Risk of myeloid neoplasms after solid organ transplantation

Solid organ transplant recipients have elevated cancer risks, owing in part to pharmacologic immunosuppression. However, little is known about risks for hematologic malignancies of myeloid origin. We linked the US Scientific Registry of Transplant Recipients with 15 population-based cancer registries to ascertain cancer occurrence among 207 859 solid organ transplants (1987–2009). Solid organ transplant recipients had a significantly elevated risk for myeloid neoplasms, with standardized incidence ratios (SIRs) of 4.6 (95% confidence interval 3.8–5.6; N=101) for myelodysplastic syndromes (MDS), 2.7 (2.2–3.2; N=125) for acute myeloid leukemia (AML), 2.3 (1.6–3.2; N=36) for chronic myeloid leukemia and 7.2 (5.4–9.3; N=57) for polycythemia vera. SIRs were highest among younger individuals and varied by time since transplantation and organ type (Poisson regression P<0.05 for all comparisons). Azathioprine for initial maintenance immunosuppression increased risk for MDS (P=0.0002) and AML (2–5 years after transplantation, P=0.0163). Overall survival following AML/MDS among transplant recipients was inferior to that of similar patients reported to US cancer registries (log-rank P<0.0001). Our novel finding of increased risks for specific myeloid neoplasms after solid organ transplantation supports a role for immune dysfunction in myeloid neoplasm etiology. The increased risks and inferior survival should heighten clinician awareness of myeloid neoplasms during follow-up of transplant recipients.

An efficacy and mechanism evaluation study of Levosimendan for the Prevention of Acute oRgan Dysfunction in Sepsis (LeoPARDS): Protocol for a randomized controlled trial

Background

Organ dysfunction consequent to infection (‘severe sepsis’) is the leading cause of admission to an intensive care unit (ICU). In both animal models and early clinical studies the calcium channel sensitizer levosimendan has been demonstrated to have potentially beneficial effects on organ function. The aims of the Levosimendan for the Prevention of Acute oRgan Dysfunction in Sepsis (LeoPARDS) trial are to identify whether a 24-hour infusion of levosimendan will improve organ dysfunction in adults who have septic shock and to establish the safety profile of levosimendan in this group of patients.

This is a multicenter, randomized, double-blind, parallel group, placebo-controlled trial. Adults fulfilling the criteria for systemic inflammatory response syndrome due to infection, and requiring vasopressor therapy, will be eligible for inclusion in the trial. Within 24 hours of meeting these inclusion criteria, patients will be randomized in a 1:1 ratio stratified by the ICU to receive either levosimendan (0.05 to 0.2 μg.kg^-1.min^-1 or placebo for 24 hours in addition to standard care. The primary outcome measure is the mean Sequential Organ Failure Assessment (SOFA) score while in the ICU. Secondary outcomes include: central venous oxygen saturations and cardiac output; incidence and severity of renal failure using the Acute Kidney Injury Network criteria; duration of renal replacement therapy; serum bilirubin; time to liberation from mechanical ventilation; 28-day, hospital, 3 and 6 month survival; ICU and hospital length-of-stay; and days free from catecholamine therapy. Blood and urine samples will be collected on the day of inclusion, at 24 hours, and on days 4 and 6 post-inclusion for investigation of the mechanisms by which levosimendan might improve organ function. Eighty patients will have additional blood samples taken to measure levels of levosimendan and its active metabolites OR-1896 and OR-1855. A total of 516 patients will be recruited from approximately 25 ICUs in the United Kingdom.

This trial will test the efficacy of levosimendan to reduce acute organ dysfunction in adult patients who have septic shock and evaluate its biological mechanisms of action.

Developing dance music from the song tradition

This paper takes an historical look at the development of now popular Irish dance tunes which originated in or passed through the song tradition. It discusses the role of what I have termed ‘intermediaries’ which bridge the gap between the song and dance music traditions, allowing repertoire to flow between these two tributary streams of the modern tradition. I will discuss the under-investigated practice of lilting, which I will argue has acted as an important intermediary between the dance and song traditions, particularly in the eighteenth century. before going on to discuss some examples of songs and dance tunes which have a more complex relationship.

