A thematic analysis of alcohol use and culture amongst elite (intercounty) Gaelic Athletic Association (GAA) players.

BACKGROUND: There are limited studies examining alcohol consumption in Gaelic Athletic Association (GAA) players. In a previous paper, we reported excess alcohol consumption, alcohol-related harms and binge drinking amongst elite GAA players. In that survey, the players were provided with an opportunity to provide comments on alcohol. This current study analyses these comments. AIMS: The aim of this study was to provide a qualitative analysis of elite GAA players opinions on alcohol consumption, harms, behaviours and culture. METHODS: An anonymous, web-based e-questionnaire was distributed to all registered adult elite (inter-county) GAA players. This analysed demographics, alcohol consumption, alcohol culture and alcohol-related harms. This paper is a thematic analysis of the players comments on alcohol in the GAA. RESULTS: Seven hundred seventy-three of 3592 (21%) players responded. One hundred fifty-two respondents (21%) commented in the free text section of the survey regarding alcohol. One hundred eleven comments (73%) were suitable for analysis. Relevant themes were a pattern of abstinence and bingeing (n = 44), excess alcohol consumption (n = 40) and drinking bans contributing to a binge drinking culture (n = 37). There was a mixed attitude to alcohol sponsorship. CONCLUSION: These data show players recognise intermittent binge drinking with periods of abstinence and alcohol-related harms. Further initiatives regarding alcohol harm reduction merit consideration including prohibition of alcohol sponsorship, similar to the GAA's ban on gambling.

Non-pharmacological interventions in the treatment of rheumatoid arthritis: A systematic review and meta-analysis.

PURPOSE: To investigate the role of non-pharmaceutical therapies on disease activity in rheumatoid arthritis through systematic review and meta-analysis. METHODS: A review of Pubmed, EMBASE, Web of Science, and the Cochrane Library was performed from inception until March 26, 2019. Only randomized controlled trials which assessed oral, non-pharmacological interventions (e.g. diets, vitamins, oils, herbal remedies, fatty acids, supplements, etc.) in adult patients with rheumatoid arthritis, that presented clinically-relevant outcomes (defined as pain, fatigue, disability, joint counts, and/or disease indices) were included in our meta-analysis. Data were analyzed as mean differences between active and placebo and forest plots were performed. Heterogeneity was evaluated using I-squared statistics while funnel plots and Cochrane's risk of bias assessment evaluated bias. RESULTS: 8170 articles were identified in the search and 51 were RCTs were included. The mean difference in DAS28 was significantly improved in experimental group treated with diet (-0.46 [-0.91, -0.02], p = 0.04), zinc sulfate, copper sulphate, selenium, potassium, lipoic acid, turmeric, pomegranate extract, chamomile, and cranberry extract supplements (-0.77 [-1.17, -0.38], p < 0.001), A, B6, C, D, E, and K vitamins (-0.52 [-0.74, -0.29], p < 0.001), and fatty acids (-0.19 [-0.36, -0.01], p = 0.03). Other clinical metrics such as SJC, TJC, HAQ, SDAI, ACR20, and self-reported pain were decreased in the treatment groups. There was significant reporting bias in the studies. CONCLUSION: Some non-pharmacological therapies may modestly improve some clinical outcomes in patients with rheumatoid arthritis. Many identified studies lacked full reporting. Further clinical trials that are well-designed, adequately powered, and sufficiently report ACR improvement criteria or EULAR response criteria outcomes are needed to confirm the efficacy of these therapies.

Predictors of adverse gambling behaviours amongst elite athletes.

