Purpose of review Despite the availability of multiple targeted therapies, the 5-year survival rate of patients with metastatic clear cell renal cell carcinoma (ccRCC) rarely exceeds 10%. Recent insights into the mutational landscape and evolutionary dynamics of ccRCC have offered up a plausible explanation for these outcomes. The purpose of this review is to link the research findings to potential changes in clinical practice. Recent findings Intratumour heterogeneity (ITH) dominates the evolutionary landscape in ccRCC at the genetic, transcriptomic and proteomic level. Spatial and temporal separation of tumour subclones within the primary tumour as well as between primary and metastatic sites has been demonstrated at single nucleotide resolution. In the cases analysed to date, approximately two-thirds of somatic mutations are not shared between multiple biopsies from the same primary tumour. Very few of the key disease-driving events are shared across all primary tumour regions (with the exception of VHL and loss of chromosome 3p), whereas the majority are restricted to one or more tumour regions (TP53, SETD2, BAP1, PTEN, mTOR, PIK3CA and KDM5C). Summary ITH must be considered in the management of ccRCC with respect to diagnostic procedures, prognostic and predictive biomarkers and drug development.

THE CONTENT OF THE BOOK: The book has 290 pages, and the content is divided into 10 chapters. In the introductory chapters written something about the origin of cocoa beans, its basic characteristics, and the impact on human health. In subsequent following chapters describes the technological process of production of chocolate harvesting, fermentation and drying of cocoa beans, through its preparations in terms in the sense of burning and shredding, the production of cocoa powder and chocolate mass from it, and chocolate and chocolate products. In the book are described rheological properties as a very important factor in the quality of chocolate products, and finally an overview of some types of chocolate, as well as the basic quality properties of chocolate. The book has a large number of pictures, diagrams and tables which are complemented content of book. The book will be published on the website and will be accessible to anyone who is interested in its subject matter.

Objective: to analyze factors associated with births not registered at a National Health System (SUS) maternity hospital registry office in Nova Iguacu-RJ, Brazil. Methods: a cross-sectional study of data on 468 live births (LB) between June-July 2012. The dependent variable was births not registered at the registry office within 15 days following birth. Prevalence ratios (PR) and 95% confidence intervals (95% CI) were estimated using Poisson Regression. Results: 40.6% (190/468) of LB were not registered at the registry office. Non-registration was positively associated with little or no maternal schooling (PR 1.41; 95% CI 1.04-1.93), childbirth prior to hospitalization (PR 2.15; 95% CI 1.04-4.46), and mother resident in a different municipality to the hospital (PR 1.39; 95%% CI 1.03-1.89). Conclusion: mothers with little or no schooling and who do not give birth in hospital should receive guidance on birth registration.

ABSTRACT Developments in information technology are providing methods to improve current design practices, where uncertainties about various design elements can be simulated and studied from the de...