoma-associated mucin, MUC1

Although mucins have been studied at the biochemical and biophysical level for some time, attempts to define their structures in detail were only partially successful because of their size and complexity. The advent of monoclonal antibodies reactive with these molecules introduced a new approach to structural studies by defining antigenic epitopes, by allowing purification of the mucin molecules by affinity chromatography, and by providing a means to clone genes coding for the core proteins. By their profile of reactivity with the normal and cancer-associated mucin in a particular tissue, the antibodies also defined a difference in the mucin derived from the two sources. It is now clear that this difference lies in the carbohydrate side chains, as the core proteins are identical. Because the mucins are tumor-associated antigens and the cancer mucins can express epitopes that are relatively tumor specific, this family of molecules is now being intensively studied. There is also considerable interest in elucidating the normal function of the mucin and in determining whether, through an altered structure, this function is subverted in malignancy. In the next few years we should expect that the structure of other mucins will be defined in the same detail as the product of the MUC1 gene. We should also expect to see the continued application of mucin-reactive antibodies in the clinic and the investigation of mucins as agents for immunotherapy of some cancers. As to the function(s) of these molecules, perhaps we will learn enough in the future to make a critical reappraisal of the nam