Problem gambling levels amongst elite sportspeople are above populational baseline. We assess gambling in an elite Irish sporting population. An anonymous web-based questionnaire including the validated Problem Gambling Severity Index was distributed. Univariate and multivariate analyses were performed to evaluate predictors of moderate/high risk gambling. 608 players (mean age 24) were included. Seventy nine percent of respondents were current gamblers and 6% problem gamblers. Amongst high-risk gamblers, significantly more were male (100% vs 76%, p = 0.003), fewer completed university (52% vs 69%, p = 0.024), and more were smokers (48% vs 24%, p = 0.002). They were also more likely to avail of free online gambling offers (90% vs 44%, p < 0.001), gamble with teammates (52% vs 21%, p < 0.001) and have placed their first bet before age 16 (41% vs 19%, p = 0.003). In multivariate analysis, moderate/high risk gambling was associated with: male gender (OR = 8.9 [1.1-69], p = 0.035), no 3rd level education (OR = 2.5 [1.4-5.0], p = 0.002), free online gambling use (OR = 4.3 [2.1-5.3], p < 0.001), gambling with teammates (OR = 3.0 [1.7-5.3], p < 0.001), and being under 18 at first bet (OR = 2.0 [1.1-3.3], p = 0.013). This study shows a harmful gambling culture amongst elite Irish athletes. Male gender, lower educational status, free online gambling use, gambling with teammates and first bet at less than age 18 were associated with moderate/high risk gambling. These groups may benefit from targeted interventions.

miRNA-Dependent Regulation of AKT1 Phosphorylation.

The phosphoinositide-3-kinase (PI3K)/AKT pathway regulates cell survival and is over-activated in most human cancers, including ovarian cancer. Following growth factor stimulation, AKT1 is activated by phosphorylation at T308 and S473. Disruption of the AKT1 signaling pathway is sufficient to inhibit the epithelial-mesenchymal transition in epithelial ovarian cancer (EOC) cells. In metastatic disease, adherent EOC cells transition to a dormant spheroid state, characterized previously by low S473 phosphorylation in AKT1. We confirmed this finding and observed that T308 phosphorylation was yet further reduced in EOC spheroids and that the transition from adherent to spheroid growth is accompanied by significantly increased levels of let-7 miRNAs. We then used mechanistic studies to investigate the impact of let-7 miRNAs on AKT1 phosphorylation status and activity in cells. In growth factor-stimulated HEK 293T cells supplemented with let-7a, we found increased phosphorylation of AKT1 at T308, decreased phosphorylation at S473, and enhanced downstream AKT1 substrate GSK-3ß phosphorylation. Let-7b and let-7g also deregulated AKT signaling by rendering AKT1 insensitive to growth factor simulation. We uncovered let-7a-dependent deregulation of PI3K pathway components, including PI3KC2A, PDK1, and RICTOR, that govern AKT1 phosphorylation and activity. Together, our data show a new role for miRNAs in regulating AKT signaling.

Ocular manifestations of Behçet's disease in children and adults: a systematic review and meta-analysis.

OBJECTIVES: Children and adults may develop Behçet's disease (BD), often with ocular involvement such as uveitis. This study aimed to determine the prevalence and type of ocular manifestations in childhood and adult BD. METHODS: Medline, Web of Science and Cochrane databases were searched from inception to October 5, 2018 to identify publications related to Behçet's disease comprising minimum twenty patients and providing the frequency of ocular manifestations (OC). Random effects models were used to combine the prevalence of OC in adults and children with BD. Heterogeneity was evaluated using I2. RESULTS: The search resulted in 3129 articles, of which 51 were included in meta-analysis. OCs were slightly more frequent in childhood onset BD with the mean [95% Confidence Interval] frequency of 45 [34-56%] compared to 36 [29-43%] in adults, however, this difference was not statistically significant (p=0.198). In both children and adults, posterior uveitis (children 27% vs. adults 25%, and retinal vasculitis in adults 16%) was the most common ocular manifestation, followed by anterior uveitis (children 18% vs. adults 23%). When comparing the distribution of OC in Behcet's in adults, there was geographic variation where OC were higher in Turkey and the Middle East 42%, followed by Europe and North America (36%), North Africa 26% and East Asia 25% but not significantly (p=0.27). CONCLUSIONS: Ocular manifestations, predominantly uveitis; are common in BD. Ocular manifestations are not proportionately more frequent in adults with BD along the ancient Silk Road.

Exploring the effect of alcohol on disease activity and outcomes in rheumatoid arthritis through systematic review and meta-analysis.

