GM-CSF receptor targeted treatment of primary AML in SCID mice using Diphtheria toxin fused to huGM-CSF

The severe combined immunodeficient (SCID) mouse model may be used to evaluate new approaches for the treatment of acute myeloid leukemia (AML). We have previously demonstrated the killing of SCID mouse leukemia initiating cells by in vitro incubation with human GM-CSF fused to Diphtheria toxin (DT-huGM-CSF). In this report, we show that in vivo treatment with DT-huGM-CSF eliminates AML growth in SCID mice. Seven cases of AML were studied. SCID mice were treated intraperitoneally with the maximally tolerated dose of 75 microg/kg/day for 7 days. Antileukemic efficacy was determined at days 40 and 80 after transplantation, by enumerating the percentages of human cells in SCID bone marrow using flow cytometry and short tandem repeat polymerase chain reaction (STR-PCR) analysis. Four out of seven AML cases were sensitive to in vivo treatment with DT-huGM-CSF at both evaluation time points. In three of these cases, elimination of human cells was demonstrated by flow cytometry and STR-PCR. One AML case showed moderate sensitivity for DT-huGM-CSF, and growth of the two remaining AML cases was not influenced by DT-huGM-CSF. Sensitivity was correlated with GM-CSFR expression. Our data show that DT-huGM-CSF can be used in vivo to reduce growth of AML and warrant further development of DT-huGM-CSF for the treatment of human AML.

Who Knows What's Going On? Mapping New Security Landscapes in Contemporary Espionage Fiction

This article explores whether or to what extent the contemporary espionage novel is able to map and interrogate transformations in the post-9/11security environment. It asks how well a form or genre of writing, typically handcuffed to the machinations and demands of the Cold War and state sovereignty, is able to adapt to a new security environment characterized by strategies of “risk assessment” and “resilience-building” and by modes or regimes of power not reducible to, or wholly controlled by, the state. In doing so, it thinks about the capacities of this type of fiction for “resisting” the formations of power it wants to make visible and is partly complicit with.

Contribution of biobanks to care services

Approaches to the management of patients with cancer have been revolutionised by the ability to examine tumours at a genetic and molecular level and tailor treatments accordingly. Underpinning this work is the need for large numbers of high-quality human biospecimens for use in translational research studies to identify new biomarkers for the prediction, diagnosis and treatment of cancer. Biobanking has subsequently emerged as a dedicated activity to provide the infrastructure required for the standardised collection, storage and distribution of high quality human biospecimens for research purposes. This article provides an overview of the role of biobanks and the vital contribution they make to the delivery of cancer care for patients now and in the future

Clustering-Based Ensemble Method as an Alternative to Stacking

One of the most popular techniques of generating classifier ensembles is known as stacking which is based on a meta-learning approach. In this paper, we introduce an alternative method to stacking which is based on cluster analysis. Similar to stacking, instances from a validation set are initially classified by all base classifiers. The output of each classifier is subsequently considered as a new attribute of the instance. Following this, a validation set is divided into clusters according to the new attributes and a small subset of the original attributes of the instances. For each cluster, we find its centroid and calculate its class label. The collection of centroids is considered as a meta-classifier. Experimental results show that the new method outperformed all benchmark methods, namely Majority Voting, Stacking J48, Stacking LR, AdaBoost J48, and Random Forest, in 12 out of 22 data sets. The proposed method has two advantageous properties: it is very robust to relatively small training sets and it can be applied in semi-supervised learning problems. We provide a theoretical investigation regarding the proposed method. This demonstrates that for the method to be successful, the base classifiers applied in the ensemble should have greater than 50% accuracy levels.

From 'trailing wives' to the emergence of a 'trailing husbands' phenomenon: Retirement migration to rural areas

Migration and gender studies have focused on economically active heterogeneous couples and traditionally highlight a dominant male role in migration decision-making. The female partner is commonly portrayed as a 'trailing wife' or 'trailing mother' with the move found to have a negative effect on her employment prospects. Much less is known about if or how the balance of power shifts between husbands and wives when employment or career-motivated moves are removed from the decision-making process. This is analysed with reference to retirement migration to rural areas of the UK and involved interviews with both partners present. For this cohort of retired couples, and in common with the literature, migration during economically active life course stages demonstrates strong 'trailing wife' and 'trailing mother' tendencies. The male's decision to retire signalled the commencement of a retirement life course stage for the couple. However, in contrast to the earlier male dominated decision-making, retirement migration saw the emergence of a 'trailing husband' phenomenon. Wives appear to adapt most successfully to the new rural environment while many husbands found it difficult to adjust (at least initially) to the multiple life changes: moving from largely urban areas to a rural setting alongside exiting the workforce. The findings suggest that the role of leader/ follower changed during the course of these couples' lives together and in relation to their reasons for moving.

