Inhalation characteristics of asthma patients, COPD patients and healthy volunteers with the Spiromax® and Turbuhaler® devices: a randomised, cross-over study.

BACKGROUND: Spiromax® is a novel dry-powder inhaler containing formulations of budesonide plus formoterol (BF). The device is intended to provide dose equivalence with enhanced user-friendliness compared to BF Turbuhaler® in asthma and chronic obstructive pulmonary disease (COPD). The present study was performed to compare inhalation parameters with empty versions of the two devices, and to investigate the effects of enhanced training designed to encourage faster inhalation. METHODS: This randomised, open-label, cross-over study included children with asthma (n = 23), adolescents with asthma (n = 27), adults with asthma (n = 50), adults with COPD (n = 50) and healthy adult volunteers (n = 50). Inhalation manoeuvres were recorded with each device after training with the patient information leaflet (PIL) and after enhanced training using an In-Check Dial device. RESULTS: After PIL training, peak inspiratory flow (PIF), maximum change in pressure (∆P) and the inhalation volume (IV) were significantly higher with Spiromax than with the Turbuhaler device (p values were at least <0.05 in all patient groups). After enhanced training, numerically or significantly higher values for PIF, ∆P, IV and acceleration remained with Spiromax versus Turbuhaler, except for ∆P in COPD patients. After PIL training, one adult asthma patient and one COPD patient inhaled <30 L/min through the Spiromax compared to one adult asthma patient and five COPD patients with the Turbuhaler. All patients achieved PIF values of at least 30 L/min after enhanced training. CONCLUSIONS: The two inhalers have similar resistance so inhalation flows and pressure changes would be expected to be similar. The higher flow-related values noted for Spiromax versus Turbuhaler after PIL training suggest that Spiromax might have human factor advantages in real-world use. After enhanced training, the flow-related differences between devices persisted; increased flow rates were achieved with both devices, and all patients achieved the minimal flow required for adequate drug delivery. Enhanced training could be useful, especially in COPD patients

Vacuum stability, neutrinos, and dark matter

Motivated by the discovery hint of the Standard Model (SM) Higgs mass around 125 GeV at the LHC, we study the vacuum stability and perturbativity bounds on Higgs scalar of the SM extensions including neutrinos and dark matter (DM). Guided by the SM gauge symmetry and the minimal changes in the SM Higgs potential we consider two extensions of neutrino sector (Type-I and Type-III seesaw mechanisms) and DM sector (a real scalar singlet (darkon) and minimal dark matter (MDM)) respectively. The darkon contributes positively to the $\beta$ function of the Higgs quartic coupling $\lambda$ and can stabilize the SM vacuum up to high scale. Similar to the top quark in the SM we find the cause of instability is sensitive to the size of new Yukawa couplings between heavy neutrinos and Higgs boson, namely, the scale of seesaw mechanism. MDM and Type-III seesaw fermion triplet, two nontrivial representations of $SU(2)_{L}$ group, will bring the additional positive contributions to the gauge coupling $g_{2}$ renormalization group (RG) evolution and would also help to stabilize the electroweak vacuum up to high scale.Comment: 18 pages, 15 figures; published versio

Chemotaxis When Bacteria Remember: Drift versus Diffusion

{\sl Escherichia coli} ({\sl E. coli}) bacteria govern their trajectories by switching between running and tumbling modes as a function of the nutrient concentration they experienced in the past. At short time one observes a drift of the bacterial population, while at long time one observes accumulation in high-nutrient regions. Recent work has viewed chemotaxis as a compromise between drift toward favorable regions and accumulation in favorable regions. A number of earlier studies assume that a bacterium resets its memory at tumbles -- a fact not borne out by experiment -- and make use of approximate coarse-grained descriptions. Here, we revisit the problem of chemotaxis without resorting to any memory resets. We find that when bacteria respond to the environment in a non-adaptive manner, chemotaxis is generally dominated by diffusion, whereas when bacteria respond in an adaptive manner, chemotaxis is dominated by a bias in the motion. In the adaptive case, favorable drift occurs together with favorable accumulation. We derive our results from detailed simulations and a variety of analytical arguments. In particular, we introduce a new coarse-grained description of chemotaxis as biased diffusion, and we discuss the way it departs from older coarse-grained descriptions.Comment: Revised version, journal reference adde

Implementation of routine outcome measurement in child and adolescent mental health services in the United Kingdom: a critical perspective

The aim of this commentary is to provide an overview of clinical outcome measures that are currently recommended for use in UK Child and Adolescent Mental Health Services (CAMHS), focusing on measures that are applicable across a wide range of conditions with established validity and reliability, or innovative in their design. We also provide an overview of the barriers and drivers to the use of Routine Outcome Measurement (ROM) in clinical practice

Integrating evolution into ecological modelling: accommodating phenotypic changes in agent based models.

