'Help for hay fever', a goal-focused intervention for people with intermittent allergic rhinitis, delivered in Scottish community pharmacies: study protocol for a pilot cluster randomized controlled trial

<b>Background</b> Despite the availability of evidence-based guidelines for managing allergic rhinitis in primary care, management of the condition in the United Kingdom (UK) remains sub-optimal. Its high prevalence and negative effects on quality of life, school performance, productivity and co-morbid respiratory conditions (in particular, asthma), and high health and societal costs, make this a priority for developing novel models of care. Recent Australian research demonstrated the potential of a community pharmacy-based ‘goal-focused’ intervention to help people with intermittent allergic rhinitis to self-manage their condition better, reduce symptom severity and improve quality of life. In this pilot study we will assess the transferability of the goal-focused intervention to a UK context, the suitability of the intervention materials, procedures and outcome measures and collect data to inform a future definitive UK randomized controlled trial (RCT). <p></p> <b>Methods/design</b> A pilot cluster RCT with associated preliminary economic analysis and embedded qualitative evaluation. The pilot trial will take place in two Scottish Health Board areas: Grampian and Greater Glasgow and Clyde. Twelve community pharmacies will be randomly assigned to intervention or usual care group. Each will recruit 12 customers seeking advice or treatment for intermittent allergic rhinitis. Pharmacy staff in intervention pharmacies will support recruited customers in developing strategies for setting and achieving goals that aim to avoid/minimize triggers for, and eliminate/minimize symptoms of allergic rhinitis. Customers recruited in non-intervention pharmacies will receive usual care. The co-primary outcome measures, selected to inform a sample size calculation for a future RCT, are: community pharmacy and customer recruitment and completion rates; and effect size of change in the validated mini-Rhinoconjunctivitis Quality of Life Questionnaire between baseline, one-week and six-weeks post-intervention. Secondary outcome measures relate to changes in symptom severity, productivity, medication adherence and self-efficacy. Quantitative data about accrual, retention and economic measures, and qualitative data about participants’ experiences during the trial will be collected to inform the future RCT.<P></P> <b>Discussion</b> This work will lay the foundations for a definitive RCT of a community pharmacy-based ‘goal-focused’ self-management intervention for people with intermittent allergic rhinitis. Results of the pilot trial are expected to be available in April 2013

Gamma-ray bursts and terrestrial planetary atmospheres

We describe results of modeling the effects on Earth-like planets of long-duration gamma-ray bursts (GRBs) within a few kiloparsecs. A primary effect is generation of nitrogen oxide compounds which deplete ozone. Ozone depletion leads to an increase in solar UVB radiation at the surface, enhancing DNA damage, particularly in marine microorganisms such as phytoplankton. In addition, we expect increased atmospheric opacity due to buildup of nitrogen dioxide produced by the burst and enhanced precipitation of nitric acid. We review here previous work on this subject and discuss recent developments, including further discussion of our estimates of the rates of impacting GRBs and the possible role of short-duration bursts.Comment: 12 pages including 5 figures (4 in color). Added discussion of GRB rates and biological effects. Accepted for publication in New Journal of Physics, for special issue "Focus on Gamma-Ray Bursts

Syntaxin 16 and syntaxin 5 are required for efficient retrograde transport of several exogenous and endogenous cargo proteins

Retrograde transport allows proteins and lipids to leave the endocytic pathway to reach other intracellular compartments, such as trans-Golgi network (TGN)/Golgi membranes, the endoplasmic reticulum and, in some instances, the cytosol. Here, we have used RNA interference against the SNARE proteins syntaxin 5 and syntaxin 16, combined with recently developed quantitative trafficking assays, morphological approaches and cell intoxication analysis to show that these SNARE proteins are not only required for efficient retrograde transport of Shiga toxin, but also for that of an endogenous cargo protein - the mannose 6-phosphate receptor - and for the productive trafficking into cells of cholera toxin and ricin. We have found that the function of syntaxin 16 was specifically required for, and restricted to, the retrograde pathway. Strikingly, syntaxin 5 RNA interference protected cells particularly strongly against Shiga toxin. Since our trafficking analysis showed that apart from inhibiting retrograde endosome-to-TGN transport, the silencing of syntaxin 5 had no additional effect on Shiga toxin endocytosis or trafficking from TGN/Golgi membranes to the endoplasmic reticulum, we hypothesize that syntaxin 5 also has trafficking-independent functions. In summary, our data demonstrate that several cellular and exogenous cargo proteins use elements of the same SNARE machinery for efficient retrograde transport between early/recycling endosomes and TGN/Golgi membranes

Truly unentangled photon pairs without spectral filtering

We demonstrate that an integrated silicon microring resonator is capable of efficiently producing photon pairs that are completely unentangled; such pairs are a key component of heralded single photon sources. A dual-channel interferometric coupling scheme can be used to independently tune the quality factors associated with the pump and signal and idler modes, yielding a biphoton wavefunction with Schmidt number arbitrarily close to unity. This will permit the generation of heralded single photon states with unit purity.Comment: 5 pages, 3 figure

