Sustained release microparticles for pulmonary drug delivery.

In this study, several formulation approaches for generating sustained release (SR) microparticles suitable for pulmonary deposition are described. The model drug chosen for investigation was the hydrophilic β2-adrenoceptor agonist, Terbutaline Sulphate (TS), used in the treatment of asthma. A particular challenge to achieving suitable sustained release profiles arose from the high water solubility and ionised state of TS. Initial investigations focused on generating TS microcrystals, which would be subsequently coated with a SR excipient. A controlled crystallization method was developed in which TS was crystallized from an anti-solvent, which contained particle size restricting growth retardants. Significantly smaller crystals were obtained in the presence of growth retardants relative to crystallization without retardants. However, the smallest crystals obtained (3.6 μm) were too large for progression, as the application of a SR coat to such crystals would have increased particle size beyond that suitable for inhalation. The next investigation assessed TS release from a polysaccharide matrix particle containing molecularly dispersed active. Drug release was measured (HPLC) using a custom-built diffusion cell, designed to mimic release at the pulmonary epithelium. Release profiles showed that a degree of SR was possible from polysaccharide-based particles; although, SR was not sufficient for further development. Finally TS nanoparticles, obtained from an emulsion-template process, were encapsulated (spray-drying) within hydrophobic microparticles of respirable particle size. Several optimised formulations of this type provided promising in-vitro sustained release of the active at a variety of drug loadings and in a range of release media. The most useful SR excipient chosen for further development was hydrogenated palm oil, which was observed to coat the nanoparticles effectively. In-vitro deposition profiles were determined for a selection of formulations using an Andersen Cascade Impactor, and it was shown that deposition profiles were formulation-dependant and of size ranges suitable for pulmonary deposition

The estimated prevalence and incidence of late stage age related macular degeneration in the UK

BACKGROUND: UK estimates of age related macular degeneration (AMD) occurrence vary. AIMS: To estimate prevalence, number and incidence of AMD by type in the UK population aged ≥50 years. METHODS: Age-specific prevalence rates of AMD obtained from a Bayesian meta-analysis of AMD prevalence were applied to UK 2007-2009 population data. Incidence was estimated from modelled age-specific prevalence. RESULTS: Overall prevalence of late AMD was 2.4% (95% credible interval (CrI) 1.7% to 3.3%), equivalent to 513 000 cases (95% CrI 363 000 to 699 000); estimated to increase to 679 000 cases by 2020. Prevalences were 4.8% aged ≥65 years, 12.2% aged ≥80 years. Geographical atrophy (GA) prevalence rates were 1.3% (95% CrI 0.9% to 1.9%), 2.6% (95% CrI 1.8% to 3.7%) and 6.7% (95% CrI 4.6% to 9.6%); neovascular AMD (NVAMD) 1.2% (95% CrI 0.9% to 1.7%), 2.5% (95% CrI 1.8% to 3.4%) and 6.3% (95% CrI 4.5% to 8.6%), respectively. The estimated number of prevalent cases of late AMD were 60% higher in women versus men (314 000 cases in women, 192 000 men). Annual incidence of late AMD, GA and NVAMD per 1000 women was 4.1 (95% CrI 2.4% to 6.8%), 2.4 (95% CrI 1.5% to 3.9%) and 2.3 (95% CrI 1.4% to 4.0%); in men 2.6 (95% CrI 1.5% to 4.4%), 1.7 (95% CrI 1.0% to 2.8%) and 1.4 (95% CrI 0.8% to 2.4%), respectively. 71 000 new cases of late AMD were estimated per year. CONCLUSIONS: These estimates will guide health and social service provision for those with late AMD and enable estimation of the cost of introducing new treatments

The use of a long-acting tranquilizer (zuclopenthixol acetate) and live video monitoring for successful long-distance transport of caribou (Rangifer tarandus)

Long-distance transport of caribou (Rangifer tarandus) can result in morbidities and mortalities. This case report describes the use of a long-acting tranquilizer, zuclopenthixol acetate (ZA) and live video monitoring (LVM) to transport caribou over 2300 kilometers. Two groups of captive caribou were transported from Fort St. John, British Columbia to Dryden, Ontario (n=14; 28.5 h transport) and Anchorage, Alaska (n=11; 32 h transport).  The day prior to transport, caribou were administered ZA at 1 mg/kg via deep intramuscular (IM) injection.  Digital video cameras allowed for live observation of caribou during transport.  Still images of videos from each compartment in the Ontario transport were analyzed for percentage (%) lying versus standing over three time periods (Day 1, Night, and Day 2).  Overall, caribou spent 57% of the transport lying down, with the highest percentage occurring at night (73%).  As group size and animal density decreased there was a trend for caribou to spend more time lying down.  Three animals developed extrapyramidal effects to the ZA and were effectively treated with midazolam at 0.2 mg/kg IM. There were no significant visible injuries or mortalities during or up to 6 weeks post-transport. Zuclopenthixol acetate and LVM were used to successfully transport  caribou over long distances and should be considered in future translocations to improve animal welfare during transport.  

