Auxetic foam for snowsport safety devices

Skiing and snowboarding are popular snow-sports with inherent risk of injury. There is potential to reduce the prevalence of injuries by improving and implementing snow-sport safety devices with the application of advanced materials. This paper investigates the application of auxetic foam to snow-sport safety devices. Composite pads - consisting of foam covered with a semi-rigid shell - were investigated as a simple model of body armour and a large 70 x 355 x 355 mm auxetic foam sample was fabricated as an example crash barrier. The thermo-mechanical conversion process was applied to convert open-cell polyurethane foam to auxetic foam. The composite pad with auxetic foam absorbed around three times more energy than the conventional equivalent under quasi-static compression with a concentrated load, indicating potential for body armour applications. An adapted thermo-mechanical process - utilising through-thickness rods to control in-plane compression - was applied to fabricate the large sample with relatively consistent properties throughout, indicating further potential for fabrication of a full size auxetic crash barrier. Further work will create full size prototypes of snow-sport safety devices with comparative testing against current products

Methotrexate in rheumatoid arthritis is frequently effective, even if re-employed after a previous failure

Effectiveness of therapy with individual disease-modifying antirheumatic drugs (DMARDs) in rheumatoid arthritis (RA) is limited, and the number of available DMARDs is finite. Therefore, at some stage during the lengthy course of RA, institution of traditional DMARDs that have previously been applied may have to be reconsidered. In the present study we investigated the effectiveness of re-employed methotrexate in patients with a history of previous methotrexate failure (original course). A total of 1,490 RA patients (80% female, 59% rheumatoid factor positive) were followed from their first presentation, yielding a total of 6,470 patient-years of observation. We identified patients in whom methotrexate was re-employed after at least one intermittent course of a different DMARD. We compared reasons for discontinuation, improvement in acute phase reactants, and cumulative retention rates of methotrexate therapy between the original course of methotrexate and its re-employment. Similar analyses were peformed for other DMARDs. Methotrexate was re-employed in 86 patients. Compared with the original courses, re-employment was associated with a reduced risk for treatment termination because of ineffectiveness (P = 0.02, by McNemar test), especially if the maximum methotrexate dose of the original course had been low (<12.5 mg/week; P = 0.02, by logistic regression). In a Cox regression model, re-employed MTX was associated with a significantly reduced hazard of treatment termination compared with the original course of methotrexate, adjusting for dose and year of employment (hazard ratio 0.64, 95% confidence interval 0.42–0.97; P = 0.04). These findings were not recapitulated in analyses of re-employment of other DMARDs. Re-employment of MTX despite prior inefficacy, but not re-employment of other DMARDs, is an effective therapeutic option, especially in those patients in whom the methotrexate dose of the original course was low

Remission by composite scores in rheumatoid arthritis: are ankles and feet important?

Current treatment strategies aim to achieve clinical remission in order to prevent the long-term consequences of rheumatoid arthritis (RA). Several composite indices are available to assess remission. All of them include joint counts as the assessment of the major 'organ' involved in RA, but some employ reduced joint counts, such as the 28-joint count, which excludes ankles and feet

Sedentary behaviour is associated with increased long-term cardiovascular risk in patients with rheumatoid arthritis independently of moderate-to-vigorous physical activity

Background Rheumatoid Arthritis (RA) is associated with an increased risk of cardiovascular disease (CVD). The physical dysfunction symptomatic of RA means people living with this disease spend large periods of the day sedentary, which may further elevate their risk of CVD. The primary aim of this study was to investigate relationships between objectively assessed sedentary behaviour patterns and light physical activity (LPA) with 10-year risk of CVD. Secondary aims were to explore the role of sedentary behaviour patterns and LPA for individual CVD risk factors and functional disability in RA. The extent to which associations were independent of moderate-to-vigorous physical activity (MVPA) engagement was also examined. Methods Baseline data from a subsample of participants recruited to the Physical Activity in Rheumatoid Arthritis (PARA) study were used to answer current research questions. Sixty-one patients with RA (mean age (± SD) = 54.92 ± 12.39 years) provided a fasted blood sample and underwent physical assessments to evaluate factors associated with their cardiovascular health. Sedentary behaviour patterns (sedentary time, sedentary bouts, sedentary breaks), LPA and MVPA were measured via 7-days of accelerometry. Ten-year CVD risk was computed (Q-risk-score2), and functional disability determined via questionnaire. Results Regressions revealed significant positive associations between sedentary time and the number of sedentary bouts per day ≥20 min with 10-year CVD risk, with the reverse true for LPA participation. Associations were independent of MVPA engagement. Conclusions Promoting LPA participation and restricting sedentary bouts to <20 min may attenuate long-term CVD risk in RA, independent of MVPA engagement

Acute phase reactants add little to composite disease activity indices for rheumatoid arthritis: validation of a clinical activity score

