Obesity associated severe asthma represents a distinct clinical phenotype - Analysis of the British Thoracic Society Difficult Asthma Registry patient cohort according to body mass index

BACKGROUND: Obesity has emerged as a risk factor for the development of asthma and it may also influence asthma control and airways inflammation. However, the role of obesity in severe asthma remains unclear. OBJECTIVE: To explore the association between obesity (defined by BMI) and severe asthma. METHODS: Data from the National Registry for dedicated UK Difficult Asthma Services were used to compare patient demographics, disease characteristics and healthcare utilisation between three body mass index (BMI) categories (normal weight: 18.5 -24.99, overweight: 25 -29.99, obese: =30) in a well characterised group of severe asthmatic adults. RESULTS: The study population consisted of 666 severe asthmatics with a median BMI of 29.8 (interquartile range 22.5 -34.0). The obese group exhibited greater asthma medication requirements in terms of maintenance corticosteroid therapy (48.9% versus 40.4% and 34.5% in the overweight and normal weight groups, respectively), steroid burst therapy and short-acting ß2-agonist (SABA) use per day. Significant differences were seen with gastro-oesophageal reflux disease (GORD) (53.9% versus 48.1% and 39.7% in the overweight and normal weight groups, respectively) and proton pump inhibitor (PPI) use. Bone density scores were higher in the obese group, whilst pulmonary function testing revealed a reduced FVC and raised Kco. Serum IgE levels decreased with increasing BMI and the obese group were more likely to report eczema, but less likely to have a history of nasal polyps. CONCLUSIONS: Severe asthmatics display particular characteristics according to BMI that support the view that obesity associated severe asthma may represent a distinct clinical phenotype.1Royal Brompton Hospital, London, UK;2Department of Computing, Imperial College, UK3Airways Disease, National Heart & Lung Institute, Imperial College, UK;4Centre for infection and immunity, Queen's University of Belfast, UK;5University of Leicester, UK;6The University of Manchester and University Hospital of South Manchester, UK;7Birmingham Heartlands Hospital, University of Birmingham, UK;8Gartnavel General Hospital, University of Glasgow, UK;9Glasgow Royal Infirmary, Glasgow, UKCorrespondence: Dr Andrew N. Menzies-Gow, Royal Brompton Hospital, Fulham Road, London SW3 6HP.

Modelling the control of interceptive actions

In recent years, several phenomenological dynamical models have been formulated that describe how perceptual variables are incorporated in the control of motor variables. We call these short-route models as they do not address how perception-action patterns might be constrained by the dynamical properties of the sensory, neural and musculoskeletal subsystems of the human action system. As an alternative, we advocate a long-route modelling approach in which the dynamics of these subsystems are explicitly addressed and integrated to reproduce interceptive actions. The approach is exemplified through a discussion of a recently developed model for interceptive actions consisting of a neural network architecture for the online generation of motor outflow commands, based on time-to-contact information and information about the relative positions and velocities of hand and ball. This network is shown to be consistent with both behavioural and neurophysiological data. Finally, some problems are discussed with regard to the question of how the motor outflow commands (i.e. the intended movement) might be modulated in view of the musculoskeletal dynamics.

Prospective control of manual interceptive actions:comparative simulations of extant and new model constructs

Two prospective controllers of hand movements in catching-both based on required velocity control-were simulated. Under certain conditions, this required velocity control led to overshoots of the future interception point. These overshoots were absent in pertinent experiments. To remedy this shortcoming, the required velocity model was reformulated in terms of a neural network, the Vector Integration To Endpoint model, to create a Required Velocity Integration To Endpoint model. Addition of a parallel relative velocity channel, resulting in the Relative and Required Velocity Integration To Endpoint model, provided a better account for the experimentally observed kinematics than the existing, purely behavioral models. Simulations of reaching to intercept decelerating and accelerating objects in the presence of background motion were performed to make distinct predictions for future experiments.

Which is the Only Game in Town? Minority Rights Issues in Estonia and Slovakia During and after EU Accession:Perspectives on European Politics and Society

Post-communist transition went hand in hand with the European integration process. Much of the literature on EU accession focuses on the rational decision to implement a set of European norms into domestic legislation pre-accession. It is often concluded that once EU membership is achieved, states succumb their rationality and act on the basis of internalised norms. The paper claims that the past literature overlooks the wider framework within which policy-makers operate before and after the accession, namely domestic sovereignty over policy-making and implementation. Tracing the policy dynamics in the area of minority rights in Estonia and Slovakia, we demonstrate that the European integration ushered greater domestic control over policy implementation on minority issues in two states exposed to a heavy dose of conditionality. As we observe, both states have consolidated their state- and nation-building policies referencing EU conditionality in the course of accession and later EU membership to assert centrality of domestic objectives for policy-making and implementation.

