Management of elderly patients with breast cancer: updated recommendations of the International Society of Geriatric Oncology (SIOG) and European Society of Breast Cancer Specialists (EUSOMA)

As the mean age of the global population increases, breast cancer in older individuals will be increasingly encountered in clinical practice. Management decisions should not be based on age alone. Establishing recommendations for management of older individuals with breast cancer is challenging because of very limited level 1 evidence in this heterogeneous population. In 2007, the International Society of Geriatric Oncology (SIOG) created a task force to provide evidence-based recommendations for the management of breast cancer in elderly individuals. In 2010, a multidisciplinary SIOG and European Society of Breast Cancer Specialists (EUSOMA) task force gathered to expand and update the 2007 recommendations. The recommendations were expanded to include geriatric assessment, competing causes of mortality, ductal carcinoma in situ, drug safety and compliance, patient preferences, barriers to treatment, and male breast cancer. Recommendations were updated for screening, primary endocrine therapy, surgery, radiotherapy, neoadjuvant and adjuvant systemic therapy, and metastatic breast cancer.

Advertising, promotion, and the rise of a national building society movement in interwar Britain

This article examines the role of advertisement and promotion in the successful development of nationwide building societies in interwar Britain and the rapid overall growth of the building society movement. Major building societies are shown to have used extensive advertising to compensate for their initial lack of established national brands, promote home-ownership, and make savers aware of the attractive earnings and high security of building society savings. During a period when most building societies had very limited branch networks, extensive advertising increased the public profile of the major societies and thus assisted their rapid expansion via lower-cost modes such as agency networks.

Targeting myocardial remodelling to develop novel therapies for heart failure: a position paper from the Working Group on Myocardial Function of the European Society of Cardiology

The failing heart is characterized by complex tissue remodelling involving increased cardiomyocyte death, and impairment of sarcomere function, metabolic activity, endothelial and vascular function, together with increased inflammation and interstitial fibrosis. For years, therapeutic approaches for heart failure (HF) relied on vasodilators and diuretics which relieve cardiac workload and HF symptoms. The introduction in the clinic of drugs interfering with beta-adrenergic and angiotensin signalling have ameliorated survival by interfering with the intimate mechanism of cardiac compensation. Current therapy, though, still has a limited capacity to restore muscle function fully, and the development of novel therapeutic targets is still an important medical need. Recent progress in understanding the molecular basis of myocardial dysfunction in HF is paving the way for development of new treatments capable of restoring muscle function and targeting specific pathological subsets of LV dysfunction. These include potentiating cardiomyocyte contractility, increasing cardiomyocyte survival and adaptive hypertrophy, increasing oxygen and nutrition supply by sustaining vessel formation, and reducing ventricular stiffness by favourable extracellular matrix remodelling. Here, we consider drugs such as omecamtiv mecarbil, nitroxyl donors, cyclosporin A, SERCA2a (sarcoplasmic/endoplasmic Ca(2 +) ATPase 2a), neuregulin, and bromocriptine, all of which are currently in clinical trials as potential HF therapies, and discuss novel molecular targets with potential therapeutic impact that are in the pre-clinical phases of investigation. Finally, we consider conceptual changes in basic science approaches to improve their translation into successful clinical applications.

Re-examining the U.K.'s greatest tornado outbreak: forecasting the limited extent of tornadoes along a cold front

On 23 November 1981, a strong cold front swept across the U.K., producing tornadoes from the west to the east coasts. An extensive campaign to collect tornado reports by the Tornado and Storm Research Organisation (TORRO) resulted in 104 reports, the largest U.K. outbreak. The front was simulated with a convection-permitting numerical model down to 200-m horizontal grid spacing to better understand its evolution and meteorological environment. The event was typical of tornadoes in the U.K., with convective available potential energy (CAPE) less than 150 J kg-1, 0-1-km wind shear of 10-20 m s-1, and a narrow cold-frontal rainband forming precipitation cores and gaps. A line of cyclonic absolute vorticity existed along the front, with maxima as large as 0.04 s-1. Some hook-shaped misovortices bore kinematic similarity to supercells. The narrow swath along which the line was tornadic was bounded on the equatorward side by weak vorticity along the line and on the poleward side by zero CAPE, enclosing a region where the environment was otherwise favorable for tornadogenesis. To determine if the 104 tornado reports were plausible, first possible duplicate reports were eliminated, resulting in as few as 58 tornadoes to as many as 90. Second, the number of possible parent misovortices that may have spawned tornadoes is estimated from model output. The number of plausible tornado reports in the 200-m grid-spacing domain was 22 and as many as 44, whereas the model simulation was used to estimate 30 possible parent misovortices within this domain. These results suggest that 90 reports was plausible.