Recruiting Participants for Randomized Controlled Trials of Music Therapy: A Practical Illustration

Background: Failure to recruit sufficient numbers of participants to randomized controlled trials is a common and serious problem. This problem may be additionally acute in music therapy research.

Objective: To use the experience of conducting a large randomized controlled trial of music therapy for young people with emotional and behavioral difficulties to illustrate the strategies that can be used to optimize recruitment; to report on the success or otherwise of those strategies; and to draw general conclusions about the most effective approaches.

Methods: Review of the methodological literature, and a narrative account and realist analysis of the recruitment process.

Results: The strategies adopted led to the achievement of the recruitment target of 250 subjects, but only with an extension to the recruitment period. In the pre-protocol stage of the research, these strategies included the engagement of non-music therapy clinical investigators, and extensive consultation with clinical stakeholders. In the protocol development and initial recruitment stages, they involved a search of systematic reviews of factors leading to under-recruitment and of interventions to promote recruitment, and the incorporation of their insights into the research protocol and practices. In the latter stages of recruitment, various stakeholders including clinicians, senior managers and participant representatives were consulted in an attempt to uncover the reasons for the low recruitment levels that the research was experiencing.

Conclusions: The primary mechanisms to promote recruitment are education, facilitation, audit and feedback, and time allowed. The primary contextual factors affecting the effectiveness of these mechanisms are professional culture and organizational support.

Colloquium on Sound and Music

Invited participation in a colloquium on Sound and Music at CREATIVE RESEARCH INTO SOUND ARTS PRACTICE unit of the London College of Communication.

Belfast's Traditional Music Scene: A Narrative of Change and Development

Today Belfast is home to a vibrant traditional music scene. There have never been more sessions, concerts, classes or lectures devoted to traditional music in the north's biggest city. A complex system of promoters, performers and listeners has emerged in a city that is growing in confidence as it moves away from the dark days of the Troubles. But how does this system function? While Dowling (2014) has examined the development of traditional music-making in Belfast as it shifted from a pre-conflict to conflict ridden environment, little research has been carried out into the reasons behind the boom in traditional music-making in a post-conflict setting.

This paper examines the impact upon the traditional music scene of the first wave of students to arrive in Belfast after the signing of the Good Friday Agreement in 1998. These musicians, such as Donal O'Connor, Ruadhrai O'Kane and Aidan Walsh have had a lasting impact upon the lives of musicians native to Belfast, helping to bring traditional music to new venues and audiences.

The work of Belfast-based music schools with varying remits, such as Belfast Trad., and the Andersonstown School of Traditional and Contemporary Music, is also examined for the purpose of illustrating how both adults and young people are being educated about their musical heritage.

To be inside someone else's dream: On Music for Sleeping & Waking Minds

Music for Sleeping & Waking Minds (2011-2012) is a new,overnight work in which four performers fall asleep while wearing custom designed EEG sensors which monitor their brainwave activity. The data gathered from the EEG sensors is applied in real time to different audio and image signal processing functions, resulting in continuously evolving multichannel sound environment and visual projection. This material serves as an audiovisual description of the individual and collective neuro physiological state of the ensemble. Audiences are invited to experience the work in different states of attention: while alert and asleep, resting and awakening.

Compositional and Performance Mapping in Computer Chamber Music: A Case Study

The mapping problem is inherent to digital musical instruments (DMIs), which require, at the very least, an association between physical gestures and digital synthesis algorithms to transform human bodily performance into sound. This article considers the DMI mapping problem in the context of the creation and performance of a heterogeneous computer chamber music piece, a trio for violin, biosensors, and computer. Our discussion situates the DMI mapping problem within the broader set of interdependent musical interaction issues that surfaced during the composition and rehearsal of the trio. Through descriptions of the development of the piece, development of the hardware and software interfaces, lessons learned through rehearsal, and self-reporting by the participants, the rich musical possibilities and technical challenges of the integration of digital musical instruments into computer chamber music are demonstrated.