Product standardisation as a tool to control prescribing costs a case study of alginate liquid preparations

Introduction Product standardisation involves promoting the prescribing of pre-selected products within a particular category across a healthcare region and is designed to improve patient safety by promoting continuity of medicine use across the primary/secondary care interface, in addition to cost containment without compromising clinical care (i.e. maintaining safety and efficacy). Objectives To examine the impact of product standardisation on the prescribing of compound alginate preparations within primary care in Northern Ireland. Methods Data were obtained on alginate prescribing from the Northern Ireland Central Services Agency (Prescription Pricing Branch), covering a period of 43 months. Two standardisation promotion interventions were carried out at months 18 and 33. In addition to conventional statistical analyses, a simple interrupted time series analysis approach, using graphical interpretation, was used to facilitate interpretation of the data. Results There was a significant increase in the prescribed share of the preferred alginate product in each of the four health boards in Northern Ireland and a decrease in the cost per Defined Daily Dose for alginate liquid preparations overall. Compliance with the standardisation policy was, however, incomplete and was influenced to a marked degree by the activities of the pharmaceutical industry. The overall economic impact of the prescribing changes during the study was small (3.1%). Conclusion The findings suggested that product standardisation significantly influenced the prescribing pattern for compound alginate liquid preparations within primary care across Northern Ireland. © 2012 The Authors. IJPP © 2012 Royal Pharmaceutical Society.

A statistical process control approach for automatic anti-islanding detection using synchrophasors

Anti-islanding protection is becoming increasingly important due to the rapid installation of distributed generation from renewable resources like wind, tidal and wave, solar PV, bio-fuels, as well as from other resources like diesel. Unintentional islanding presents a potential risk for damaging utility plants and equipment connected from the demand side, as well as to public and personnel in utility plants. This paper investigates automatic islanding detection. This is achieved by deploying a statistical process control approach for fault detection with the real-time data acquired through a wide area measurement system, which is based on Phasor Measurement Unit (PMU) technology. In particular, the principal component analysis (PCA) is used to project the data into principal component subspace and residual space, and two statistics are used to detect the occurrence of fault. Then a fault reconstruction method is used to identify the fault and its development over time. The proposed scheme has been used in a real system and the results have confirmed that the proposed method can correctly identify the fault and islanding site.

GPCR structure, function, drug discovery and crystallography: report from Academia-Industry International Conference (UK Royal Society) Chicheley Hall, 1-2 September 2014

G-protein coupled receptors (GPCRs) are the targets of over half of all prescribed drugs today. The UniProt database has records for about 800 proteins classified as GPCRs, but drugs have only been developed against 50 of these. Thus, there is huge potential in terms of the number of targets for new therapies to be designed. Several breakthroughs in GPCRs biased pharmacology, structural biology, modelling and scoring have resulted in a resurgence of interest in GPCRs as drug targets. Therefore, an international conference, sponsored by the Royal Society, with world-renowned researchers from industry and academia was recently held to discuss recent progress and highlight key areas of future research needed to accelerate GPCR drug discovery. Several key points emerged. Firstly, structures for all three major classes of GPCRs have now been solved and there is increasing coverage across the GPCR phylogenetic tree. This is likely to be substantially enhanced with data from x-ray free electron sources as they move beyond proof of concept. Secondly, the concept of biased signalling or functional selectivity is likely to be prevalent in many GPCRs, and this presents exciting new opportunities for selectivity and the control of side effects, especially when combined with increasing data regarding allosteric modulation. Thirdly, there will almost certainly be some GPCRs that will remain difficult targets because they exhibit complex ligand dependencies and have many metastable states rendering them difficult to resolve by crystallographic methods. Subtle effects within the packing of the transmembrane helices are likely to mask and contribute to this aspect, which may play a role in species dependent behaviour. This is particularly important because it has ramifications for how we interpret pre-clinical data. In summary, collaborative efforts between industry and academia have delivered significant progress in terms of structure and understanding of GPCRs and will be essential for resolving problems associated with the more difficult targets in the future.

Biological control of the fish louse in a rainbow trout fishery

Novel egg-laying boards were found to be effective in the biological control of the freshwater fish louse Argulus foliaceus in a 12.9 ha rainbow trout Oncorhynchus mykiss fishery which had a high prevalence and intensity of infection of juvenile parasites in the early spring of 1999. Approximately 228 000d during an extensive 14 week period of egg laying which peaked in June 1999. In contrast, only 1566 clutches were harvested in 2000, when egg laying activity showed a bi-modal distribution, peaking in May and again in July and August. iaceus on rainbow trout in consecutive years was 2.9 : 1 and 2.1 : 1. Estimates of the size of the female A. foliaceus population based on egg-laying activity in 1999 exceeded that derived from measurements of prevalence and intensity of infection, whereas in 2000, this was more in balance. A minimum temperature of 10 degree C was identified for egg laying, which occurred continuously from May to October in a broadly synchronous manner.. Copyright 2002 The Fisheries Society of the British Isles

Control of harmonic generation from relativistic mirrors

We demonstrate for the first time that fine varying of the density gradient of a plasma mirror along with laser spatial phase on target allows total control over the harmonic generation mechanisms and harmonic spatial properties. An analytical model is also proposed. © OSA 2013.

Complete control of high-harmonic generation for high average power applications

We present a new dual-gas multi-jet HHG source which can be perfectly controlled via phasematching of the long and short trajectory contributions and is applicable for high average power driver laser systems. © 2011 Optical Society of America.