Compact fusion

There are many advantages to writing functional programs in a compositional style, such as clarity and modularity. However, the intermediate data structures produced may mean that the resulting program is inefficient in terms of space. These may be removed using deforestation techniques, but whether the space performance is actually improved depends upon the structures being consumed in the same order that they are produced. In this paper we explore this problem for the case when the intermediate structure is a list, and present a solution. We then formalise the space behaviour of our solution by means of program transformation techniques and the use of abstract machines

Switching patients from other inhaled corticosteroid devices to the Easyhaler(®) : historical, matched-cohort study of real-life asthma patients

Peer reviewedPublisher PD

Reflections on Participation in the Birmingham Law School Pro Bono Group

This paper collates presentations made by four student volunteer members of the Birmingham Law School Pro Bono Group during National Pro Bono Week 2017

Management of COPD in the UK primary-care setting : an analysis of real-life prescribing patterns

Peer reviewedPublisher PD

Routine care of peripheral intravenous catheters versus clinically indicated replacement: randomised controlled trial

Objective To compare routine replacement of intravenous peripheral catheters with replacement only when clinically indicated

ASL-incorporated pharmacokinetic modelling of PET data with reduced acquisition time: Application to amyloid imaging

Pharmacokinetic analysis of Positron Emission Tomography (PET) data typically requires at least one hour of image acquisition, which poses a great disadvantage in clinical practice. In this work, we propose a novel approach for pharmacokinetic modelling with significantly reduced PET acquisition time, by incorporating the blood flow information from simultaneously acquired arterial spin labelling (ASL) magnetic resonance imaging (MRI). A relationship is established between blood flow, measured by ASL, and the transfer rate constant from plasma to tissue of the PET tracer, leading to modified PET kinetic models with ASL-derived flow information. Evaluation on clinical amyloid imaging data from an Alzheimer’s disease (AD) study shows that the proposed approach with the simplified reference tissue model can achieve amyloid burden estimation from 30 min [18F]florbetapir PET data and 5 min simultaneous ASL MR data, which is comparable with the estimation from 60 min PET data (mean error=−0.03). Conversely, standardised uptake value ratio (SUVR), the alternative measure from the data showed a positive bias in areas of higher amyloid burden (mean error=0.07)

The languages of peace during the French religious wars

The desirability of peace was a common topos in sixteenth-century political rhetoric, and the duty of the king to uphold the peace for the benefit of his subjects was also a long-established tradition. However, the peculiar circumstances of the French religious wars, and the preferred royal policy of pacification, galvanized impassioned debate among both those who supported and those who opposed confessional coexistence. This article looks at the diverse ways in which peace was viewed during the religious wars through an exploration of language and context. It draws not only on the pronouncements of the crown and its officials, and of poets and jurists, but also on those of local communities and confessional groups. Opinion was not just divided along religious lines; political imperatives, philosophical positions and local conditions all came into play in the arguments deployed. The variegated languages of peace provide a social and cultural dimension for the contested nature of sixteenth-century French politics. However, they could not restore harmony to a war-torn and divided kingdom

Characteristics of patients making serious inhaler errors with a dry powder inhaler and association with asthma-related events in a primary care setting

Acknowledgements The iHARP database was funded by unrestricted grants from Mundipharma International Ltd and Research in Real-Life Ltd; these analyses were funded by an unrestricted grant from Teva Pharmaceuticals. Mundipharma and Teva played no role in study conduct or analysis and did not modify or approve the manuscript. The authors wish to direct a special appreciation to all the participants of the iHARP group who contributed data to this study and to Mundipharma, sponsors of the iHARP group. In addition, we thank Julie von Ziegenweidt for assistance with data extraction and Anna Gilchrist and Valerie L. Ashton, PhD, for editorial assistance. Elizabeth V. Hillyer, DVM, provided editorial and writing support, funded by Research in Real-Life, Ltd.Peer reviewedPublisher PD

TP53 mutant MDM2-amplified cell lines selected for resistance to MDM2-p53 binding antagonists retain sensitivity to ionizing radiation

Non-genotoxic reactivation of the p53 pathway by MDM2-p53 binding antagonists is an attractive treatment strategy for wild-type TP53 cancers. To determine how resistance to MDM2/p53 binding antagonists might develop, SJSA-1 and NGP cells were exposed to growth inhibitory concentrations of chemically distinct MDM2 inhibitors, Nutlin-3 and MI-63, and clonal resistant cell lines generated. The p53 mediated responses of parental and resistant cell lines were compared. In contrast to the parental cell lines, p53 activation by Nutlin-3, MI-63 or ionizing radiation was not observed in either the SJSA-1 or the NGP derived cell lines. An identical TP53 mutation was subsequently identified in both of the SJSA-1 resistant lines, whilst one out of three identified mutations was common to both NGP derived lines. Mutation specific PCR revealed these mutations were present in parental SJSA-1 and NGP cell populations at a low frequency. Despite cross-resistance to a broad panel of MDM2/p53 binding antagonists, these MDM2-amplified and TP53 mutant cell lines remained sensitive to ionizing radiation (IR). These results indicate that MDM2/p53 binding antagonists will select for p53 mutations present in tumours at a low frequency at diagnosis, leading to resistance, but such tumours may nevertheless remain responsive to alternative therapies, including IR

Comparison of serious inhaler technique errors made by device-naïve patients using three different dry powder inhalers: a randomised, crossover, open-label study

Background: Serious inhaler technique errors can impair drug delivery to the lungs. This randomised, crossover, open-label study evaluated the proportion of patients making predefined serious errors with Pulmojet compared with Diskus and Turbohaler dry powder inhalers. Methods: Patients ≥18 years old with asthma and/or COPD who were current users of an inhaler but naïve to the study devices were assigned to inhaler technique assessment on Pulmojet and either Diskus or Turbohaler in a randomised order. Patients inhaled through empty devices after reading the patient information leaflet. If serious errors potentially affecting dose delivery were recorded, they repeated the inhalations after watching a training video. Inhaler technique was assessed by a trained nurse observer and an electronic inhalation profile recorder. Results: Baseline patient characteristics were similar between randomisation arms for the Pulmojet-Diskus (n = 277) and Pulmojet-Turbohaler (n = 144) comparisons. Non-inferiority in the proportions of patients recording no nurse-observed serious errors was demonstrated for both Pulmojet versus Diskus, and Pulmojet versus Turbohaler; therefore, superiority was tested. Patients were significantly less likely to make ≥1 nurse-observed serious errors using Pulmojet compared with Diskus (odds ratio, 0.31; 95 % CI, 0.19–0.51) or Pulmojet compared with Turbohaler (0.23; 0.12–0.44) after reading the patient information leaflet with additional video instruction, if required. Conclusions These results suggest Pulmojet is easier to learn to use correctly than the Turbohaler or Diskus for current inhaler users switching to a new dry powder inhaler