Prognostic relevance of number and bilaterality of positive surgical margins after radical prostatectomy

Item does not contain fulltextPURPOSE: Positive surgical margin (PSM) status following radical prostatectomy (RP) is a well-established prognostic factor. The aim of the present study is to evaluate whether number of PSMs or bilaterality of PSMs might have prognostic significance for biochemical recurrence (BCR) in the population with a PSM status following RP. METHODS: We evaluated 1,395 RP pathology reports from our center between 1980 and 2006. All patients who underwent (neo)-adjuvant therapy were excluded, leaving a cohort of 1,009 patients, with 249 (24.7%) subjects having a PSM at RP of whom 29.4% had multiple PSMs (>/= 2 sites), while 13.6% had bilateral PSMs. Median follow-up was 40 months (range 0-258 months). We used BCR-free survival as the primary study outcome. BCR was defined as any rise in PSA above or equal to 0.2 ng/ml. RESULTS: Of patients with a PSM status, 41% (95% CI: 33-49%) developed BCR within 5 years, compared to 12% (95% CI: 9-15%) in the population without a PSM. Multivariable analysis identified PSA at diagnosis and RP Gleason score as independent predictive factors for BCR. Increasing number and/or bilaterality of PSM did not lead to significant higher rates of BCR. CONCLUSION: In patients with a PSM, the number of positive sites or bilaterality of PSM status does not add prognostic information for risk of BCR. Survival curve slopes were different for patients with bilateral PSM, showing a significant tendency to progress to BCR earlier during follow-up than patients with unilateral PSM.1 februari 201

Endogenous laminin is required for human airway smooth muscle cell maturation

BACKGROUND: Airway smooth muscle (ASM) contraction underlies acute bronchospasm in asthma. ASM cells can switch between a synthetic-proliferative phenotype and a contractile phenotype. While the effects of extracellular matrix (ECM) components on modulation of ASM cells to a synthetic phenotype have been reported, the role of ECM components on maturation of ASM cells to a contractile phenotype in adult lung is unclear. As both changes in ECM components and accumulation of contractile ASM are features of airway wall remodelling in asthma, we examined the role of the ECM protein, laminin, in the maturation of contractile phenotype in human ASM cells. METHODS: Human ASM cells were made senescence-resistant by stable expression of human telomerase reverse transcriptase. Maturation to a contractile phenotype was induced by 7-day serum deprivation, as assessed by immunoblotting for desmin and calponin. The role of laminin on ASM maturation was investigated by comparing the effects of exogenous laminin coated on culture plates, and of soluble laminin peptide competitors. Endogenous expression of laminin chains during ASM maturation was also measured. RESULTS: Myocyte binding to endogenously expressed laminin was required for ASM phenotype maturation, as laminin competing peptides (YIGSR or GRGDSP) significantly reduced desmin and calponin protein accumulation that otherwise occurs with prolonged serum deprivation. Coating of plastic cell culture dishes with different purified laminin preparations was not sufficient to further promote accumulation of desmin or calponin during 7-day serum deprivation. Expression of α2, β1 and γ1 laminin chains by ASM cells was specifically up-regulated during myocyte maturation, suggesting a key role for laminin-2 in the development of the contractile phenotype. CONCLUSION: While earlier reports suggest exogenously applied laminin slows the spontaneous modulation of ASM to a synthetic phenotype, we show for the first time that endogenously expressed laminin is required for ASM maturation to the contractile phenotype. As endogenously expressed laminin chains α2, β1 and γ1 are uniquely increased during myocyte maturation, these laminin chains may be key in this process. Thus, human ASM maturation appears to involve regulated endogenous expression of a select set of laminin chains that are essential for accumulation of contractile phenotype myocytes

The New Economy and New Business Models

This chapter tackles the definition of New Economy, its main elements and its transformation, a theoretical perspective, the economics of digital information; negligible marginal costs, network externalities and barriers and enablers of business model change. Digital Business Models; origins, concept, guidelines to develop a consensus for the business models and Digital Business Models best practices identified are also outlined. The chapter draws to a close with the key information regarding the main characteristics for E-Business Environment: generic e-Business Strategies, new Strategies for E-Organizations and new Digital Business Models for E-Organizations.2019-2

Youth Identity, Peace and Conflict: Insights from Conflict and Diverse Settings

Many of today’s youth are growing up and developing their sense of self in settings where identities are contested. Such identity dynamics play a key role in societal functioning, with group conflict often arising and being maintained due to competing social identities. Understanding how youth develop these social identities, and the consequences for peaceful and violent behaviours is of urgent importance in order to design appropriate policies and interventions. Much of the social psychological research on identity is based on social identity theory, which posits that we divide our world into social categories and define ourselves in terms of group belonging. The expressions of these social identities can be both positive and negative in how they are manifested in conflict and diverse settings. Whilst research often focuses on the negative side of identification (e.g., prejudice), identities can also be a source of peace; fostering individual belonging in society and under certain conditions, collective identities can also bring together groups in conflict. In this chapter, we briefly review the development of adolescent ethnic identity and then focus on the impact of identity for youth in conflict and diverse settings, highlighting positive and negative effects. This includes a consideration of the consequences of identity for peaceful and non-peaceful behaviours in Northern Ireland as well as how identity develops for ethnic minority youth in England. We conclude by providing suggestions for policy, practice and future research, arguing that a comprehensive account of the role of youth in society cannot be complete without understanding the development and consequences of identity processes.Richard Benjamin TrustBritish Academy/Leverhulm

A Critical Reflection on Smart Governance in Italy: Definition and Challenges for a Sustainable Urban Regeneration

The aim of this work is to analyze the projects carried out by public institutions in the field of smartness, in order to reflect on the most effective mechanisms of governance. To this end, the paper is organized into two main sections. The first section provides a literature analysis of theoretical frameworks as they pertain to the role of political bodies, the policies, and their impacts on local communities in relation to the governance of smart cities. The second section explores the ongoing implementation of "smart city" projects in Italy, in order to understand how cities address their development perspectives from a conceptual framework to the construction of an actual urban space, faced with divergent politics, messy social systems, and different scales of urban governance. In this framework, disparities between urban governance scales and ideologies encompassing smart cities seem linked to the relational systems that local administrations can develop between neighboring cities. The final section summarizes the authors' conclusions, giving particular attention to how networked urban systems are programmed, because they have been found to be key to strategic and transformative planning