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To compare comorbidities in a cohort of cyclic citrullinated peptide (CCP) antibody positive patients without or prior to onset of inflammatory arthritis (IA) to those in patients with early IA. Baseline data from two established cohorts were used. The first recruited people at risk of IA: CCP antibody positive cases without IA (CCP Cohort,  = 296). The second cohort [the Inflammatory Arthritis CONtinuum study (IACON)] recruited patients with early IA (  = 725). Proportions of patients with given comorbidities were compared between cohorts and then logistic regression was used to determine odds ratios (OR) for the CCP cohort having specific comorbidities, compared to IACON patients. Analyses adjusted for gender, age, smoking status, and body mass index. Patients from the CCP cohort were younger (mean age 50, compared to 53 years). The proportion of patients with at least one comorbidity was higher in the IACON than the CCP cohort: (40% compared to 24%, respectively). Results of logistic regression analyses suggested the odds of hypertension, taking a lipid-lowering agent, ischemic heart disease, cerebrovascular disease, lung disease, and diabetes were not increased in either cohort. However, patients in the CCP cohort were more likely to be taking an antidepressant (OR = 1.62, 95% CI 1.03, 2.56,  = 0.037). There was no significant difference in comorbidities among people with CCP antibodies but without IA, compared to those of patients with established IA.

This report on voice and agency, which builds on the 2012 World Development Report, focuses on several areas key to women's empowerment: freedom from violence, control over sexual and reproductive health and rights, ownership and control of land and housing, and voice and collective action. It explores the power of social norms in dictating how men and women can and cannot behave, deterring women from owning property or working even where laws permit, for example, because those who do become outcasts. The report distills vast data and hundreds of studies to shed new light on constraints facing women and girls worldwide, from epidemic levels of gender-based violence to biased laws and norms that prevent them from owning property, working, and making decisions about their own lives. It highlights promising reforms and interventions from around the world and lays out an urgent agenda for governments, civil society, development agencies, and other stakeholders. Among its keys findings: girls with little or no education are far more likely to be married as children, suffer domestic violence, live in poverty, and lack a say over household spending or their own health care than better-educated peers, which harms them, their children, and communities.

Methotrexate (MTX) monotherapy is a common first treatment for rheumatoid arthritis (RA), but many patients do not respond adequately. In order to identify genetic predictors of response, we have combined data from two consortia to carry out a genome-wide study of response to MTX in 1424 early RA patients of European ancestry. Clinical endpoints were change from baseline to 6 months after starting treatment in swollen 28-joint count, tender 28-joint count, C-reactive protein and the overall 3-component disease activity score (DAS28). No single nucleotide polymorphism (SNP) reached genome-wide statistical significance for any outcome measure. The strongest evidence for association was with rs168201 in NRG3 (p = 10−7 for change in DAS28). Some support was also seen for association with ZMIZ1, previously highlighted in a study of response to MTX in juvenile idiopathic arthritis. Follow-up in two smaller cohorts of 429 and 177 RA patients did not support these findings, although these cohorts were more heterogeneous.

We have discovered an antifreeze protein in an overwintering perennial ryegrass, Lolium perenne. The protein is stable at 100 degree C and although it is a less effective antifreeze than proteins found in antarctic fish and insects, it is better at preventing ice recrystallization. This property enables grasses to tolerate ice formation in their tissues without being damaged, suggesting that the control of ice-crystal growth rather than the prevention of freezing may have evolved to be the critical factor in their survival at very low temperatures.

We have discovered an antifreeze protein in an overwintering perennial ryegrass, Lolium perenne. The protein is stable at 100 °C and although it is a less effective antifreeze than proteins found in antarctic fish and insects, it is better at preventing ice recrystallization. This property enables grasses to tolerate ice formation in their tissues without being damaged, suggesting that the control of ice-crystal growth rather than the prevention of freezing may have evolved to be the critical factor in their survival at very low temperatures.

Objectives The aims of this study were to assess the association between area-level socio-economic deprivation and the phenotype of rheumatoid arthritis (RA), defined by rheumatoid factor (RF) and anticitrullinated peptide antibody (AC PA) status, and to determine whether any observed association can be explained by smoking. Methods The authors performed logistic regression analysis of 6298 patients with RA, defined by American College of Rheumatology classification criteria modified for genetic studies. Analysis was stratified by cohort/recruitment centre. Socio-economic deprivation was measured using the Townsend Index. Results Deprivation predicted RF but not ACPA positivity, independent of smoking. The ORs for trend across tertiles, adjusted for smoking, gender, period of birth and cohort/recruitment centre, were 1.14 (95% CI 1.01 to 1.29) for RF and 1.01 (95% CI 0.87 to 1.16) for ACPA. Even after adjusting for deprivation, smoking was strongly associated with ACPA positivity (OR 1.38, 95% CI 1.22 to 1.55). There was no evidence of any effect modification by the RA risk alleles (HLA-DRB1 shared epitope and PTPN22 rs2476601) that have previously been shown to modify the effect of smoking on ACPA and RF positivity. Conclusions Among patients with RA, deprivation predicted RF positivity but not ACPA positivity. The effect of deprivation did not appear to be explained by smoking. Deprivation may be a marker for previously unrecognised, potentially modifiable environmental influences on the immunological phenotype of RA. Furthermore, given the known associations of RF positivity with prognosis and response to treatment in RA, these findings have potential implications for resource allocation and healthcare delivery.

