Mutational analysis of disease relapse in patients allografted for acute myeloid leukemia

Disease relapse is the major cause of treatment failure after allogeneic stem cell transplantation (allo-SCT) in acute myeloid leukemia (AML). To identify AML-associated genes prognostic of AML relapse post–allo-SCT, we resequenced 35 genes in 113 adults at diagnosis, 49 of whom relapsed. Two hundred sixty-two mutations were detected in 102/113 (90%) patients. An increased risk of relapse was observed in patients with mutations in WT1 (P = .018), DNMT3A (P = .045), FLT3 ITD (P = .071), and TP53 (P = .06), whereas mutations in IDH1 were associated with a reduced risk of disease relapse (P = .018). In 29 patients, we additionally compared mutational profiles in bone marrow at diagnosis and relapse to study changes in clonal structure at relapse. In 13/29 patients, mutational profiles altered at relapse. In 9 patients, mutations present at relapse were not detected at diagnosis. In 15 patients, additional available pre–allo-SCT samples demonstrated that mutations identified posttransplant but not at diagnosis were detectable immediately prior to transplant in 2 of 15 patients. Taken together, these observations, if confirmed in larger studies, have the potential to inform the design of novel strategies to reduce posttransplant relapse highlighting the potential importance of post–allo-SCT interventions with a broad antitumor specificity in contrast to targeted therapies based on mutational profile at diagnosis

Astonish Me! Recalling the Cabaret Spirit

Program for the 1999 RISD Wintersessoin Cabaret intiated by the Image and Word class in collaboration with students of RISD Cabaret 1998 and held at AS220. The presentation was conceived and performed in homage and celebration of past RISD Cabaret shows 1987-1998. Graphic Design: Ron Winter, Ji-Ho Sohn and Eric Urban.https://digitalcommons.risd.edu/liberalarts_cabaret_programs/1010/thumbnail.jp

Feminist Economics, Setting out the Parameters

___Introduction___ Feminist economics has developed its position over the past decade, towards a firmer embeddedness in economic science and a source of inspiration for activists, policy makers, and social science researchers in a wide variety of fields of research. This development has come about in a relatively short period of time, as is reflected, for example, in the follow-up book of the feminist economic primer Beyond Economic Man (Ferber/Nelson 1993), published ten years later: Feminist Economics Today (Ferber/Nelson, 2003) The strengthened position of feminist economics also shows in the 10-year anniversary of the prize-winning journal Feminist Economics, the flourishing of the International Association for Feminist Economics (IAFFE), as well as the more regular demand for feminist economic policy advise by institutions like the UN, OECD and governments in developed and developing countries, and in well-established training courses in feminist economics, such as at the Institute of Social Studies and University of Utah . It is impossible to give a fair overview of the state of the art of feminist economics in the number of pages available, even when limited to issues pertaining to development and macroeconomics . As a consequence, this is a very sketchy and subjective overview of what I perceive to be recent developments in feminist economics that have relevance for feminist development analysis and policy. The next section recognizes three trends in feminist economics, in particular the engagement of feminist economists with heterodox schools of economics. The following sections will briefly review developments in methodology and methods in feminist economics. These will be followed by three sections on topics that have recently become key themes or areas of research in feminist economics, in particular in the area of development economics: unpaid labour and the care economy; the two-way relationship between gender and trade; and gender, efficiency and growth. Each of these topics will be introduced, with references to the main literature, and some links to policy recommendations. The paper will end with a conclusion

