Multilayered folding with voids

In the deformation of layered materials such as geological strata, or stacks of paper, mechanical properties compete with the geometry of layering. Smooth, rounded corners lead to voids between the layers, while close packing of the layers results in geometrically-induced curvature singularities. When voids are penalized by external pressure, the system is forced to trade off these competing effects, leading to sometimes striking periodic patterns. In this paper we construct a simple model of geometrically nonlinear multi-layered structures under axial loading and pressure confinement, with non-interpenetration conditions separating the layers. Energy minimizers are characterized as solutions of a set of fourth-order nonlinear differential equations with contact-force Lagrange multipliers, or equivalently of a fourth-order free-boundary problem. We numerically investigate the solutions of this free boundary problem, and compare them with the periodic solutions observed experimentally

Optimum fibre-steering of composite plates for buckling and manufacturability

This paper reveals the potential weight saving in creating lightweight composite panels using the novel Continous Tow Shearing technique. The method provides a unique capability to simultaneously manipulate fibre angles and local thicknesses, whilst achieving defect-free, high curvature fibre paths. Considering the buckling of a typical aircraft wing skin, the nonlinear optimisation problem presented, shows theoretical designs with significant weights savings if compared to panels made from conventional straight fibre angles (38%) or steered using Automated Fibre Placement techniques (20%). The implications due to constraints on panelstrength, damage tolerance and manufacturing costs are then considered

Characterisation of inter-ply shear in uncured carbon fibre prepreg

Understanding the inter-ply shear behaviour of uncured carbon fibre prepreg is fundamental to avoiding process-induced defects during manufacturing of large-scale components. Shear tests for AS4/8552 are compared to a one-dimensional viscoelastic–plastic model for inter-ply shear. The paper presents a methodology capable of determining the parameters of temperature, rate and pressure required for minimum resistance to movement of a prepreg. Investigating the joint strength and friction values individually shows that friction increases with temperature, contrary to previous work, and that the new value of joint strength is predominant at lower temperatures. Rate dependent variables are strongly linked to the resin behaviour, confirming the need for a viscoelastic model. Simple application to industrial scenarios is discussed along with more complex process modelling

Phase II study of docetaxel in combination with epirubicin and protracted venous infusion 5-fluorouracil (ETF) in patients with recurrent or metastatic breast cancer. A Yorkshire breast cancer research group study

This study was originally designed as a phase I/II study, with a dose escalation of docetaxel in combination with epirubicin 50 mg m⁻² and 5-fluorouracil (5-FU) 200 mg m⁻² day⁻¹. However, as dose escalation was not possible, the study is reported as a phase II study of the combination to assess response and toxicity. A total of 51 patients with locally advanced or metastatic breast cancer were treated on this phase II study, with doses of docetaxel 50 mg m⁻², epirubicin 50 mg m⁻² and infusional 5-FU 200 mg m⁻² day⁻¹ for 21 days. The main toxicity of this combination was neutropenia with 89% of patients having grade 3 and 4 neutropenia, and 39% of patients experiencing febrile neutropenia. Nonhaematological toxicity was mild. The overall response rate in the assessable patients was 64%, with median progression-free survival of 38 weeks, and median survival of 70 weeks. The ETF regimen was found to be toxic, and it was not possible to escalate the dose of docetaxel above the first dose level. This regimen has therefore not been taken any further, but as a development of this a new study is ongoing, combining 3-weekly epirubicin, weekly docetaxel and capecitabine, days 1-14

A Hierarchical Multilevel Markov Chain Monte Carlo Algorithm with Applications to Uncertainty Quantification in Subsurface Flow

In this paper we address the problem of the prohibitively large computational cost of existing Markov chain Monte Carlo methods for large--scale applications with high dimensional parameter spaces, e.g. in uncertainty quantification in porous media flow. We propose a new multilevel Metropolis-Hastings algorithm, and give an abstract, problem dependent theorem on the cost of the new multilevel estimator based on a set of simple, verifiable assumptions. For a typical model problem in subsurface flow, we then provide a detailed analysis of these assumptions and show significant gains over the standard Metropolis-Hastings estimator. Numerical experiments confirm the analysis and demonstrate the effectiveness of the method with consistent reductions of more than an order of magnitude in the cost of the multilevel estimator over the standard Metropolis-Hastings algorithm for tolerances $\varepsilon < 10^{-2}$

