A feasibility study testing four hypotheses with phase II outcomes in advanced colorectal cancer (MRC FOCUS3): a model for randomised controlled trials in the era of personalised medicine?

Background: Molecular characteristics of cancer vary between individuals. In future, most trials will require assessment of biomarkers to allocate patients into enriched populations in which targeted therapies are more likely to be effective. The MRC FOCUS3 trial is a feasibility study to assess key elements in the planning of such studies.

Patients and methods: Patients with advanced colorectal cancer were registered from 24 centres between February 2010 and April 2011. With their consent, patients' tumour samples were analysed for KRAS/BRAF oncogene mutation status and topoisomerase 1 (topo-1) immunohistochemistry. Patients were then classified into one of four molecular strata; within each strata patients were randomised to one of two hypothesis-driven experimental therapies or a common control arm (FOLFIRI chemotherapy). A 4-stage suite of patient information sheets (PISs) was developed to avoid patient overload.

Results: A total of 332 patients were registered, 244 randomised. Among randomised patients, biomarker results were provided within 10 working days (w.d.) in 71%, 15 w.d. in 91% and 20 w.d. in 99%. DNA mutation analysis was 100% concordant between two laboratories. Over 90% of participants reported excellent understanding of all aspects of the trial. In this randomised phase II setting, omission of irinotecan in the low topo-1 group was associated with increased response rate and addition of cetuximab in the KRAS, BRAF wild-type cohort was associated with longer progression-free survival.

Conclusions: Patient samples can be collected and analysed within workable time frames and with reproducible mutation results. Complex multi-arm designs are acceptable to patients with good PIS. Randomisation within each cohort provides outcome data that can inform clinical practice.

Land, Popular Politics and Agrarian Violence in Late Nineteenth Century Ireland

"Land, Popular Politics and Agrarian Violence in Ireland" provides an original and insightful study of the highly formative Land War and Home Rule from a local and regional perspective. Lucey examines the emergence and development of the largest mass political mobilisation brought about in nineteenth-century Ireland in the form of the Land League, and subsequently the National League, in the south-western county of Kerry. Such an unprecedented level of local political activity was matched by an upsurge in agrarian violence and the outbreak of serious outrage, which was largely orchestrated by secret societies known as Moonlighters. In turn, this book provides an important exploration of the dynamics behind the mass political mobilisation and agrarian violence that dominated Kerry society during the 1880s. The role of Fenians, radical agrarian agitators and moderate constitutional nationalists are all examined within the county.This study has importance beyond the local and provides a range of insights into motivations behind political action and violence at an everyday level during one of the most seminal and transformative eras in the development of modern Irish history. This title is suitable for students and academics of nineteenth-century Irish history and general readers.

Expert opinion on the cough hypersensitivity syndrome in respiratory medicine

In 2011, a European Respiratory Society Task Force embarked on a process to determine the position and clinical relevance of the cough hypersensitivity syndrome, a disorder characterised by troublesome coughing often triggered by low levels of thermal, mechanical or chemical exposure, in the management of patients with chronic cough. A 21-component questionnaire was developed by an iterative process supported by a literature review. 44 key opinion leaders in respiratory medicine were selected and interviewed as to their opinions. There was a high degree of unanimity in the responses obtained, with all opinion leaders supporting the concept of cough hypersensitivity as a clinically useful paradigm. The classic stratification of cough into asthmatic, rhinitic and reflux-related phenotypes was supported. Significant disparity of opinion was seen in the response to two questions concerning the therapy of chronic cough. First, the role of acid suppression in reflux cough was questioned. Secondly, the opinion leaders were split as to whether a trial of oral steroids was indicated to establish a diagnosis of eosinophilic cough. The cough hypersensitivity syndrome was clearly endorsed by the opinion leaders as a valid and useful concept. They considered that support of patients with chronic cough was inadequate and the Task Force recommends that further work is urgently required in this neglected area.

The Pinnacle of Popular Taste?: The Importance of Confessions of a Window Cleaner (1974)

Loathed by critics, the British sexploitation comedy Confessions of a Window Cleaner (1974) was dismissed as tawdry and vulgar yet its massive popular appeal makes it an important indicator of popular taste in the much-maligned 1970s. Using new archival material, this article examines what the film offered and how it was deliberately crafted in order to appeal to a variety of audiences.

Revolting Arts or Spatial Democracy: Performances of popular arts during the Egyptian Revolution?

This paper investigates how spatial practices of Public art performance had transformed public space from being a congested traffic hub into an active and animated space for resistance that was equally accessible to different factions, social strata, media outlets and urban society, determined by popular culture and social responsibility. Tahrir Square was reproduced, in a process of “space adaptation” using Henri Lefebvre’s term, to accommodate forms of social organization and administration.205 Among the spatial patterns of activities detected and analyzed this paper focus on particular forms of mass practices of art and freedom of expression that succeeded to transform Tahrir square into performative space and commemorate its spatial events. It attempts to interrogate how the power of artistic interventions has recalled socio-cultural memory through spatial forms that have negotiated middle grounds between deeply segregated political and social groups in moments of utopian democracy. Through analytical surveys and decoding of media recordings of the events, direct interviews with involved actors and witnesses, this paper offers insight into the ways protesters lent their artistry capacity to the performance of resistance to become an act of spatial festivity or commemoration of events. The paper presents series of analytical maps tracing how the role of art has shifted significantly from traditional freedom of expression modes as narrative of resistance into more sophisticated spatial performative ones that take on a new spatial vibrancy and purpose.

The Cultures of Popular Culture

Special Issue of the 'Proceedings of the Royal Irish Academy Modern Languages Symposium', reflecting a selection of papers from the Belfast Conference (13th-14th December 2013)