Follicular lymphoma (FL) is typically an indolent disease, but 30-40% of FL cases transform into an aggressive lymphoma (tFL) with a poor prognosis. To identify the genetic changes that drive this transformation, we sequenced the exomes of 12 cases with paired FL and tFL biopsies, and identified 45 recurrently mutated genes in the FL-tFL dataset and 39 in the tFL cases. We selected 496 genes of potential importance in transformation and sequenced them in 23 additional tFL cases. Integration of the mutation data with copy-number abnormality (CNA) data provided complementary information. We found recurrent mutations of miR-142, which has not been previously been reported to be mutated in FL/tFL. The genes most frequently mutated in tFL included KMT2D (MLL2), CREBBP, EZH2, BCL2, and MEF2B. Many recurrently mutated genes are involved in epigenetic regulation, the JAK-STAT or the NF-κB pathways, immune surveillance, and cell cycle regulation, or are transcription factors involved in B-cell development. Of particular interest are mutations and CNAs affecting S1P-activated pathways through S1PR1 or S1PR2, which likely regulate lymphoma cell migration and survival outside of follicles. Our custom gene enrichment panel provides high depth of coverage for the study of clonal evolution or divergence.

Mixed methods research is becoming more widely used in order to answer research questions and to investigate research problems in mental health and psychiatric nursing. However, two separate literature searches, one in Scotland and one in the USA, revealed that few mental health nursing studies identified mixed methods research in their titles. Many studies used the term 'embedded' but few studies identified in the literature were mixed methods embedded studies. The history, philosophical underpinnings, definition, types of mixed methods research and associated pragmatism are discussed, as well as the need for mixed methods research. Examples of mental health nursing mixed methods research are used to illustrate the different types of mixed methods: convergent parallel, embedded, explanatory and exploratory in their sequential and concurrent combinations. Implementing mixed methods research is also discussed briefly and the problem of identifying mixed methods research in mental and psychiatric nursing are discussed with some possible solutions to the problem proposed.