PMCID: PMC3733718This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Evolutionary change is a characteristic of living organisms and forms one of the ways in which species adapt to changed conditions. However, most ecological models do not incorporate this ubiquitous phenomenon. We have developed a model that takes a 'phenotypic gambit' approach and focuses on changes in the frequency of phenotypes (which differ in timing of breeding and fecundity) within a population, using, as an example, seasonal breeding. Fitness per phenotype calculated as the individual's contribution to population growth on an annual basis coincide with the population dynamics per phenotype. Simplified model variants were explored to examine whether the complexity included in the model is justified. Outputs from the spatially implicit model underestimated the number of individuals across all phenotypes. When no phenotype transitions are included (i.e. offspring always inherit their parent's phenotype) numbers of all individuals are always underestimated. We conclude that by using a phenotypic gambit approach evolutionary dynamics can be incorporated into individual based models, and that all that is required is an understanding of the probability of offspring inheriting the parental phenotype

Successful new product development by optimizing development process effectiveness in highly regulated sectors: the case of the Spanish medical devices sector

Rapid development and commercialization of new products is of vital importance for small and medium sized enterprises (SME) in regulated sectors. Due to strict regulations, competitive advantage can hardly be achieved through the effectiveness of product concepts only. If an SME in a highly regulated sector wants to excell in new product development (NPD) performance, the company should focus on the flexibility, speed, and productivity of its NPD function: i.e. the development process effectiveness. Our main research goals are first to explore if SMEs should focus on their their development process effectiveness rather than on their product concept effectiveness to achieve high NPD performance; and second, to explore whether a shared pattern in the organization of the NPD function can be recognized to affect NPD performance positively. The medical devices sector in Spain is used as an example of a\ud highly regulated sector. A structured survey among 11 SMEs, of which 2 were studied also as in in-depth case studies, led to the following results. First of all, indeed the companies in the dataset which focused on the effectiveness of their development process, stood out in NPD performance. Further, the higher performing companies did have a number of commonalities in the organisation of their NPD function: 1) The majority of the higher performing firms had an NPD strategy characterized by a predominantly incremental project portfolio.\ud 2) a) Successful firms with an incremental project portfolio combined this with a functional team structure b) Successful firms with a radical project portfolio combined this with a heavyweight or autonomous team structure.\ud 3) A negative reciprocal relationship exists between formalization of the NPD processes and the climate of the NPD function, in that a formalized NPD process and an innovative climate do not seem to reinforce each other. Innovative climate combined with an informal NPD process does however contribute positively to NPD performance. This effect was stronger in combination with a radical project portfolio. The highest NPD performance was measured for companies focusing mainly on incremental innovation. It is argued that in highly regulated sectors, companies with an incremental product portfolio would benefit from employing a functional structure. Those companies who choose for a more radical project portfolio in highly regulated sectors should be aware\ud that they are likely to excell only in the longer term by focusing on strategic flexibility. In their NPD organization, they might be well advised to combine informal innovation processes with an innovative climate

One size does not fit all - stroke survivor's views on group self-management interventions

INTRODUCTION: Stroke is the main cause of complex disability in the UK. Many stroke survivors feel abandoned when rehabilitation ends and more than half are left with long-term unmet needs. There is now emerging interest in whether group self-management programs (SMP) specifically for stroke survivors could help. However, more work is required to understand the acceptability of group SMPs to stroke survivors and the factors of concern that could impact efficacy. PURPOSE: The purpose of this study is to explore stroke survivor's views on (1) possible benefits of a group SMP, (2) possible challenges of a group SMP, and (3) when/where to implement a SMP in an individual's stroke journey. METHOD: Fourteen stroke survivors took part in semi-structured interviews, which were analyzed using an inductive thematic approach. RESULTS: Three main themes were identified in the data: (1) a space to share support, (2) it is not a one size fits all problem, and (3) how is it all going to happen? CONCLUSION: A varied group of stroke survivors can provide valuable insight and ideas about how group SMP's should be constructed. To the best of our knowledge, this is the first patient engagement study that explores group SMPs for stroke. In future work, researchers may find it helpful to consider the findings from this study to inform the design of group SMPs. Implications for Rehabilitation There is interest in whether unmet needs after stroke could be addressed through a group self-management program (SMP). Stroke survivors can provide valuable insight and ideas about how group SMPs should be constructed. Group SMPs should carefully consider: how to create a safe space in which stroke survivors feel comfortable, the impact of the facilitators, tailoring the group to the individual, the presence of carers, and the emotional impact of a group SMP