INTRODUCTION: Frequent assessments of rheumatoid arthritis (RA) disease activity allow timely adaptation of therapy, which is essential in preventing disease progression. However, values of acute phase reactants (APRs) are needed to calculate current composite activity indices, such as the Disease Activity Score (DAS)28, the DAS28-CRP (i.e. the DAS28 using C-reactive protein instead of erythrocyte sedimentation rate) and the Simplified Disease Activity Index (SDAI). We hypothesized that APRs make limited contribution to the SDAI, and that an SDAI-modification eliminating APRs – termed the Clinical Disease Activity Index (CDAI; i.e. the sum of tender and swollen joint counts [28 joints] and patient and physician global assessments [in cm]) – would have comparable validity in clinical cohorts. METHOD: Data sources comprised an observational cohort of 767 RA patients (average disease duration 8.1 ± 10.6 years), and an independent inception cohort of 106 patients (disease duration 11.5 ± 12.5 weeks) who were followed prospectively. RESULTS: Our clinically based hypothesis was statistically supported: APRs accounted only for 15% of the DAS28, and for 5% of the SDAI and the DAS28-CRP. In both cohorts the CDAI correlated strongly with DAS28 (R = 0.89–0.90) and comparably to the correlation of SDAI with DAS28 (R = 0.90–0.91). In additional analyses, the CDAI when compared to the SDAI and the DAS28 agreed with a weighted kappa of 0.70 and 0.79, respectively, and comparably to the agreement between DAS28 and DAS28-CRP. All three scores correlated similarly with Health Assessment Questionnaire (HAQ) scores (R = 0.45–0.47). The average changes in all scores were greater in patients with better American College of Rheumatology response (P < 0.0001, analysis of variance; discriminant validity). All scores exhibited similar correlations with radiological progression (construct validity) over 3 years (R = 0.54–0.58; P < 0.0001). CONCLUSION: APRs add little information on top (and independent) of the combination of clinical variables included in the SDAI. A purely clinical score is a valid measure of disease activity and will have its greatest merits in clinical practice rather than research, where APRs are usually always available. The CDAI may facilitate immediate and consistent treatment decisions and help to improve patient outcomes in the longer term

Documentation of guideline adherence in antenatal records across maternal weight categories: a chart review.

Background Documentation in medical records fulfills key functions, including management of care, communication, quality assurance and record keeping. We sought to describe: 1) rates of standard prenatal care as documented in medical charts, and given the higher risks with excess weight, whether this documentation varied among normal weight, overweight and obese women; and 2) adherence to obesity guidelines for obese women as documented in the chart. Methods We conducted a chart review of 300 consecutive charts of women who delivered a live singleton at an academic tertiary centre from January to March 2012, computing Analysis of Variance and Chi Square tests. Results The proportion of completed fields on the mandatory antenatal forms varied from 100% (maternal age) to 52.7% (pre-pregnancy body mass index). Generally, documentation of care was similar across all weight categories for maternal and prenatal genetic screening tests, ranging from 54.0% (documentation of gonorrhea/chlamydia tests) to 85.0% (documentation of anatomy scan). Documentation of education topics varied widely, from fetal movement in almost all charts across all weight categories but discussion of preterm labour in only 20.6%, 12.7% and 13.4% of normal weight, overweight and obese women’s charts (p = 0.224). Across all weight categories, documentation of discussion of exercise, breastfeeding and pain management occurred in less than a fifth of charts. Conclusion Despite a predominance of excess weight in our region, as well as increasing perinatal risks with increasing maternal weight, weight-related issues and other elements of prenatal care were suboptimally documented across all maternal weight categories, despite an obesity guideline

Single-cell delineation of lineage and genetic identity in the mouse brain

During neurogenesis, mitotic progenitor cells lining the ventricles ofthe embryonic mouse brain undergo their final rounds of cell division, giving rise to a wide spectrum of postmitotic neurons and glia(1,2). The link between developmental lineage and cell-type diversity remains an open question. Here we used massively parallel tagging of progenitors to track clonal relationships and transcriptomic signatures during mouse forebrain development. We quantified clonal divergence and convergence across all major cell classes postnatally, and found diverse types of GABAergic neuron that share a common lineage. Divergence of GABAergic clones occurred during embryogenesis upon cell-cycle exit, suggesting that differentiation into subtypes is initiated as a lineage-dependent process at the progenitor cell level

EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2016 update

Recent insights in rheumatoid arthritis (RA) necessitated updating the European League Against Rheumatism (EULAR) RA management recommendations. A large international Task Force based decisions on evidence from 3 systematic literature reviews, developing 4 overarching principles and 12 recommendations (vs 3 and 14, respectively, in 2013). The recommendations address conventional synthetic (cs) disease-modifying antirheumatic drugs (DMARDs) (methotrexate (MTX), leflunomide, sulfasalazine); glucocorticoids (GC); biological (b) DMARDs (tumour necrosis factor (TNF)-inhibitors (adalimumab, certolizumab pegol, etanercept, golimumab, infliximab), abatacept, rituximab, tocilizumab, clazakizumab, sarilumab and sirukumab and biosimilar (bs) DMARDs) and targeted synthetic (ts) DMARDs (Janus kinase (Jak) inhibitors tofacitinib, baricitinib). Monotherapy, combination therapy, treatment strategies (treat-to-target) and the targets of sustained clinical remission (as defined by the American College of Rheumatology-(ACR)-EULAR Boolean or index criteria) or low disease activity are discussed. Cost aspects were taken into consideration. As first strategy, the Task Force recommends MTX (rapid escalation to 25 mg/week) plus short-term GC, aiming at >50% improvement within 3 and target attainment within 6 months. If this fails stratification is recommended. Without unfavourable prognostic markers, switching to—or adding—another csDMARDs (plus short-term GC) is suggested. In the presence of unfavourable prognostic markers (autoantibodies, high disease activity, early erosions, failure of 2 csDMARDs), any bDMARD (current practice) or Jak-inhibitor should be added to the csDMARD. If this fails, any other bDMARD or tsDMARD is recommended. If a patient is in sustained remission, bDMARDs can be tapered. For each recommendation, levels of evidence and Task Force agreement are provided, both mostly very high. These recommendations intend informing rheumatologists, patients, national rheumatology societies, hospital officials, social security agencies and regulators about EULAR's most recent consensus on the management of RA, aimed at attaining best outcomes with current therapies