Single maintenance and reliever therapy (SMART) of asthma: a critical appraisal

The use of a combination inhaler containing budesonide and formoterol as both maintenance and quick relief therapy (SMART) has been recommended as an improved method of using inhaled corticosteroid/long-acting β agonist (ICS/LABA) therapy. Published double-blind trials show that budesonide/formoterol therapy delivered in SMART fashion achieves better asthma outcomes than budesonide monotherapy or lower doses of budesonide/formoterol therapy delivered in constant dosage. Attempts to compare budesonide/formoterol SMART therapy with regular combination ICS/LABA dosing using other compounds have been confounded by a lack of blinding and unspecified dose adjustment strategies. The asthma control outcomes in SMART-treated patients are poor; it has been reported that only 17.1% of SMART-treated patients are controlled. In seven trials of 6–12 months duration, patients using SMART have used quick reliever daily (weighted average 0.92 inhalations/day), have awakened with asthma symptoms once every 7–10 days (weighted average 11.5% of nights), have suffered asthma symptoms more than half of days (weighted average 54.0% of days) and have had a severe exacerbation rate of one in five patients per year (weighted average 0.22 severe exacerbations/patient/year). These poor outcomes may reflect the recruitment of a skewed patient population. Although improvement from baseline has been attributed to these patients receiving additional ICS therapy at pivotal times, electronic monitoring has not been used to test this hypothesis nor the equally plausible hypothesis that patients who are non-compliant with maintenance medication have used budesonide/formoterol as needed for self-treatment of exacerbations. Although the long-term consequences of SMART therapy have not been studied, its use over 1 year has been associated with significant increases in sputum and biopsy eosinophilia. At present, there is no evidence that better asthma treatment outcomes can be obtained by moment-to-moment symptom-driven use of ICS/LABA therapy than conventional physician-monitored and adjusted ICS/LABA therapy

Cell wall glycans and soluble factors determine the interactions between the hyphae of Candida albicans and Pseudomonas aeruginosa

The fungus, Candida albicans, and the bacterium, Pseudomonas aeruginosa, are opportunistic human pathogens that have been coisolated from diverse body sites. Pseudomonas aeruginosa suppresses C. albicans proliferation in vitro and potentially in vivo but it is the C. albicans hyphae that are killed while yeast cells are not. We show that hyphal killing involves both contact-mediated and soluble factors. Bacterial culture filtrates contained heat-labile soluble factors that killed C. albicans hyphae. In cocultures, localized points of hyphal lysis were observed, suggesting that adhesion and subsequent bacteria-mediated cell wall lysis is involved in the killing of C. albicans hyphae. The glycosylation status of the C. albicans cell wall affected the rate of contact-dependent killing because mutants with severely truncated O-linked, but not N-linked, glycans were hypersensitive to Pseudomonas-mediated killing. Deletion of HWP1, ALS3 or HYR1, which encode major hypha-associated cell wall proteins, had no effect on fungal susceptibility

Interdye Hole Transport Accelerates Recombination in Dye Sensitized Mesoporous Films

Charge recombination between oxidized dyes attached to mesoporous TiO2 and electrons in the TiO2 was studied in inert electrolytes using transient absorption spectroscopy. Simultaneously, hole transport within the dye monolayers was monitored by transient absorption anisotropy. The rate of recombination decreased when hole transport was inhibited selectively, either by decreasing the dye surface coverage or by changing the electrolyte environment. From Monte Carlo simulations of electron and hole diffusion in a particle, modeled as a cubic structure, we identify the conditions under which hole lifetime depends on the hole diffusion coefficient for the case of normal (disorder free) diffusion. From simulations of transient absorption and transient absorption anisotropy, we find that the rate and the dispersive character of hole transport in the dye monolayer observed spectroscopically can be explained by incomplete coverage and disorder in the monolayer. We show that dispersive transport in the dye monolayer combined with inhomogeneity in the TiO2 surface reactivity can contribute to the observed stretched electron-hole recombination dynamics and electron density dependence of hole lifetimes. Our experimental and computational analysis of lateral processes at interfaces can be applied to investigate and optimize charge transport and recombination in solar energy conversion devices using electrodes functionalized with molecular light absorbers and catalysts

