The prognostic impact of clinical and molecular features in hairy cell leukaemia variant and splenic marginal zone lymphoma.

Hairy cell leukaemia variant (HCL-variant) and splenic marginal zone lymphoma (SMZL) are disorders with overlapping features. We investigated the prognostic impact in these disorders of clinical and molecular features including IGH VDJ rearrangements, IGHV gene usage and TP 53 mutations. Clinical and laboratory data were collected before therapy from 35 HCL-variant and 68 SMZL cases. End-points were the need for treatment and overall survival. 97% of HCL-variant and 77% of SMZL cases required treatment (P = 0·009). Survival at 5 years was significantly worse in HCL-variant [57% (95% confidence interval 38-73%)] compared with SMZL [84% (71-91%); Hazard Ratio 2·25 (1·20-4·25), P = 0·01]. In HCL-variant, adverse prognostic factors for survival were older age (P = 0·04), anaemia (P = 0·01) and TP 53 mutations (P = 0·02). In SMZL, splenomegaly, anaemia and IGHV genes with >98% homology to the germline predicted the need for treatment; older age, anaemia and IGHV unmutated genes (100% homology) predicted shorter survival. IGHV gene usage had no impact on clinical outcome in either disease. The combination of unfavourable factors allowed patients to be stratified into risk groups with significant differences in survival. Although HCL-variant and SMZL share some features, they have different outcomes, influenced by clinical and biological factors.

Breaking patterns of conflict in Northern Ireland: new perspectives

Central to reaching peace and settlement in Northern Ireland was a sequence of British–Irish intergovernmental discussions and negotiations, dating from the beginning of the 1980s. British and Irish state cooperation and intervention has remained central to the stability of the settlement reached in 1998. The motives of state actors, however, have been unclear, and the role of the state in the political process has been the subject of some scholarly controversy. This paper looks at the types of evidence that can help to resolve such questions. It focuses on the value of elite interviews, arguing that they can constitute an important and irreplaceable body of evidence when used critically, but it also highlights the risks of excessive reliance on this type of source. It goes on to describe a major research project in University College Dublin whose aim was to record the experiences and interpretations of the actors who engaged in British–Irish negotiations over the last four decades. It discusses the resulting elite interviews and witness seminars and the methodological and ethical difficulties encountered. It describes how these were overcome, and outlines the conditions of confidentiality imposed.