To evaluate the effects of alcohol consumption on disease activity in rheumatoid arthritis. EMBASE, Pubmed, the Cochrane Library, and Web of Science were searched until July 29, 2020. English language studies that reported disease activity outcomes in rheumatoid arthritis were included. Studies were excluded if they were reviews, case reports, had fewer than 20 patients, or reported on prevalence but not disease activity in RA. Forest plots were used to determine pooled mean difference and were generated on RevMan5.3. Linear regression was used to determine correlations between alcohol and antibody status, gender, and smoking status. The search identified 4126 citations of which 14 were included. The pooled mean difference in DAS28 (95% CI) was 0.34 (0.24, 0.44) (p < 10-5) between drinkers and non-drinkers with lower DAS28 in non-drinkers, 0.33 (0.05, 0.62) (p = 0.02) between heavy drinkers and non-drinkers with lower DAS28 in heavy drinkers, and 0.00 (- 0.30, 0.30) (p = 0.98) between low- and high-risk drinkers. The mean difference of HAQ assessments was significantly different between those who drink alcohol compared to those who do not, with drinkers reporting lower HAQ scores (0.3 (0.18, 0.41), p < 10-5). There was no significant correlation between drinking and gender, smoking status, or antibody positivity. Alcohol consumption is associated with lower disease activity and self-reported health assessment in rheumatoid arthritis. However, drinking has no correlation with smoking, gender, or antibody status.

Systematic Analysis of the Literature in Search of Defining Systemic Sclerosis Subsets.

OBJECTIVE: Systemic sclerosis (SSc) is a multisystem disease with heterogeneity in presentation and prognosis.An international collaboration to develop new SSc subset criteria is underway. Our objectives were to identify systems of SSc subset classification and synthesize novel concepts to inform development of new criteria. METHODS: Medline, Cochrane MEDLINE, the Cumulative Index to Nursing and Allied Health Literature, EMBASE, and Web of Science were searched from their inceptions to December 2019 for studies related to SSc subclassification, limited to humans and without language or sample size restrictions. RESULTS: Of 5686 citations, 102 studies reported original data on SSc subsets. Subset classification systems relied on extent of skin involvement and/or SSc-specific autoantibodies (n = 61), nailfold capillary patterns (n = 29), and molecular, genomic, and cellular patterns (n = 12). While some systems of subset classification confer prognostic value for clinical phenotype, severity, and mortality, only subsetting by gene expression signatures in tissue samples has been associated with response to therapy. CONCLUSION: Subsetting on extent of skin involvement remains important. Novel disease attributes including SSc-specific autoantibodies, nailfold capillary patterns, and tissue gene expression signatures have been proposed as innovative means of SSc subsetting.

The effects of alcohol consumption and its associations with disease activity among 979 patients with inflammatory arthritis.

OBJECTIVE: The role of alcohol in inflammatory disease remains debated. This study explores the relationship between alcohol and disease activity in patients with inflammatory arthritis. METHODS: Patients attending a rheumatology clinic between 2010 and 2020 were prospectively followed. Information on demographics, alcohol use, smoking habits and disease outcome measures were collected from these patients. Statistical analysis included univariate and multivariate linear and binary logistic regressions, Mann-Whitney U tests and one-way analysis of variance with Tukey's honest significant difference (HSD) test. RESULTS: Of the 979 analysed patients, 62% had rheumatoid arthritis (RA), 26.7% had psoriatic arthritis (PsA) and 11.2% had ankylosing spondylitis. Mean DAS28-CRP (Disease Activity Score 28 - C-reactive protein) in RA and PsA at 1 year was 2.96±1.39, and 64.2% of patients were in remission (DAS28-CRP ≤2.6 or BASDAI (Bath Ankylosing Spondylitis Disease Activity Index) ≤4). Both male gender and risky drinking (>15 units of weekly alcohol) were significantly associated with remission. Compared with women, men had an OR of 1.8 (1.1, 2.5) (p=0.034) for any alcohol consumption and 6.9 (4.7, 9.1) (p=0.001) for drinking at least 15 weekly drinks. When adjusted for gender, there was no association between alcohol and disease activity. Yet, when adjusted for alcohol consumption, gender still significantly influenced disease activity. CONCLUSION: While it may appear that alcohol is linked to remission in inflammatory arthritis, when adjusted for gender, it is not. Men with inflammatory arthritis drink significantly more than women and have less severe disease activity.