Internal Structure of a Glacier on Mars Revealed by Gully Incision

International audienceDebris transport from / A Mars glacier bed to / Flowlines on surface

The journey effect: how travel affects the experiences of mental health in-patient service-users and their families

The qualitative study presented in this paper explored the perspectives of service-users, family members and staff about the impact of travel issues on the lives of mental health in-patients and carers. This topic was chosen because it was prioritised by members of Xplore, a service-user and carer research group, and has received little research attention. Travel problems were a significant issue for many service-users and carers, bound-up with mental health issues and the recovery experience. Travel facilitation through the funding of taxis and the provision of guides was appreciated. A few service-users and carers positively valued distancing from their previous home environment. The meaning of travel issues could only be understood in the context of individuals’ wider lives and relationships. The significance of the findings is discussed in relation to the social model of disability

Inter-laboratory Characterisation of Apatite Reference Materials for Chlorine Isotope Analysis

Here we report on a set of six apatite reference materials (chlorapatites MGMH#133648, TUBAF#38 and fluorapatites MGMH#128441A, TUBAF#37, 40, 50) which we have characterised for their chlorine isotope ratios; these RMs span a range of Cl mass fractions within the apatite Ca-10(PO4)(6)(F,Cl,OH)(2) solid solution series. Numerous apatite specimens, obtained from mineralogical collections, were initially screened for Cl-37/Cl-35 homogeneity using SIMS followed by delta Cl-37 characterisation by gas source mass spectrometry using both dual-inlet and continuous-flow modes. We also report major and key trace element compositions as determined by EPMA. The repeatability of our SIMS results was better than +/- 0.10% (1s) for the five samples with > 0.5% m/m Cl and +/- 0.19% (1s) for the low Cl abundance material (0.27% m/m). We also observed a small, but significant crystal orientation effect of 0.38% between the mean Cl-37/Cl-35 ratios measured on three oriented apatite fragments. Furthermore, the results of GS-IRMS analyses show small but systematic offset of delta Cl-37(SMOC) values between the three laboratories. Nonetheless, all studied samples have comparable chlorine isotope compositions, with mean 10(3)delta Cl-37(SMOC) values between +0.09 and +0.42 and in all cases with 1s <= +/- 0.25

Perpendicular local magnetization under voltage control in Ni films on ferroelectric BaTiO₃ substrates.

High-resolution magnetoelectric imaging is used to demonstrate electrical control of the perpendicular local magnetization associated with 125 nm-wide magnetic stripe domains in 100-nm-thick Ni films. This magnetoelectric coupling is achieved in zero magnetic field using strain from ferroelectric BaTiO3 substrates to control perpendicular anisotropy imposed by the growth stress. These findings may be exploited for perpendicular recording in nanopatterned hybrid media.This work was funded by Isaac Newton Trust grants 10.26(u) and 11.35 (u), UK EPSRC grant EP/G031509/1, a Herchel Smith Fellowship (X.M.), the Spanish MEC Ramón y Cajal programme (X.M.), and the Royal Society (X.M.). The authors thank Luis Hueso and Raffaele Pellicelli for discussions.This is the final published version. It first appeared at http://onlinelibrary.wiley.com/doi/10.1002/adma.201404799/abstract

Predicting invasive fungal disease due to Candida species in non-neutropenic, critically ill, adult patients in United Kingdom critical care units.