EXCEDE Technology Development III: First Vacuum Tests

This paper is the third in the series on the technology development for the EXCEDE (EXoplanetary Circumstellar Environments and Disk Explorer) mission concept, which in 2011 was selected by NASA's Explorer program for technology development (Category III). EXCEDE is a 0.7m space telescope concept designed to achieve raw contrasts of 1e6 at an inner working angle of 1.2 l/D and 1e7 at 2 l/D and beyond. This will allow it to directly detect and spatially resolve low surface brightness circumstellar debris disks as well as image giant planets as close as in the habitable zones of their host stars. In addition to doing fundamental science on debris disks, EXCEDE will also serve as a technological and scientific precursor for any future exo-Earth imaging mission. EXCEDE uses a Starlight Suppression System (SSS) based on the PIAA coronagraph, enabling aggressive performance. We report on our continuing progress of developing the SSS for EXCEDE, and in particular (a) the reconfiguration of our system into a more flight-like layout, with an upstream deformable mirror and an inverse PIAA system, as well as a LOWFS, and (b) testing this system in a vacuum chamber, including IWA, contrast, and stability performance. The results achieved so far are 2.9e-7 contrast between 1.2-2.0 l/D and 9.7e-8 contrast between 2.0-6.0 l/D in monochromatic light; as well as 1.4e-6 between 2.0-6.0 l/D in a 10% band, all with a PIAA coronagraph operating at an inner working angle of 1.2 l/D. This constitutes better contrast than EXCEDE requirements (in those regions) in monochromatic light, and progress towards requirements in broadband light. Even though this technology development is primarily targeted towards EXCEDE, it is also germane to any exoplanet direct imaging space-based telescopes because of the many challenges common to different coronagraph architectures and mission requirements.Comment: 12 pages, 12 figures, to be published in proceedings of SPIE Astronomical Telescopes + Instrumentation (2014

Releasing The Anti-inflammatory Potential of Paralysed Skeletal Muscle: The Circulating Cytokine Response to Voluntary Upper-limb Exercise With/Without The Addition of Functional Electrical Stimulation (FES)-evoked Lower-limb Contractions

Skeletal muscle is a rich store of inflammatory mediating ‘myokines’. Following release from contracting muscle, the myokine interleukin-6 (IL-6) promotes a circulating anti-inflammatory environment associated with a reduced risk of cardiovascular disease (CVD). The metabolic and functional consequences of lower-limb paralysis, including the gain in relative adiposity and physical inactivity, result in a high prevalence of CVD in individuals with a spinal cord injury (SCI). However, the magnitude of any contraction-induced myokine response in this population may be limited by the small active muscle mass of the upper-limb. The combination of voluntary, upper-limb exercise and involuntary, functional electrical stimulation (FES)-evoked lower-limb cycling termed ‘hybrid’ exercise, may augment the acute myokine response by activating a greater volume of muscle mass than upper-limb exercise alone. Five community-based individuals with motor complete, thoracic SCI (Age=44±15 years; Body mass=66.6±14.3 kg) and at least 3 months FES-evoked cycling experience volunteered to participate. On separate occasions, each participant performed 30 min of voluntary upper-limb, hand cycling exercise with (HYBRID) and without (ARM only) the addition of FES-evoked lower-limb cycling at a fixed workload. Blood samples were collected at rest, immediately post-exercise, and 1 and 2 h post-exercise. Plasma concentrations of IL-6, IL-10 and IL-1ra were subsequently determined by enzyme linked immunoassay. Estimated energy expenditure was significantly higher in HYBRID (154±25 kcal) than ARM (132±21 kcal) (P=0.01; ES=0.90). Plasma IL-6 concentrations were significantly elevated following HYBRID, with values 1 h and 2 h post-exercise significantly higher than rest and immediately post-exercise (P\u3c0.04). A small (~50%) non-significant increase in IL-6 was present 1 h and 2 h post-exercise following ARM, however concentrations were significantly higher in HYBRID than ARM at the same time points (P\u3c0.02). Plasma IL-10 concentrations were unaffected by exercise in ARM. Although not attaining statistical significance, there was a tendency for IL-10 concentrations to rise in HYBRID, with an 85% increase in IL-10 concentrations at 2 h post exercise. Plasma IL-1ra was unaffected by exercise in both trials. Initial findings suggest paralysed skeletal muscle releases the myokine IL-6 in response to electrically evoked contractions. Further, voluntary upper-limb exercise combined with involuntary lower-limb FES-evoked exercise had the tendency to elevate plasma concentrations of the anti-inflammatory cytokine IL-10; this effect was not present when performing arm exercise alone. Hybrid exercise may offer a method of maximising the anti-inflammatory potential of acute exercise in individuals with a SCI. The current findings require verification in a larger cohort