Zoledronic acid significantly improves pain scores and quality of life in breast cancer patients with bone metastases: a randomised, crossover study of community vs hospital bisphosphonate administration

Patients with bone metastases from breast cancer often experience substantial skeletal complications – including debilitating bone pain – which negatively affect quality of life. Zoledronic acid (4 mg) has been demonstrated to reduce significantly the risk of skeletal complications in these patients and is administered via a short, 15-min infusion every 3 weeks, allowing the possibility for home administration. This study compared the efficacy and safety of zoledronic acid administered in the community setting vs the hospital setting in breast cancer patients with ⩾1 bone metastasis receiving hormonal therapy. After a lead-in phase of three infusions of 4 mg zoledronic acid in the hospital setting, 101 patients were randomized to receive three open-label infusions in the community or hospital setting, followed by three infusions in the opposite venue (a total of nine infusions). The Brief Pain Inventory (BPI) and the European Organisation for Research and Treatment of Cancer Quality of Life Core Questionnaire 30 (EORTC QLQ-C30) were used to assess potential benefits of zoledronic acid therapy. At study end, analysis of the BPI showed significant reductions in worst pain (P=0.008) and average pain in the last 7 days (P=0.039), and interference with general activity (P=0.012). In each case, there were significantly greater improvements in pain scores after treatment in the community setting compared with the hospital crossover setting for worst pain (P=0.021), average pain (P=0.003), and interference with general activity (P=0.001). Overall global health status showed a significant median improvement of 8.3% (P=0.013) at study end. Physical, emotional, and social functioning also showed significant overall improvement (P=0.013, 0.005, and 0.043, respectively). Furthermore, physical, role, and social functioning showed significantly greater improvements after treatment in the community setting compared with the hospital crossover setting (P=0.018, 0.001, and 0.026, respectively). There was no difference between hospital and community administration in renal or other toxicity, with zoledronic acid being well tolerated in both treatment settings. These data confirm the safety and quality-of-life benefits of zoledronic acid in breast cancer patients with bone metastases, particularly when administered in the community setting

Is age a barrier to chemotherapy? Rates of treatment in older patients with breast, colon or lung cancer in England in 2014: A national registry study

Background Survival from cancer in older patients is poorer in the UK than other countries with similar health systems and wealth possibly due to undertreatment and increased toxicities in this specific population. This population-based observational study describes factors affecting systemic anticancer treatment (SACT) use in older patients in England. Methods We identified patients aged ≥70 with stage II-III breast cancer, stage III colon cancer and stage IIIB-IV non-small cell lung cancer (NSCLC) diagnosed in 2014 from a dataset collected by the National Health Service in England. We used logistic regression to estimate factors affecting likelihood of receiving SACT and performed separate regression analyses for each disease, adjusting for age, gender, stage at diagnosis, pathological features, performance status, Charlson comorbidity index, ethnicity and socioeconomic group. We assessed 2-year overall survival (OS) using Kaplan-Meier method. Case mix adjusted treatment rates and workload volume were calculated at hospital level and presented using funnel plots, stratified by age groups (<70 and ≥70) to allow for assessment of variation between centres. Results 36892 patients were identified: 19879 with stage II-III breast cancer, 5292 with stage III colon cancer and 11721 with stage IIIB-IV NSCLC. Patients over 70 were less likely to receive SACT compared to those aged under 70: breast 11.7% vs 64.6%, p < 0.001; colon 37.4% vs 79%, p < 0.001; NSCLC 33.5% vs 60.2%, p < 0.001. 2-year OS for patients receiving SACT was similar for patients aged ≥70 and <70: breast 91.5% (95% CI: 89.3%-93.2%) vs 96.4% (95% CI: 95.9%-96.7%); colon 84.8% (95% CI: 82.6%-86.8%) vs 88.3% (95% CI: 86.7%-89.8%); NSCLC 16.7% (95% CI: 15.1%-18.4%) vs 19.8% (95%CI: 18.5%-21.1%). Patients receiving SACT had better OS than those untreated. SACT rates varied widely between hospitals after adjusting for case-mix across all ages. Conclusions Our study suggests that several factors affect the likelihood of receiving SACT but after adjusting for these, age remains determinant. Identifying hospitals with significantly lower SACT rates should prompt local review of multidisciplinary team practice