Flavor Violating Higgs Decays

We study a class of nonstandard interactions of the newly discovered 125 GeV Higgs-like resonance that are especially interesting probes of new physics: flavor violating Higgs couplings to leptons and quarks. These interaction can arise in many frameworks of new physics at the electroweak scale such as two Higgs doublet models, extra dimensions, or models of compositeness. We rederive constraints on flavor violating Higgs couplings using data on rare decays, electric and magnetic dipole moments, and meson oscillations. We confirm that flavor violating Higgs boson decays to leptons can be sizeable with, e.g., h -> tau mu and h -> tau e branching ratios of order 10% perfectly allowed by low energy constraints. We estimate the current LHC limits on h -> tau mu and h -> tau e decays by recasting existing searches for the SM Higgs in the tau-tau channel and find that these bounds are already stronger than those from rare tau decays. We also show that these limits can be improved significantly with dedicated searches and we outline a possible search strategy. Flavor violating Higgs decays therefore present an opportunity for discovery of new physics which in some cases may be easier to access experimentally than flavor conserving deviations from the Standard Model Higgs framework.Comment: 39 pages, 12 figures, 3 tables; v2: Improved referencing, updated mu -> 3e bounds to include large loop contributions, corrected single top constraints; conclusions unchanged; matches version to be published in JHEP; v3: included 2-loop contributions in mu -> e conversion, improved discussion of tau -> 3 mu and of EDM constraints on FV top-Higgs couplings; conclusions unchange

The influence of the atmospheric boundary layer on nocturnal layers of noctuids and other moths migrating over southern Britain

Insects migrating at high altitude over southern Britain have been continuously monitored by automatically-operating, vertical-looking radars over a period of several years. During some occasions in the summer months, the migrants were observed to form well-defined layer concentrations, typically at heights of 200-400 m, in the stable night-time atmosphere. Under these conditions, insects are likely to have control over their vertical movements and are selecting flight heights which are favourable for long-range migration. We therefore investigated the factors influencing the formation of these insect layers by comparing radar measurements of the vertical distribution of insect density with meteorological profiles generated by the UK Met. Office’s Unified Model (UM). Radar-derived measurements of mass and displacement speed, along with data from Rothamsted Insect Survey light traps provided information on the identity of the migrants. We present here three case studies where noctuid and pyralid moths contributed substantially to the observed layers. The major meteorological factors influencing the layer concentrations appeared to be: (a) the altitude of the warmest air, (b) heights corresponding to temperature preferences or thresholds for sustained migration and (c), on nights when air temperatures are relatively high, wind-speed maxima associated with the nocturnal jet. Back-trajectories indicated that layer duration may have been determined by the distance to the coast. Overall, the unique combination of meteorological data from the UM and insect data from entomological radar described here show considerable promise for systematic studies of high-altitude insect layering

The effectiveness of constraint-led training on skill development in interceptive sports: a systematic review (Clark, McEwan and Christie) – a commentary

Clark, McEwan and Christie's systematic review1 offers a timely examination of current literature assessing effects of a constraints-led approach (CLA) to training on ‘technical and cognitive skill in sport’, in comparison to traditional training methods. They concluded that, currently, there is strong evidence to advocate for the effects of training interventions that espouse benefits of constraints-led training on acquiring skill in interceptive actions. Clark, McEwan and Christie reported that 18 studies satisfied their proposed inclusion criteria and, of these studies, 77% provided evidence of the effectiveness of the CLA. Consequently, Clark, McEwan and Christie argued that a ‘the implementation of the constraints-led approach within interceptive sport can be advocated’ (p. 17). This is a revealing insight, which supports their claims that this finding ‘provides the opportunity for researchers to collect more compelling evidence to answer the question: “Does constraint-led training assist with the development of technical skills within interceptive sport?”’. While we endorse their call for more empirical evidence on the effectiveness of a CLA to practice and training design, we qualify it by highlighting some limitations of Clark, McEwan and Christie's systematic review