BACKGROUND: Given the predominance of invasive fungal disease (IFD) amongst the non-immunocompromised adult critically ill population, the potential benefit of antifungal prophylaxis and the lack of generalisable tools to identify high risk patients, the aim of the current study was to describe the epidemiology of IFD in UK critical care units, and to develop and validate a clinical risk prediction tool to identify non-neutropenic, critically ill adult patients at high risk of IFD who would benefit from antifungal prophylaxis. METHODS: Data on risk factors for, and outcomes from, IFD were collected for consecutive admissions to adult, general critical care units in the UK participating in the Fungal Infection Risk Evaluation (FIRE) Study. Three risk prediction models were developed to model the risk of subsequent Candida IFD based on information available at three time points: admission to the critical care unit, at the end of 24 h and at the end of calendar day 3 of the critical care unit stay. The final model at each time point was evaluated in the three external validation samples. RESULTS: Between July 2009 and April 2011, 60,778 admissions from 96 critical care units were recruited. In total, 359 admissions (0.6 %) were admitted with, or developed, Candida IFD (66 % Candida albicans). At the rate of candidaemia of 3.3 per 1000 admissions, blood was the most common Candida IFD infection site. Of the initial 46 potential variables, the final admission model and the 24-h model both contained seven variables while the end of calendar day 3 model contained five variables. The end of calendar day 3 model performed the best with a c index of 0.709 in the full validation sample. CONCLUSIONS: Incidence of Candida IFD in UK critical care units in this study was consistent with reports from other European epidemiological studies, but lower than that suggested by previous hospital-wide surveillance in the UK during the 1990s. Risk modeling using classical statistical methods produced relatively simple risk models, and associated clinical decision rules, that provided acceptable discrimination for identifying patients at 'high risk' of Candida IFD. TRIAL REGISTRATION: The FIRE Study was reviewed and approved by the Bolton NHS Research Ethics Committee (reference: 08/H1009/85), the Scotland A Research Ethics Committee (reference: 09/MRE00/76) and the National Information Governance Board (approval number: PIAG 2-10(f)/2005)

Planetary Construction Zones in Occultation: Discovery of an Extrasolar Ring System Transiting a Young Sun-like Star and Future Prospects for Detecting Eclipses by Circumsecondary and Circumplanetary Disks

The large relative sizes of circumstellar and circumplanetary disks imply that they might be seen in eclipse in stellar light curves. We estimate that a survey of ~10^4 young (~10 Myr old) post-accretion pre-MS stars monitored for ~10 years should yield at least a few deep eclipses from circumplanetary disks and disks surrounding low mass companion stars. We present photometric and spectroscopic data for a pre-MS K5 star (1SWASP J140747.93-394542.6), a newly discovered ~0.9 Msun member of the ~16 Myr-old Upper Cen-Lup subgroup of Sco-Cen at a kinematic distance of 128 pc. SuperWASP and ASAS light curves for this star show a remarkably long, deep, and complex eclipse event centered on 29 April 2007. At least 5 multi-day dimming events of >0.5 mag are identified, with a >3.3 mag deep eclipse bracketed by two pairs of ~1 mag eclipses symmetrically occurring +-12 days and +-26 days before and after. Hence, significant dimming of the star was taking place on and off over at least a ~54 day period in 2007, and a strong >1 mag dimming event occurred over a ~12 day span. We place a firm lower limit on the period of 850 days (i.e. the orbital radius of the eclipser must be >1.7 AU and orbital velocity must be <22 km/s). The shape of the light curve is similar to the lop-sided eclipses of the Be star EE Cep. We suspect that this new star is being eclipsed by a low-mass object orbited by a dense inner disk, girded by at least 3 dusty rings of lower optical depth. Between these rings are at least two annuli of near-zero optical depth (i.e. gaps), possibly cleared out by planets or moons, depending on the nature of the secondary. For possible periods in the range 2.33-200 yr, the estimated total ring mass is ~8-0.4 Mmoon (if the rings have optical opacity similar to Saturn's rings), and the edge of the outermost detected ring has orbital radius ~0.4-0.09 AU.Comment: Astronomical Journal, in press, 13 figure