Quality of Life Changes Following Peripheral Blood Stem Cell Transplantation and Participation in a Mixed-Type, Moderate-intensity, Exercise Program

Summary:The purpose of this investigation was to evaluate the impact of undertaking peripheral blood stem cell transplantation (PBST) on quality of life (QoL), and to determine the effect of participating in a mixed-type, moderate-intensity exercise program on QoL. It was also an objective to determine the relationship between peak aerobic capacity and QoL in PBST patients. QoL was assessed via the CARES questionnaire and peak aerobic capacity by a maximal graded treadmill test, pretransplant (PI), post transplant (PII) and following a 12-week intervention period (PIII). At PII, 12 patients were divided equally into a control or exercise intervention group. Undergoing a PBST was associated with a statistically but not clinically significant decline in QoL (P<0.05). Following the intervention, exercising patients demonstrated an improved QoL when compared with pretransplant ratings (P<0.01) and nonexercising transplant patients (P<0.05). Moreover, peak aerobic capacity and QoL were correlated (P<0.05). The findings demonstrated that exercise participation following oncology treatment is associated with a reduction in the number and severity of endorsed problems, which in turn leads to improvements in global, physical and psychosocial QoL. Furthermore, a relationship between fitness and QoL exists, with those experiencing higher levels of fitness also demonstrating higher QoL.Bone Marrow Transplantation (2004) 33, 553-558. doi:10.1038/sj.bmt.1704378 Published online 12 January 200

Polycomb Target Genes Are Silenced in Multiple Myeloma

Multiple myeloma (MM) is a genetically heterogeneous disease, which to date remains fatal. Finding a common mechanism for initiation and progression of MM continues to be challenging. By means of integrative genomics, we identified an underexpressed gene signature in MM patient cells compared to normal counterpart plasma cells. This profile was enriched for previously defined H3K27-tri-methylated genes, targets of the Polycomb group (PcG) proteins in human embryonic fibroblasts. Additionally, the silenced gene signature was more pronounced in ISS stage III MM compared to stage I and II. Using chromatin immunoprecipitation (ChIP) assay on purified CD138+ cells from four MM patients and on two MM cell lines, we found enrichment of H3K27me3 at genes selected from the profile. As the data implied that the Polycomb-targeted gene profile would be highly relevant for pharmacological treatment of MM, we used two compounds to chemically revert the H3K27-tri-methylation mediated gene silencing. The S-adenosylhomocysteine hydrolase inhibitor 3-Deazaneplanocin (DZNep) and the histone deacetylase inhibitor LBH589 (Panobinostat), reactivated the expression of genes repressed by H3K27me3, depleted cells from the PRC2 component EZH2 and induced apoptosis in human MM cell lines. In the immunocompetent 5T33MM in vivo model for MM, treatment with LBH589 resulted in gene upregulation, reduced tumor load and increased overall survival. Taken together, our results reveal a common gene signature in MM, mediated by gene silencing via the Polycomb repressor complex. The importance of the underexpressed gene profile in MM tumor initiation and progression should be subjected to further studies

Single cell dissection of plasma cell heterogeneity in symptomatic and asymptomatic myeloma

Multiple myeloma, a plasma cell malignancy, is the second most common blood cancer. Despite extensive research, disease heterogeneity is poorly characterized, hampering efforts for early diagnosis and improved treatments. Here, we apply single cell RNA sequencing to study the heterogeneity of 40 individuals along the multiple myeloma progression spectrum, including 11 healthy controls, demonstrating high interindividual variability that can be explained by expression of known multiple myeloma drivers and additional putative factors. We identify extensive subclonal structures for 10 of 29 individuals with multiple myeloma. In asymptomatic individuals with early disease and in those with minimal residual disease post-treatment, we detect rare tumor plasma cells with molecular characteristics similar to those of active myeloma, with possible implications for personalized therapies. Single cell analysis of rare circulating tumor cells allows for accurate liquid biopsy and detection of malignant plasma cells, which reflect bone marrow disease. Our work establishes single cell RNA sequencing for dissecting blood malignancies and devising detailed molecular characterization of tumor cells in symptomatic and asymptomatic patients

Beyond Verbal Narratives: Using Timeline Images in the Semiotic Cultural Study of Meaning Making

Contemporary semiotic cultural tradition in psychology views human meaning making as unfolding through the negotiation of multiple real and imagined scenarios and storylines. While emphasising this complex and layered nature of meaning making, this research tradition offers little methodological guidance for appreciating and evidencing this multiplicity in data analysis and interpretation. This paper suggests that a methodological approach that combines visual and verbal ways of representing one’s personal stories might offer a useful alternative for evidencing the multiple meanings that individuals create about their personal journeys. By presenting two examples of drawn timeline images and corresponding interview extracts, the paper discusses how the chosen methodological approach offered opportunities for participants to ‘show and tell’ their complex and layered stories, and gave them freedom and agency to shape the research encounter and data production processes. The paper also highlights how the incorporation of visual methods into the methodology enabled the researcher to find alternative ways of interpreting participants’ stories. The paper argues for a purposeful integration of visual and verbal methods, where the semiotic tensions and clashes between these modes can reveal novel ways of seeing researchers’ and participants’ meanings in the making

Leadership values, trust and negative capability: Managing the uncertainties of future English Higher Education

The complex leadership attribute of ‘negative capability’ in managing uncertainty and engendering trust may be amongst the qualities enabling institutions to cope with multiple recent government policy challenges affecting English higher education, including significant increases in student fees. Research findings are reported on changes in leadership values, trust and organisational cultures in higher education during the current ‘age of austerity’. Data from university experts, managers and academics in semi-structured interviews were informed by questionnaires (n = 16), online surveys (n = 121) and a focus group (n = 6). Findings indicated that values-based leadership characterised by skilful ‘negative capability’ is now needed in English higher education. ‘Negative capability’ is defined as the ability to resist the ‘false necessity’ of deterministic solutions in building staff trust to cope proactively with ambiguity and change. This capability is needed for academic leaders to maintain their role in shaping the enduring purposes of higher education during a recession, both in England and in the wider international environment