AfterImage:for baroque flute and fixed media

Commissioned by Sonic Arts Network and Huddersfield Contemporary Music Festival with funds from ACGB for Eleanor Dawson (flute)

Novel Panel Cointegration Tests Emending for Cross-Section Dependence with N Fixed

In this paper, we propose new cointegration tests for single equations and panels. Inboth cases, the asymptotic distributions of the tests, which are derived with N fixed andT → ∞, are shown to be standard normals. The effects of serial correlation and crosssectionaldependence are mopped out via long-run variances. An effective bias correctionis derived which is shown to work well in finite samples; particularly when N is smallerthan T. Our panel tests are robust to possible cointegration across units.

Design of a Dissolving Microneedle Platform for Transdermal Delivery of a Fixed-Dose Combination of Cardiovascular Drugs

Microneedles (MNs) are a minimally invasive drug delivery platform, designed to enhance transdermal drug delivery by breaching the stratum corneum. For the first time, this study describes the simultaneous delivery of a combination of three drugs using a dissolving polymeric MN system. In the present study, aspirin, lisinopril dihydrate, and atorvastatin calcium trihydrate were used as exemplar cardiovascular drugs and formulated into MN arrays using two biocompatible polymers, poly(vinylpyrrollidone) and poly(methylvinylether/maleic acid). Following fabrication, dissolution, mechanical testing, and determination of drug recovery from the MN arrays, in vitro drug delivery studies were undertaken, followed by HPLC analysis. All three drugs were successfully delivered in vitro across neonatal porcine skin, with similar permeation profiles achieved from both polymer formulations. An average of 126.3 ± 18.1 μg of atorvastatin calcium trihydrate was delivered, notably lower than the 687.9 ± 101.3 μg of lisinopril and 3924 ± 1011 μg of aspirin, because of the hydrophobic nature of the atorvastatin molecule and hence poor dissolution from the array. Polymer deposition into the skin may be an issue with repeat application of such a MN array, hence future work will consider more appropriate MN systems for continuous use, alongside tailoring delivery to less hydrophilic compounds.

Challenges of managing medications for older people at transition points of care

In clinical practice, pharmacists play a very important role in identifying and correcting medication discrepancies as older patients move across transition points of care. With increasing complexity of health care needs of older people, these discrepancies are likely to increase. The major concern with identifying and correcting medication discrepancies is that medication reconciliation is considered a retrospective problem – that is, dealing with medication discrepancies after they have occurred. It is argued here that a more proactive stance should be taken where doctors, nurses and pharmacists collectively work together to prevent medication discrepancies from happening in the first place. Improved involvement of patients and family members will help to facilitate better management of medications across transition points of care. Efficient use of information technology aids, such as electronic medication reconciliation tools, should also assist with organizational systems problems associated with the working culture, heavy workloads, and staff and skill mix of health professionals.

Care Leavers’ Experiences of Transition and Turning Points: Findings from a Biographical Narrative Study

This paper reports on the findings of a PhD research project that set out to explore how young people leaving out of home care experienced and made sense of their transition to adulthood. Using the Biographical Narrative Interpretative Method, in-depth accounts were collected and analysed for eight care leavers. The data suggest that in addition to care leavers living their lives as a series of biographical events, their ‘care career’, they also experience changes in the way they make sense of their lives which form a ‘subjective pathway’. Influenced by the literature on resilience, the research had anticipated that ‘turning point’ events would play a significant role in the young people’s subjective pathways. But the findings show a more gradual, phased shifting of subjectivity. It is suggested that legislation, policy, services and care practices need to facilitate this more drawn out ‘subjective pathway’. Attachment, resilience and humanistic social psychology are proposed as useful theoretical underpinnings for that work

The reliability of R50 as a measure of vulnerability of food webs to sequential species deletions