A meta-analysis of the epidemiology of giant cell arteritis across time and space.

INTRODUCTION: Giant cell arteritis (GCA) is a common large vessel vasculitis in those over age 50 years. This meta-analysis examined the geographical and temporal distribution of the incidence, prevalence, and mortality of GCA. METHODS: A systematic review was conducted using EMBASE, Scopus, and PubMed from their inceptions until 2019. Studies were included if they reported at least 50 or more GCA patients and defined the location and time frame. Articles on mortality were included and standardized mortality ratio (SMR) was extracted where possible. Mean pooled prevalence, incidence, and SMR were calculated using a random effects model. Linear regression was used to explore correlations between latitude and incidence, prevalence, and mortality. RESULTS: Of the 3569 citations identified, 107 were included. The pooled incidence of GCA was 10.00 [9.22, 10.78] cases per 100,000 people over 50 years old. This incidence was highest in Scandinavia 21.57 [18.90, 24.23], followed by North and South America 10.89 [8.78, 13.00], Europe 7.26 [6.05, 8.47], and Oceania 7.85 [- 1.48, 17.19]. Pooled prevalence was 51.74 [42.04, 61.43] cases per 100,000 people over age 50. Annual mortality was 20.44 [17.84, 23.03] deaths/1000. Mortality generally decreased over the years of publication (p = 0.0008). Latitude correlated significantly with incidence (p = 0.0011), but not with prevalence, or mortality. CONCLUSIONS: GCA incidence varies nearly 3-fold between regions and is highest in Scandinavia but not significantly. Mortality may be improving over time.

Long-term remission and biologic persistence rates: 12-year real-world data.

BACKGROUND: Biologic therapies have greatly improved outcomes in rheumatoid arthritis (RA) and psoriatic arthritis (PsA). Yet, our ability to predict long-term remission and persistence or continuation of therapy remains limited. This study explores predictors of remission and persistence of the initial biologic therapy in patients after 12 years. Furthermore, outcomes with adalimumab and etanercept are compared. PATIENTS AND METHODS: RA and PsA patients were prospectively recruited from a biologic clinic. Outcomes on commencing therapy, at 1 year and 12 years were reviewed. Demographics, medications, morning stiffness, patient global health score, tender and swollen joint counts, antibody status, CRP and HAQ were collected. Outcomes at 1 year and 12 years are reported and predictors of biologic persistence and EULAR-defined remission (DAS28-CRP < 2.6) are examined with univariate and multivariate analysis. RESULTS: A total of 403 patients (274 RA and 129 PsA) were analysed. PsA patients were more likely to be male, in full-time employment and have completed higher education. PsA had higher remission rates than RA at both 1 year (60.3% versus 34.5%, p < 0.001) and 12 years (91.3% versus 60.6%, p < 0.001). This difference persisted when patients were matched for baseline disease activity (p < 0.001). Biologic continuation rates were high for RA and PsA at 1 year (49.6% versus 58.9%) and 12 years (38.2% versus 52.3%). In PsA, patients starting on etanercept had lower CRP at 12 years (p = 0.041). Multivariate analysis showed 1-year continuation [OR 4.28 (1.28-14.38)] and 1-year low-disease activity [OR 3.90 (95% CI 1.05-14.53)] was predictive of a 12-year persistence. Persistence with initial biologic at 12 years [OR 4.98 (95% CI 1.83-13.56)] and male gender [OR 4.48 (95% CI 1.25-16.01)] predicted 12 year remission. CONCLUSIONS: This is the first study to show better response to biologic therapy in PsA compared to RA at 12 years. Long-term persistence with initial biologic agent was high and was predicted by biologic persistence and low-disease activity at 1 year. Interestingly, PsA patients had higher levels of employment, educational attainment, and long-term remission rates compared to RA patients.