The Promise of Peace:Revisiting the Northern Irish Model

The Northern Ireland peace process is often eulogized as a successful model of conflict transformation. Although the process exhibited many of the problems that beset other societies seeking to move from conflict to a negotiated peace (including disagreements over the functioning of institutions and the meanings of cultural symbols, unresolved issues relating to the effects of political violence on victims and survivors and society at large; and the residual presence of violent and political ‘spoiler’ groups), the resilience of political dialogue has proven remarkable.
This collection revisits the promise of ‘a truly historic opportunity for a new beginning’ a decade and a half on from the signing of the Belfast/Good Friday Agreement in 1998. The book will bring together academics from across a number of disciplines, including management and organizational behaviour, law, politics, sociology, archaeology and literature.

The different contributions aim to assess what impact it has made in the legal, policy, and institutional areas it specifically targeted: political reform, human rights and equality provision, working through legacies of the past (including police reform, prisoner release and victims' rights) and the building of new relationships within the island of Ireland and between Ireland and Britain. With the emergence of first-time voters who had no direct experience of the violence the book explores what the Agreement offers for future generations.

The book is the culmination of a 12-month research project sponsored by the British Academy and Leverhulme that addressed the following aspects of the peace process:
Peace walls: The euphemistically named peace walls remain one of the most visible reminders of Northern Ireland’s divisions and they are famously the only material manifestations of the conflict that have grown in number and extent since the 1998 Agreement. They were originally placed between antagonistic neighbouring communities – often at their request – at times of heightened tensions. Research under this theme explored the lack of ongoing engagement with their continuing presences, evolving meanings and impact on the communities that reside beside them needs to be overtly addressed.
Cultural division: Cultural differences have often been seen as lying at the heart of the ‘Irish problem’. Despite this, art and artists have increasingly been seen as having the potential to develop new discourses. Research explored the following questions: What role can the arts play in re-imagining the spaces opened up by the promises of the 1998 Agreement? What implication does the confrontation with the legacies of conflict have for artistic practices? What impact do the arts have on constructions of identity, on narratives of history, and on electoral politics?
Institutional transformation: This strand of research explored the significance of the process of organizational change which followed the establishment of the 1998 on political and other public policy institutions such as the police and prison services. It suggested that the experience and lessons learned from such periods of transition have much to contribute to how Northern Ireland begins to address political polarization in other areas of public service infrastructure, chiefly around the sectarian monoliths of education and housing.
Working through the past: ‘Legacy’ issues have gained increasing prominence since 1998: issues to do with public symbolism (particularly relating to the flying of flags and parading), defining victimhood, securing victims’ rights, recovery of the ‘disappeared’, reintegrating ex- prisoners back into society, and the possibilities for truth recovery and reconciliation have all acquired salient and emotive force. Although the 1998 Agreement promised to ‘honour the dead’ through a ‘new beginning’, it is increasingly unclear as to whether an agreed narrative about the past is possible – or even worthwhile pursuing. Research under this theme looked at the complex relationship between memory, commemoration and violence; how commemorative events are performed, organized, policed and represented. It also addressed the fraught issue of how to come to terms with Northern Ireland’s divided and bloodied past.

The editors are in the process of guiding contributors to adapt their papers, which were presented to a series of workshops on the above themes, to the purposes of the book. In particular, the contributors will be guided to focus on the related aims of assessing the extent of change that has occurred and providing an assessment of what remains to be done. To that end, contributors are asked to engage directly with the questions that close the ‘Introduction’, namely: To what extent has the ‘promise’ of the 1998 Agreement been fulfilled? To what extent has the 1998 Agreement given rise to forms of exclusion? To what extent has the 1998 Agreement shaped new forms of debate, dispute and engagement? In the absence of that guidance having been sent out yet, the outlines below are, for the time being, the abstracts of their original papers.