Recent studies predict elevated and accelerating rates of species extinctions over the 21st century, due to climate change and habitat loss. Considering that such primary species loss may initiate cascades of secondary extinctions and push systems towards critical tipping points, we urgently need to increase our understanding of if certain sequences of species extinctions can be expected to be more devastating than others Most theoretical studies addressing this question have used a topological (non-dynamical) approach to analyse the probability that food webs will collapse, below a fixed threshold value in species richness, when subjected to different sequences of species loss. Typically, these studies have neither considered the possibility of dynamical responses of species, nor that conclusions may depend on the value of the collapse threshold. Here we analyse how sensitive conclusions on the importance of different species are to the threshold value of food web collapse. Using dynamical simulations, where we expose model food webs to a range of extinction sequences, we evaluate the reliability of the most frequently used index, R<inf>50</inf>, as a measure of food web robustness. In general, we find that R<inf>50</inf> is a reliable measure and that identification of destructive deletion sequences is fairly robust, within a moderate range of collapse thresholds. At the same time, however, focusing on R<inf>50</inf> only hides a lot of interesting information on the disassembly process and can, in some cases, lead to incorrect conclusions on the relative importance of species in food webs.

Minimal residual disease detection in childhood acute lymphoblastic leukaemia patients at multiple time-points reveals high levels of concordance between molecular and immunophenotypic approaches

In this single centre study of childhood acute lymphoblastic leukaemia (ALL) patients treated on the Medical Research Council UKALL 97/99 protocols, it was determined that minimal residual disease (MRD) detected by real time quantitative polymerase chain reaction (RQ-PCR) and 3-colour flow cytometry (FC) displayed high levels of qualitative concordance when evaluated at multiple time-points during treatment (93.38%), and a combined use of both approaches allowed a multi time-point evaluation of MRD kinetics for 90% (53/59) of the initial cohort. At diagnosis, MRD markers with sensitivity of at least 0.01% were identified by RQ-PCR detection of fusion gene transcripts, IGH/TRG rearrangements, and FC. Using a combined RQ-PCR and FC approach, the evaluation of 367 follow-up BM samples revealed that the detection of MRD >1% at Day 15 (P = 0.04), >0.01% at the end of induction (P = 0.02), >0.01% at the end of consolidation (P = 0.01), >0.01% prior to the first delayed intensification (P = 0.01), and >0.1% prior to the second delayed intensification and continued maintenance (P = 0.001) were all associated with relapse and, based on early time-points (end of induction and consolidation) a significant log-rank trend (P = 0.0091) was noted between survival curves for patients stratified into high, intermediate and low-risk MRD groups.

POINTS OF VIEW: Multi-Roling Performance in Ireland in the 1990s, Part 1 (Layering)

This series of posts will consider the acting techniques required for this style of performance with reference to four productions from the 1990s in which two actors took on multiple roles: Frank Pig Says Hello (1992), Co-Motion’s stage adaptation of Pat McCabe’s novel; The Butcher Boy, Corca Dorca’s production of Disco Pigs (1996) by Enda Walsh; DubbleJoint’s production of Stones in his Pockets by Marie Jones (1996) and its subsequent award-winning revival which I produced at Belfast’s Lyric Theatre in 1999; and Kabosh’s production of Mojo Mickybo by Owen McCafferty (1998). The discussion will focus primarily on my own empirical exploration of the demands multi-roling places on an actor through the direction of recent revivals of Mojo Mickybo for Belfast’s Chatterbox Theatre Company (2013) and Bedlam Productions (2015).

Clinical end points for drug treatment trials in BCR-ABL1-negative classic myeloproliferative neoplasms: consensus statements from European LeukemiaNET (ELN) and Internation Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT)

The discovery of somatic mutations, primarily JAK2V617F and CALR, in classic BCR-ABL1-negative myeloproliferative neoplasms (MPNs) has generated interest in the development of molecularly targeted therapies, whose accurate assessment requires a standardized framework. A working group, comprised of members from European LeukemiaNet (ELN) and International Working Group for MPN Research and Treatment (IWG-MRT), prepared consensus-based recommendations regarding trial design, patient selection and definition of relevant end points. Accordingly, a response able to capture the long-term effect of the drug should be selected as the end point of phase II trials aimed at developing new drugs for MPNs. A time-to-event, such as overall survival, or progression-free survival or both, as co-primary end points, should measure efficacy in phase III studies. New drugs should be tested for preventing disease progression in myelofibrosis patients with early disease in randomized studies, and a time to event, such as progression-free or event-free survival should be the primary end point. Phase III trials aimed at preventing vascular events in polycythemia vera and essential thrombocythemia should be based on a selection of the target population based on new prognostic factors, including JAK2 mutation. In conclusion, we recommended a format for clinical trials in MPNs that facilitates communication between academic investigators, regulatory agencies and drug companies.