Ocular Manifestations in Rheumatoid Arthritis, Connective Tissue Disease, and Vasculitis: A Systematic Review and Metaanalysis.

OBJECTIVE: Rheumatoid arthritis (RA) and other rheumatic diseases may present with ocular manifestations.The purpose of our work was to determine the prevalence and type of eye involvement in RA and other connective tissue diseases through a metaanalysis and literature review. METHODS: A systematic review of the literature was performed using Medline, Web of Science, and the Cochrane Library from their inceptions until January 7, 2019. Conjunctivitis, keratoconjunctivitis sicca, xeropthalmia, uveitis, eye hemorrhage, optic neuritis, papilledema, orbital disease, retinal artery/vein occlusion, macular edema, retinitis, chorioretinitis, scleritis, iridocyclitits, choroid hemorrhage, blindness, and amaurosis fugax were searched for prevalence in patients with RA, systemic lupus erythematosus (SLE), antiphospholipid syndrome (APS), dermatomyositis, polymyositis, systemic sclerosis, Sjögren syndrome (SS), undifferentiated connective tissue disease, giant cell arteritis, granulomatosis polyangiitis (GPA; formerly Wegener granulomatosis), systemic vasculitis, and sarcoidosis. RESULTS: There were 3394 studies identified and 65 included. The prevalence of eye involvement was 18% in RA, 26% in GPA, 27% in giant cell arteritis, 27% in sarcoidosis, 31% in SLE, and 35% in APS. The most common manifestation was dry eye syndrome ("dry eye"; keratoconjunctivitis sicca) in most diseases analyzed, with an especially high frequency of 89% in SS. Anterior and posterior uveitis were the most common ocular complications in sarcoidosis, occurring in 16% (95% CI 3-28) and 6% (95% CI 3-9) of patients, respectively. CONCLUSION: Eye involvement is present in approximately one-fifth of patients with RA, and a one-quarter to one-third of patients with connective tissue diseases (other than SS at 89%) and vasculitis.

COVID-19 and rheumatic musculoskeletal disease patients: infection rates, attitudes and medication adherence in an Irish population.

OBJECTIVES: To establish, amongst Irish rheumatic musculoskeletal disease (RMD) patients, rates of COVID-19 symptoms and positive tests, DMARD adherence and attitudes to virtual clinics. METHODS: An online survey assessing COVID-19 status, RMD diagnoses, adherence and information sources was disseminated via the Arthritis Ireland website and social media channels. RESULTS: There were 1381 respondents with 74.8% on immunosuppressive medication. Symptoms of COVID-19 were reported by 3.7% of respondents of which 0.46% tested positive, consistent with the general Irish population. The frequency of COVID-19 symptoms was higher for respondents with spondyloarthropathy [odds ratio (OR) 2.06, 95% CI: 1.14, 3.70] and lower in those on immunosuppressive medication (OR 0.48, 95% CI: 0.27, 0.88), and those compliant with health authority (HSE) guidance (OR 0.47, 95% CI: 0.25, 0.89). Adherence to RMD medications was reported in 84.1%, with 57.1% using health authority guidelines for information on medication use. Importantly, adherence rates were higher amongst those who cited guidelines (89.3% vs 79.9%, P <0.001), and conversely lower in those with COVID-19 symptoms (64.0% vs 85.1%, P =0.009). Finally, the use of virtual clinics was supported by 70.4% of respondents. CONCLUSION: The rate of COVID-19 positivity in RMD patients was similar to the general population. COVID-19 symptoms were lower amongst respondents on immunosuppressive medication and those adherent to medication guidelines. Respondents were supportive of HSE advice and virtual clinics.

Guidelines on prescribing and monitoring antimalarials in rheumatic diseases: a systematic review.

