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

A game prototype for understanding the safety issues of a lifeboat launch

© 2018 The Author(s) Novel, advanced game techniques provide us with new possibilities to mimic a complicated training process, with the added benefit of enhanced safety. In this paper, we design and implement a 3D game with the support of virtual reality equipment which imitates the process of a lifeboat launch, involving both tractor manoeuvres and boat operations. It is a complex but vital process which can save lives at sea but also has many potential hazards. The primary objective of the game is to allow novices to better understand the sequence of the operations and manage the potential risks which may occur during the launch process. Additionally, the game has been promoted to the general public for educational purposes and to raise awareness of the safety issues involved. The key modules of the game are designed based on physical simulations to give the players enhanced plausible cognition and enjoyable interaction. We conducted two case studies for the two purposes of the games: one for training with volunteers without launching experience and the other for public awareness of the potential hazards with young children. The game is proven to be very promising for future professional training, and it serves the educational purpose of awareness of the safety issues for general public while being entertaining

Measurement of urinary collagen cross-links indicate response to therapy in patients with breast cancer and bone metastases

Objective assessment of response in bone metastases from breast cancer using radiological techniques takes up to 6 months of treatment to be certain of a response, and sclerotic metastases are not evaluable. Standard serum and urinary tumour markers may not always be utilized to predict response, as they may not be elevated, and therefore may not change on treatment. The development of the urinary pyridinoline cross-link assays which measure mature bone breakdown products have been shown to be highly sensitive and specific as a measure of bone change in osteoporosis. We have measured pyridinoline (Pyr) and deoxypyridinoline (Dpyr) cross-links sequentially in 36 breast cancer patients with bone metastases, to determine if the measurement of these analytes predicts response at an earlier stage than radiological assessment. Response was assessed by UICC criteria. Seventeen women responded to hormonal therapy, whilst 19 developed progressive disease. Both Pyr and Dpyr increased sequentially in women with progressive disease with changes becoming apparent by 8 weeks (P < 0.03). In responding women, cross-link levels did not change significantly. Pyr and Dpyr were more sensitive and specific than the standard serum tumour marker CA 15-3. Urinary cross-link measurements provide a novel objective method of assessing response to treatment in women with bone metastases. Initial elevated urinary cross-link markers identify patients who tend not to respond to changes in hormonal therap

Current directions in visual working memory research: An introduction and emerging insights

Visual working memory (VWM) is a core construct in the cognitive (neuro-)sciences, assumed to serve as a hub for information exchange and thus supporting a multitude of cognitive functions related to processing visual information. Here, we give an introduction into key terms and paradigms and an overview of ongoing debates in the field, to which the articles collected in this Special Issue on 'Current Directions in Visual Working Memory Research' contribute. Our aim is to extract, from this overview, some 'emerging' theoretical insights concerning questions such as the optimal way to examine VWM, which types of mental representations contribute to performance on VWM tasks, and how VWM keeps features from the same object together and apart from features of concurrently maintained objects (the binding problem)

Timing of singleton births by onset of labour and mode of birth in NHS maternity units in England, 2005-2014: A study of linked birth registration, birth notification, and hospital episode data

BACKGROUND: Maternity care has to be available 24 hours a day, seven days a week. It is known that obstetric intervention can influence the time of birth, but no previous analysis at a national level in England has yet investigated in detail the ways in which the day and time of birth varies by onset of labour and mode of giving birth. METHOD: We linked data from birth registration, birth notification, and Maternity Hospital Episode Statistics and analysed 5,093,615 singleton births in NHS maternity units in England from 2005 to 2014. We used descriptive statistics and negative binomial regression models with harmonic terms to establish how patterns of timing of birth vary by onset of labour, mode of giving birth and gestational age. RESULTS: The timing of birth by time of day and day of the week varies considerably by onset of labour and mode of birth. Spontaneous births after spontaneous onset are more likely to occur between midnight and 6am than at other times of day, and are also slightly more likely on weekdays than at weekends and on public holidays. Elective caesarean births are concentrated onto weekday mornings. Births after induced labours are more likely to occur at hours around midnight on Tuesdays to Saturdays and on days before a public holiday period, than on Sundays, Mondays and during or just after a public holiday. CONCLUSION: The timing of births varies by onset of labour and mode of birth and these patterns have implications for midwifery and medical staffing. Further research is needed to understand the processes behind these findings

