Dose-response relationship in phase 1 clinical trials: a European Drug Development Network (EDDN) Collaboration Study

Introduction: Because a dose–response relationship is characteristic of conventional chemotherapy, this concept is widely used for the development of novel cytotoxic (CTX) drugs. However, the need to reach the MTD to obtain optimal benefit with molecularly targeted agents (MTA) is controversial. In this study, we evaluated the relationship between dose and efficacy in a large cohort of phase I patients with solid tumors.

Experimental Design: We collected data on 1,182 consecutive patients treated in phase I trials in 14 European institutions in 2005–2007. Inclusion criteria were: (i) patients treated within completed single-agent studies in which a maximum-administered dose was defined and (ii) RECIST/survival data available.

Results: Seventy-two percent of patients were included in trials with MTA (N = 854) and 28% in trials with CTX (N = 328). The objective response (OR) rate was 3% and disease control at 6 months was 11%. OR for CTX was associated with higher doses (median 92% of MTD); this was not the case for MTA, where patients achieving OR received a median of 50% of MTD. For trials with MTA, patients treated at intermediate doses (40%–80%) had better survival compared with those receiving low or high doses (P = 0.038). On the contrary, there was a direct association between higher dose and better OS for CTX agents (P = 0.003).

Conclusion: Although these results support the development of novel CTX based on MTD, we found no direct relationship between higher doses and response with MTA in unselected patients. However, the longest OS was seen in patients treated with MTA at intermediate doses (40%–80% of MTD)

European urban spaces in crisis - the mapping of affective pracitices with Living with Difference: introduction

The introduction outlines the notion of urban space and crisis in Europe while taking into account the more recent protests and riots in different cities, in and beyond Europe. It is argued that the phenomen of protest is happening alongside the economic crisis underscoring an alternative political public civic spirit expressing to a certain degree the renaissance and timely making of, what might be called in the digital age, #œuvre. Its forces and emotional properties capture a political realm that unfolds as a globalized urban transnational public space, still progressing. Further, it introduces the collection of papers for the special themed feature. Five papers look at affective practices through a Continental European lens, which places the meaning of race, migration and intersecting identity angles at the centre of debates of individual encounters in public spaces. The final and sixth paper, written by Brenda Yeoh, looks through a Singapore/East Asia lens, and comments on the common European threats as well as on the historical specificity and implications of distinctive geo-political spaces for affective practices.

Seeking the New Normal? Troubled Spaces of Encountering Visible Differences in Warsaw

In times of globalisation and super-mobility, ideas of normality are in turmoil. In different societies in, across and beyond Europe, we face the challenge of undoing specific notions of normality and creating more inclusive societies with an open culture of learning to live with differences. The scope of
the paper is to introduce some findings on encounters with difference and negotiations of social values in relation to a growing visibility of difference after 1989 in Poland, on the background of a critique of normality/normalisation and normalcy.On the basis of interviews conducted inWarsaw, we investigate how normality/normalisation discourses of visible homosexuality and physical disability are incorporated into individual self-reflections and justifications of prejudices (homophobia and disabilism). More specifically we argue that there are moments of ‘cultural transgressions’ present in everyday practices towards ‘visible’sexual and (dis)ability difference.

Temporary Places > Community Garden > Peaspark

Temporary Places is a community and art project in North Belfast at two interface areas, New Lodge and Skegoneill/ Glandore. This project (Jan 2013-ongoing) is a collaboration between New Lodge Arts
(lead administrative partner), PS2 (project curators) and Skegoneill & Glandore Common Purpose (community organisation). ‘Temporary Places’ was and still is a project about social and urban regeneration, partly through familiar strategies and activities and partly through more unorthodox, direct and creative interventions. It is an art and community project for all residents and the wider community.

There are several components to the project, but the key and ongoing element is to activate the empty spaces at the Skegoniell / Glandore Interface, by making a 'garden space' of creative activity - now known as Peaspark