OBJECTIVES: The purpose of this systematic review was to identify existing guidelines for antimalarial prescribing and monitoring, specifically for hydroxychloroquine, and how these guidelines compare and have evolved over time. METHODS: A literature search was conducted using Embase and Medline to identify guidelines published from 1946-2018. MeSH terms were used and alternative spelling and related words were entered as keywords to broaden results. RESULTS: 243 results were reviewed to obtain 11 recommendations. Ophthalmology sources included the American Academy of Ophthalmology, Royal College of Ophthalmologists and Canadian editorials. The American College of Rheumatology and Canadian Rheumatology Association consensus statements summarised rheumatology recommendations. Recently, American and British guidelines changed from suggesting hydroxychloroquine doses ≤6.5 mg/kg/day to ≤5 mg/kg/day. American guidelines recommended baseline visual field (VF) testing and annual screening after five years. Visual field (VF) testing evolved from the Amsler grid to current recommendations of 10-2 automated VF and spectral-domain optical coherence tomography (SD-OCT). The 2012 Canadian recommendations suggested initial VF testing every two years, with SD-OCT after 10 years. Older British guidelines advocated for baseline and annual assessment with Amsler grids during rheumatology clinic visits. The 2018 British guidelines supported baseline and annual screening after five years with 10-2 VF, SD-OCT and fundus autofluorescence. CONCLUSIONS: The newest recommendations are heterogeneous suggesting lower hydroxychloroquine dosing. Retinal toxicity is irreversible and the risk increases over time. Annual screening after five years with automated VF and SD-OCT may be warranted to detect early changes and discontinue therapy if necessary.

The challenges of theory-software translation.

Background: Software is now ubiquitous within research. In addition to the general challenges common to all software development projects, research software must also represent, manipulate, and provide data for complex theoretical constructs. Ensuring this process of theory-software translation is robust is essential to maintaining the integrity of the science resulting from it, and yet there has been little formal recognition or exploration of the challenges associated with it. Methods: We thematically analyse the outputs of the discussion sessions at the Theory-Software Translation Workshop 2019, where academic researchers and research software engineers from a variety of domains, and with particular expertise in high performance computing, explored the process of translating between scientific theory and software. Results: We identify a wide range of challenges to implementing scientific theory in research software and using the resulting data and models for the advancement of knowledge. We categorise these within the emergent themes of design, infrastructure, and culture, and map them to associated research questions. Conclusions: Systematically investigating how software is constructed and its outputs used within science has the potential to improve the robustness of research software and accelerate progress in its development. We propose that this issue be examined within a new research area of theory-software translation, which would aim to significantly advance both knowledge and scientific practice.

The frequency of uveitis in patients with adult versus childhood spondyloarthritis.

OBJECTIVES: This meta-analysis investigated the frequency of ocular involvement in childhood and adult spondyloarthritis (SpA). METHODS: A systematic review of the literature was conducted. Medline, Web of Science and Cochrane databases were searched upto October 2018 identifying publications related to SpA, including ankylosing spondylitis (AS) with ocular conditions (OC) (uveitis, iritis, retinitis, chorioretinitis and other ocular involvement). The rates of OC were extracted and random effects models estimated their frequency. Heterogeneity was evaluated using I2. Inclusion criteria were studies in SpA of either children or adults who included a frequency of OC. RESULTS: 3164 studies were identified, and 41 analysed which included frequencies of uveitis/iritis. Other OC were too infrequent to analyse. A pooled random effects model showed that the prevalence of uveitis was 24% in adult AS (23 studies, 11 943 patients), 10% in adult psoriatic arthritis (PsA) (9 studies, 1817) and 17% in undifferentiated adult SpA (9 studies, 6568 patients). In juveniles with AS, the prevalence of uveitis was 27% (8 studies, 927 patients), in juvenile PsA it was 16% (5 studies, N=498) and in juvenile undifferentiated SpA, uveitis occurred in 7% (2 studies, 1531 patients). In all evaluated SpA subgroups, there were no statistical differences in the frequency of uveitis between juveniles and adults. CONCLUSIONS: Uveitis in adult versus child-onset SpA is similar in AS but more common in adult-onset undifferentiated SpA, and less frequent in adult-onset PsA compared to child-onset PsA, but the differences were not significant.

Factors associated with pulmonary arterial hypertension (PAH) in systemic sclerosis (SSc).

