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.

Preterm delivery before 37 gestational weeks is a major challenge in perinatal health care. Over the past 30, the incidence of preterm delivery in most developed countries has been about 7–10% of live births. Some evidence shows that this incidence has increased slightly in the past few years, but the rate of birth before 32 weeks' gestation is almost unchanged, at 1-2%. Several factors have contributed to the overall rise in the incidence of preterm delivery. These factors include increased use of assisted reproduction techniques, increasing rates of multiple births, and more obstetric intervention. Progesterone is the key hormone maintaining pregnancy. Numerous progesterone effects can be demonstrated by laboratory studies involving every tissue of the reproductive tract, the myometrium, decidua, cervix, and fetal membranes. In particular, progesterone can alter the response to cytokines, inhibit prostaglandin and nitric oxide synthesis, reduce corticotrophin-releasing hormone (CRH) synthesis, block cervical stromal degradation, and induce cervical stromal matrix protein secretion. By altering both the mechanical and physiologic functions of the cervix, cervical performance may be substantially enhanced by these agents. Presumably, progesterone may alter the rate of cervical stromal degradation via altering secretion of matrix metalloproteases by diminishing prostaglandin and nitric oxide synthesis and minimizing neutrophil recruitment. The diverse aetiology of preterm delivery makes its prediction difficult. A substantial part of unexplained preterm deliveries might be attributable to a deleterious immune response of the mother toward the foetus. A growing body of evidence suggests that progesterone might play a significant role in establishing an adequate immune environment during the early stages of pregnancy. In the presence of progesterone, lymphocytes of pregnant women release a protein named the progesterone induced blocking factor (PIBF)7 which mediates the immunomodulatory and antiabortive effects of progesterone. Immunologic recognition of pregnancy and subsequent activation of maternal immune system result in an upregulation of progesterone receptors on activated lymphocytes among placental cells and CD8+ cells. In the presence of sufficient progesterone levels, these cells synthesize PIBF. Patients at risk of preterm delivery presented increased proinflammatory cytokines, low PIBF, and reduced IL-10 expressions on lymphocytes. PIBF alters the profile of cytokine secretion of activated lymphocytes shifting the balance toward Th2 dominance. During a normal uneventful pregnancy, the concentration of PIBF continuously increases from the 7th to the 37th gestational weeks. After the 41st week of pregnancy, PIBF concentrations dramatically decrease. In patients with a diagnosis of threatened premature labour, studies have shown that PIBF levels failed to increase during pregnancy. Identification of women with risk for preterm delivery would be a key for its prevention. No sufficiently specific marker, however, has so far been found. The diverse aetiology of preterm birth makes its prediction difficult. This special issue will give as some useful information but also questions which are important for our understanding of pathophysiology, prevention, diagnosis, and treatment of preterm birth. Igor  Hudic Babill  Stray-Pedersen Vajdana  Tomic

This study, developed from research carried out during a master’s program, focuses on the historical, normative and political trajectory of agricultural education (at high school level), now in the context of federal legislation reforms. This segment of vocational education developed in the light of stereotypes and isolation, with scarce scientific analysis as rare object of research. This paper aims to present a descriptive and analytical approach to the main normative acts that guided the historical and curricular trajectory of Agricultural Education at high school level. Highlighting the educational policies embodied in the federal educational legislation, within these major historical milestones: from Imperial Brazil to the Republican period (1960). Based on qualitative research on education, with emphasis on documentary / normative and institutional research, it is necessary to identify the multiple historical determinations that outlined and preceded current secondary vocational education policies (agricultural area) aiming to offer contributions for the analysis of contemporary policies.

This study deals with estimation of the surface free energy of thin films of polyaniline doped with phosphoric acid, by measuring contact angles. Synthesis of polyaniline (PANI) with phosphoric acid (PA) was performed at room temperature of 20°C, and at 0°C. Thin films were obtained by means of a spin coater, applying the synthetized mixture on a glass substrate. By measuring the contact angle, first between ethylene glycol and a film and then between distilled water and a film, we thus calculated the polar, dispersion and total surface free energy. It was proved and demonstrated that the surface free energy depends on the temperature at which the solution (from which the thin films are obtained later) was synthesized.

Objectives To compare the efficacy, safety, immunogenicity and pharmacokinetics (PK) of SB2 to the infliximab reference product (INF) in patients with moderate to severe rheumatoid arthritis (RA) despite methotrexate therapy. Methods This is a phase III, randomised, double-blind, multinational, multicentre parallel group study. Patients with moderate to severe RA despite methotrexate therapy were randomised in a 1:1 ratio to receive either SB2 or INF of 3 mg/kg. The primary end point was the American College of Rheumatology 20% (ACR20) response at week 30. Inclusion of the 95% CI of the ACR20 response difference within a ±15% margin was required for equivalence. Results 584 subjects were randomised into SB2 (N=291; 290 analysed) or INF (N=293). The ACR20 response at week 30 in the per-protocol set was 64.1% in SB2 versus 66.0% in INF. The adjusted rate difference was −1.88% (95% CI −10.26% to 6.51%), which was within the predefined equivalence margin. Other efficacy outcomes such as ACR50/70, disease activity score measured by 28 joints and European League against Rheumatism response were similar between SB2 and INF. The incidence of treatment-emergent adverse events was comparable (57.6% in SB2 vs 58.0% in INF) as well as the incidence of antidrug antibodies (ADA) to infliximab up to week 30 (55.1% in SB2 vs 49.7% in INF). The PK profile was similar between SB2 and INF. Efficacy, safety and PK by ADA subgroup were comparable between SB2 and INF. Conclusions SB2 was equivalent to INF in terms of ACR20 response at week 30. SB2 was well tolerated with a comparable safety profile, immunogenicity and PK to INF. Trial registration number NCT01936181.

Through the bibliometric and co-citation analysis, this paper offers a review of science achievements in the area of e-learning continuance, with focus on identification of the field relevance, authors and most cited and co-cited papers, as well as the identification of roots this research area is based on. Based on co-citation network, which chronologically starts with Ajzen’s theory of 1975, another contribution can be drawn from this paper. That contribution leads to a conclusion that Ajzen’s Theory of planned behavior is a starting and adequate basis for all identified research and creates a main recommendation for upcoming researches.

Research activities in the field of modern Biomedical engineering show a more intense trend towards the use of sophisticated engineering measurement tools in order to optimize existing medical devices. External fixators are such an example of the above mentioned. Critical design parameters are being optimized by the use of existing engineering research methodology. One of the most important parameter for external fixators that have to be tracked are the interfragmentary displacements between the proximal and distal bone segment. This is usually achieved by the use of a finite element method. Another way is the use of displacement sensors or transducers. To verify these numerical results and to gain additional real life footage of interfragmentary displacements during testing, the use of a high speed camera has been taken into consideration. This paper compares previously acquired numerical data for a specific external fixator design parallel to the same setup whilst being recorded with a high speed camera. Results indicate good superposition with previously obtained data.