Saddle-nose deformity can occur as a result of trauma to the nose, but it has also been well described in the setting of infections such as leprosy and syphilis and idiopathic inflammatory conditions such as granulomatosis with polyangiitis (formerly known as Wegener granulomatosis) and relapsing polychondritis. Since these deformities may also arise without an evident precipitating cause, they can pose a diagnostic conundrum. We review 2 cases of saddle-nose deformity that were treated at Northwick Park Hospital in Middlesex, England. The first patient was a 53-year-old woman who presented with epistaxis and deviation of the nasal septum. She subsequently developed a saddle-nose deformity and a septal ulcer. An autoimmune screen was negative, and histologic findings were nonspecific. She underwent successful reconstruction with a polyethylene implant. The second patient was a 21-year-old woman who presented with nasal obstruction and a nasal septal deviation. Two years later, she was diagnosed with Crohn disease and treatment with azathioprine was commenced. Eventually, the cartilaginous dorsum of her nose collapsed. A biopsy of the area revealed nonspecific, active, chronic inflammation. A polyethylene implant was placed to correct the deformity, but part of the implant became dislodged, and revision surgery was not successful. A subsequent revision was performed, and the early results were encouraging. Saddle-nose deformity may be a manifestation of underlying connective tissue disease, so it is important to detect and treat any such condition before embarking on surgical repair of the deformity. Our 2 cases indicate that this very deforming condition is poorly understood and treatment can be unsatisfactory.

Objective: The aim was to study the course of disease activity and disability in early rheumatoid arthritis (RA) and the relationship between the two over 24 months. Baseline predictors of adverse outcome were sought as potential tools for targeting future therapy in RA. Methods: Yorkshire Early Arthritis Register (YEAR) recruited patients with a clinician-made diagnosis of RA and symptoms of ≤24 months. Change in disease activity, measured using disease activity score from counts of 28 joints (DAS28) and disability, measured using the disability index component of the health assessment questionnaire (HAQ-DI), after 6 and 12 months, were outcomes in linear regression models. In order to take advantage of the longitudinal data and examine change in DAS28 and HAQ-DI over time, latent growth curves were applied to the data. Latent class growth analyses (LCGA) identified trajectories of change in DAS28 and HAQ-DI over 2 years. Multinomial logistic regression identified predictors of trajectory group membership. Finally, a dual trajectory analysis explored the relationship between DAS28 and HAQ-DI trajectories. Missing data were handled using multiple imputation and maximum likelihood estimation. Results: Data from 1416 YEAR cases were included. Baseline fatigue visual analogue score (VAS) consistently predicted worse outcome including lesser change in DAS28 and HAQ-DI after 6 and 12 months and adverse DAS28 and HAQ-DI trajectories. There were 2 DAS28 and 2 HAQ-DI trajectories and 4 dual trajectory groups: half of patients followed the most favourable, low DAS28/low HAQ-DI, trajectory and only 1% followed a high DAS28/low HAQ-DI trajectory. High DAS28/high HAQ-DI and low DAS28/high HAQ-DI trajectories were more likely for females, cases from more deprived socio-economic areas, and those reporting greater fatigue at baseline. The high DAS28/high HAQ-DI trajectory was more likely in cases with higher baseline DAS28, but baseline DAS28 did not predict low DAS28/high HAQ-DI trajectory group membership. Membership of the low DAS28/high HAQ-DI group was more likely in cases with greater contribution of subjective components to baseline DAS28 . Conclusion: Baseline fatigue consistently predicted adverse DAS28 and HAQ-DI over 2 years. In some cases, there was persistent disability and disease activity, whilst another group had greater disability despite less disease activity. Compared to those with low disease activity and disability, membership of these 2 groups was more likely with greater baseline fatigue. Further research into the drivers of fatigue in RA may help target therapies and limit disability in RA.

To date, functional MTHFR SNPs have been tested for their impact on low-dose methotrexate (MTX) response in small rheumatoid arthritis (RA) cohorts. We sought to test their effect in the single largest cohort studied to date, and undertook a meta-analysis utilizing stringent study inclusion criteria. RA patients treated with MTX monotherapy from the Yorkshire Early Arthritis Register (YEAR) were genotyped using RFLP assays, and tested for association with treatment efficacy. Studies for meta-analysis were screened by a set of stringent inclusion criteria. rs1801131 and rs1801133 were not associated with response to MTX in the YEAR cohort, nor did they affect the probability of achieving a low disease activity state. A meta-analysis of comparable studies found no association with these SNPs. MTHFR SNPs rs1801131 and rs1801133 are unlikely to have a clinically meaningful effect on the first 6 months of MTX treatment in early RA.