BACKGROUND: Pulmonary arterial hypertension (PAH) in systemic sclerosis (SSc) is a lethal complication affecting 8-15% of patients. Screening tests such as echocardiography and pulmonary function tests allow for triaging patients for diagnosis by right heart catheterization. Understanding risk factors of SSc-PAH could help differentiate high-risk patients. METHODS: A systematic review was conducted to determine associations with SSc-PAH, including clinical/disease characteristics, antibodies, labs and biomarkers. The frequencies of publications featuring each risk/association were reported. RESULTS: Among 2654 articles, 984 duplicates and 1578 irrelevant articles were removed, leaving 92 articles for manual screening. After excluding 55 papers with small sample sizes, publications from identical cohorts, not English language, or PAH not ascertained by RHC, 37 articles were eligible. A total of 43 factors for SSc-PAH were identified within seven categories. Several associations were due to PAH and risk factors such as dynpnea, right heart failure, and short 6-minute walk distance. Patient characteristics (14), pulmonary physiology (6), antibody profiles (6) and genetics/epigenetics (6) had the most numerous and diverse factors, while biomarkers (4) and other labs (2) features were infrequent. Low carbon monoxide (DLCO) (6), older age (4), longer disease duration (4), positive anticentromere antibodies (ACA) (4), telangiectasias (4), high brain natriuretic peptide (4) were frequent associations. CONCLUSIONS: Risk factors for SSc-PAH such as ACA, older age, longer disease duration limited cutaneous SSc subset and presence of ILD may enrich screening programs. Genes and other antibody profiles are inconsistent and requires further validation.

Multiscale computational models can guide experimentation and targeted measurements for crop improvement.

Computational models of plants have identified gaps in our understanding of biological systems, and have revealed ways to optimize cellular processes or organ-level architecture to increase productivity. Thus, computational models are learning tools that help direct experimentation and measurements. Models are simplifications of complex systems, and often simulate specific processes at single scales (e.g. temporal, spatial, organizational, etc.). Consequently, single-scale models are unable to capture the critical cross-scale interactions that result in emergent properties of the system. In this perspective article, we contend that to accurately predict how a plant will respond in an untested environment, it is necessary to integrate mathematical models across biological scales. Computationally mimicking the flow of biological information from the genome to the phenome is an important step in discovering new experimental strategies to improve crops. A key challenge is to connect models across biological, temporal and computational (e.g. CPU versus GPU) scales, and then to visualize and interpret integrated model outputs. We address this challenge by describing the efforts of the international Crops in silico consortium.

The frequency of uveitis in patients with juvenile inflammatory rheumatic diseases.

OBJECTIVES: This meta-analysis investigated the frequency and type of ocular involvement in juvenile inflammatory arthritis (JIA) and other juvenile rheumatic diseases. METHODS: Medline, Web of Science and Cochrane databases were searched from inception to September 2018 to identify publications related to juvenile arthritis and rheumatic diseases, which reported frequency of Uveitis in juvenile rheumatic conditions and contained at least 20 patients. The prevalence and type of eye complications were extracted, and random effects models estimated their frequency. Heterogeneity was evaluated using I2. RESULTS: In total, 7132 unique citations resulted in 59 articles included. Pooled frequency of uveitis was: 24% in oligoarticular JIA, 12% in polyarticular JIA, 1% in systemic JIA, 50% in pediatric Bechet's, 9% in juvenile psoriatic arthritis, 24% in juvenile spondyloarthropathy and 5% in juvenile systemic lupus erythematosus. The most common uveitis in JIA was anterior uveitis, which occurred in 14%; also described as iridocyclitis in 10% of patients. Publication bias was negligible for all conditions except those with few reported studies (juvenile SLE and systemic JIA). Uveitis in JIA was more common in Europe (14%), North America (11%) and the Middle East (12%) than East Asia (7%) and Oceania (3%). CONCLUSIONS: Ocular involvement (mostly uveitis) in juvenile inflammatory arthritis and other pediatric rheumatic diseases varied between 3% and 50% depending on the underlying condition; and was highest in pediatric Bechet's. In JIA, the highest frequency of uveitis was in oligoarticular JIA; with anterior uveitis being the most frequent type of uveitis. There was variation geographically for uveitis in JIA.