Calling for help: a responsive evaluation of Child Health Line

The project examined the responsiveness of the telenursing service provided by the Child Health Line (hereinafter referred to as CHL). It aimed to provide an account of population usage of the service, the call request types and the response of the service to the calls. In so doing, the project extends the current body of knowledge pertaining to the provision of parenting support through telenursing. Approximately 900 calls to the CHL were audio-recorded over the December 2005-2006 Christmas-New Year period. A protocol was developed to code characteristics of the call, the interactional features between the caller and nurse call-taker, and the extent to which there was (a) agreement on problem definition and the plan of action and (b) interactional alignment between nurse and caller. A quantitative analysis examined the frequencies of the main topics covered in calls to the CHL and any statistical associations between types of calls, length of calls and nurse-caller alignment. In addition, a detailed qualitative analysis was conducted on a subset of calls dealing with the nurse management of calls seeking medical advice and information. Key findings include: • Overall, 74% of the calls discussed parenting and child development issues, 48% discussed health/medical issues, and 16% were information-seeking calls. • More specifically: o 21% discussed health/medical and parenting and child development issues. o 3% discussed parenting and information-seeking issues. o 5% discussed health/medical, parenting/development and information issues. o 18% exclusively focussed on health and medical issues and therefore were outside the remit of the intended scope of the CHL. These calls caused interactional dilemmas for the nurse call-takers as they simultaneously dealt with parental expectations for help and the CHL guidelines indicating that offering medical advice was outside the remit of the service. • Most frequent reasons for calling were to discuss sleep, feeding, normative infant physical functions and parenting advice. • The average length of calls to the CHL was 7 minutes. • Longer calls were more likely to involve nurse call-takers giving advice on more than one topic, the caller displaying strong emotions, the caller not specifically providing the reason for the call, and the caller discussing parenting and developmental issues. • Shorter calls were characterised by the nurse suggesting that the child receive immediate medical attention, the nurse emphasising the importance or urgency of the plan of action, the caller referring to or requesting confirmation of a diagnosis, and caller and nurse call-taker discussion of health and medical issues. • The majority of calls, 92%, achieved parent-nurse alignment by the conclusion of the call. However, 8% did not. • The 8% of calls that were not aligned require further quantitative and qualitative investigation of the interactional features. The findings are pertinent in the current context where Child Health Line now resides within 13HEALTH. These findings indicate: 1. A high demand for parenting advice. 2. Nurse call-takers have a high level of competency in dealing with calls about parenting and normal child development, which is the remit of the CHL. 3. Nurse call-takers and callers achieve a high degree of alignment when both parties agree on a course of action. 4. There is scope for developing professional practice in calls that present difficulties in terms of call content, interactional behaviour and call closure. Recommendations of the project: 1. There are numerous opportunities for further research on interactional aspects of calls to the CHL, such as further investigations of the interactional features and the association of the features to alignment and nonalignment. The rich and detailed insights into the patterns of nurse-parent interactions were afforded by the audio-recording and analysis of calls to the CHL. 2. The regular recording of calls would serve as a way of increasing understanding of the type and nature of calls received, and provide a valuable training resource. Recording and analysing calls to CHL provides insight into the operation of the service, including evidence about the effectiveness of triaging calls. 3. Training in both recognising and dealing with problem calls may be beneficial. For example, calls where the caller showed strong emotion, appeared stressed, frustrated or troubled were less likely to be rated as aligned calls. In calls where the callers described being ‘at their wits end’, or responded to each proposed suggestion with ‘I’ve tried that’, the callers were fairly resistant to advice-giving. 4. Training could focus on strategies for managing calls relating to parenting support and advice, and parental well-being. The project found that these calls were more likely to be rated as being nonaligned. 5. With the implementation of 13HEALTH, future research could compare nurse-parent interaction following the implementation of triaging. Of the calls, 21% had both medical and parenting topics discussed and 5.3% discussed medical, parenting and information topics. Added to this, in 12% of calls, there was ambiguity between the caller and nurse call-taker as to whether the problem was medical or behavioural

Clinical Grade Regulatory CD4+ T Cells (Tregs): Moving Toward Cellular-Based Immunomodulatory Therapies

Regulatory T cells (Tregs) are CD4+ T cells that are key players of immune tolerance. They are powerful suppressor cells, able to impact the function of numerous immune cells, including key effectors of inflammation such as effector T cells. For this reason, Tregs are an ideal candidate for the development of cell therapy approaches to modulate immune responses. Treg therapy has shown promising results so far, providing key knowledge on the conditions in which these cells can provide protection and demonstrating that they could be an alternative to current pharmacological immunosuppressive therapies. However, a more comprehensive understanding of their characteristics, isolation, activation, and expansion is needed to be able design cost effective therapies. Here, we review the practicalities of making Tregs a viable cell therapy, in particular, discussing the challenges faced in isolating and manufacturing Tregs and defining what are the most appropriate applications for this new therapy