Increasing the dose intensity of chemotherapy by more frequent administration or sequential scheduling: a patient-level meta-analysis of 37 298 women with early breast cancer in 26 randomised trials

Background Increasing the dose intensity of cytotoxic therapy by shortening the intervals between cycles, or by giving individual drugs sequentially at full dose rather than in lower-dose concurrent treatment schedules, might enhance efficacy. Methods To clarify the relative benefits and risks of dose-intense and standard-schedule chemotherapy in early breast cancer, we did an individual patient-level meta-analysis of trials comparing 2-weekly versus standard 3-weekly schedules, and of trials comparing sequential versus concurrent administration of anthracycline and taxane chemotherapy. The primary outcomes were recurrence and breast cancer mortality. Standard intention-to-treat log-rank analyses, stratified by age, nodal status, and trial, yielded dose-intense versus standard-schedule first-event rate ratios (RRs). Findings Individual patient data were provided for 26 of 33 relevant trials identified, comprising 37 298 (93%) of 40 070 women randomised. Most women were aged younger than 70 years and had node-positive disease. Total cytotoxic drug usage was broadly comparable in the two treatment arms; colony-stimulating factor was generally used in the more dose-intense arm. Combining data from all 26 trials, fewer breast cancer recurrences were seen with dose-intense than with standard-schedule chemotherapy (10-year recurrence risk 28·0% vs 31·4%; RR 0·86, 95% CI 0·82–0·89; p<0·0001). 10-year breast cancer mortality was similarly reduced (18·9% vs 21·3%; RR 0·87, 95% CI 0·83–0·92; p<0·0001), as was all-cause mortality (22·1% vs 24·8%; RR 0·87, 95% CI 0·83–0·91; p<0·0001). Death without recurrence was, if anything, lower with dose-intense than with standard-schedule chemotherapy (10-year risk 4·1% vs 4·6%; RR 0·88, 95% CI 0·78–0·99; p=0·034). Recurrence reductions were similar in the seven trials (n=10 004) that compared 2-weekly chemotherapy with the same chemotherapy given 3-weekly (10-year risk 24·0% vs 28·3%; RR 0·83, 95% CI 0·76–0·91; p<0·0001), in the six trials (n=11 028) of sequential versus concurrent anthracycline plus taxane chemotherapy (28·1% vs 31·3%; RR 0·87, 95% CI 0·80–0·94; p=0·0006), and in the six trials (n=6532) testing both shorter intervals and sequential administration (30·4% vs 35·0%; RR 0·82, 95% CI 0·74–0·90; p<0·0001). The proportional reductions in recurrence with dose-intense chemotherapy were similar and highly significant (p<0·0001) in oestrogen receptor (ER)-positive and ER-negative disease and did not differ significantly by other patient or tumour characteristics. Interpretation Increasing the dose intensity of adjuvant chemotherapy by shortening the interval between treatment cycles, or by giving individual drugs sequentially rather than giving the same drugs concurrently, moderately reduces the 10-year risk of recurrence and death from breast cancer without increasing mortality from other causes. Funding Cancer Research UK, Medical Research Council

The Anglo-Saxon migration and the formation of the early English gene pool

The history of the British Isles and Ireland is characterized by multiple periods of major cultural change, including the influential transformation after the end of Roman rule, which precipitated shifts in language, settlement patterns and material culture1. The extent to which migration from continental Europe mediated these transitions is a matter of long-standing debate2–4. Here we study genome-wide ancient DNA from 460 medieval northwestern Europeans—including 278 individuals from England—alongside archaeological data, to infer contemporary population dynamics. We identify a substantial increase of continental northern European ancestry in early medieval England, which is closely related to the early medieval and present-day inhabitants of Germany and Denmark, implying large-scale substantial migration across the North Sea into Britain during the Early Middle Ages. As a result, the individuals who we analysed from eastern England derived up to 76% of their ancestry from the continental North Sea zone, albeit with substantial regional variation and heterogeneity within sites. We show that women with immigrant ancestry were more often furnished with grave goods than women with local ancestry, whereas men with weapons were as likely not to be of immigrant ancestry. A comparison with present- day Britain indicates that subsequent demographic events reduced the fraction of continental northern European ancestry while introducing further ancestry components into the English gene pool, including substantial southwestern European ancestry most closely related to that seen in Iron Age Franc