Travel to School and Physical Activity Levels in 9-10 Year-Old UK Children of Different Ethnic Origin; Child Heart and Health Study in England (CHASE)

BACKGROUND: Travel to school may offer a convenient way to increase physical activity levels in childhood. We examined the association between method of travel to school and physical activity levels in urban multi-ethnic children. METHODS AND FINDINGS: 2035 children (aged 9-10 years in 2006-7) provided data on their usual method of travel to school and wore an Actigraph-GT1M activity monitor during waking hours. Associations between method of travel and mean level of physical activity (counts per minute [CPM], steps, time spent in light, moderate or vigorous activity per day) were examined in models adjusted for confounding variables. 1393 children (69%) walked or cycled to school; 161 (8%) used public transport and 481 (24%) travelled by car. White European children were more likely to walk/cycle, black African Caribbeans to travel by public transport and South Asian children to travel by car. Children travelling by car spent less time in moderate to vigorous physical activity (-7 mins, 95%CI-9,-5), and had lower CPM (-32 CPM, 95%CI-44,-19) and steps per day (-813 steps, 95%CI,-1043,-582) than walkers/cyclists. Pupils travelling by public transport had similar activity levels to walkers/cyclists. Lower physical activity levels amongst car travellers' were especially marked at travelling times (school days between 8-9 am, 3-5 pm), but were also evident on weekdays at other times and at weekends; they did not differ by gender or ethnic group. CONCLUSION: Active travel to school is associated with higher levels of objectively measured physical activity, particularly during periods of travel but also at other times. If children travelling by car were to achieve physical activity levels (steps) similar to children using active travel, they would increase their physical activity levels by 9%. However, the population increase would be a modest 2%, because of the low proportion of car travellers in this urban population

Screen time is associated with adiposity and insulin resistance in children

Higher screen time is associated with type 2 diabetes (T2D) risk in adults, but the association with T2D risk markers in children is unclear. We examined associations between self-reported screen time and T2D risk markers in children. Survey of 4495 children aged 9-10 years who had fasting cardiometabolic risk marker assessments, anthropometry measurements and reported daily screen time; objective physical activity was measured in a subset of 2031 children. Compared with an hour or less screen time daily, those reporting screen time over 3 hours had higher ponderal index (1.9%, 95% CI 0.5% to 3.4%), skinfold thickness (4.5%, 0.2% to 8.8%), fat mass index (3.3%, 0.0% to 6.7%), leptin (9.2%, 1.1% to 18.0%) and insulin resistance (10.5%, 4.9% to 16.4%); associations with glucose, HbA1c, physical activity and cardiovascular risk markers were weak or absent. Associations with insulin resistance remained after adjustment for adiposity, socioeconomic markers and physical activity. Strong graded associations between screen time, adiposity and insulin resistance suggest that reducing screen time could facilitate early T2D prevention. While these observations are of considerable public health interest, evidence from randomised controlled trials is needed to suggest causality. [Abstract copyright: Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

A Mixed Method Approach for Evaluating and Improving the Design of Learning in Puzzle Games

Despite the acknowledgment that learning is a necessary part of all gameplay, the area of Games User Research lacks an established evidence based method through which designers and researchers can understand, assess, and improve how commercial games teach players game-specific skills and information. In this paper, we propose a mixed method procedure that draws together both quantitative and experiential approaches to examine the extent to which players are supported in learning about the game world and mechanics. We demonstrate the method through presenting a case study of the game Portal involving 14 participants, who differed in terms of their gaming expertise. By comparing optimum solutions to puzzles against observed player performance, we illustrate how the method can indicate particular problems with how learning is structured within a game. We argue that the method can highlight where major breakdowns occur and yield design insights that can improve the player experience with puzzle games

Binary black hole initial data from matched asymptotic expansions

We present an approximate metric for a binary black hole spacetime to construct initial data for numerical relativity. This metric is obtained by asymptotically matching a post-Newtonian metric for a binary system to a perturbed Schwarzschild metric for each hole. In the inner zone near each hole, the metric is given by the Schwarzschild solution plus a quadrupolar perturbation corresponding to an external tidal gravitational field. In the near zone, well outside each black hole but less than a reduced wavelength from the center of mass of the binary, the metric is given by a post-Newtonian expansion including the lowest-order deviations from flat spacetime. When the near zone overlaps each inner zone in a buffer zone, the post-Newtonian and perturbed Schwarzschild metrics can be asymptotically matched to each other. By demanding matching (over a 4-volume in the buffer zone) rather than patching (choosing a particular 2-surface in the buffer zone), we guarantee that the errors are small in all zones. The resulting piecewise metric is made formally $C^\infty$ with smooth transition functions so as to obtain the finite extrinsic curvature of a 3-slice. In addition to the metric and extrinsic curvature, we present explicit results for the lapse and the shift, which can be used as initial data for numerical simulations. This initial data is not accurate all the way to the asymptotically flat ends inside each hole, and therefore must be used with evolution codes which employ black hole excision rather than puncture methods. This paper lays the foundations of a method that can be sraightforwardly iterated to obtain initial data to higher perturbative order.Comment: 24 pages, 15 figures. Replaced with published version. Major editing of text, no major change to the physic

Youth in Justice : Young People Explore What Their Role in Improving Youth Justice Might Be

This report, which was commissioned by the Centre for Youth & Criminal Justice and written by Space Unlimited, aims to understand how young people could become active participants in shaping improvements to youth justice policy, practice and research

Quantifying childhood fat mass: comparison of a novel height-and-weight-based prediction approach with DXA and bioelectrical impedance

Accurate assessment of childhood adiposity is important both for individuals and populations. We compared fat mass (FM) predictions from a novel prediction model based on height, weight and demographic factors (height–weight equation) with FM from bioelectrical impedance (BIA) and dual-energy X-ray absorptiometry (DXA), using the deuterium dilution method as a reference standard. FM data from all four methods were available for 174 ALSPAC Study participants, seen 2002–2003, aged 11–12-years. FM predictions from the three approaches were compared to the reference standard using; R2, calibration (slope and intercept) and root mean square error (RMSE). R2 values were high from ‘height–weight equation’ (90%) but lower than from DXA (95%) and BIA (91%). Whilst calibration intercepts from all three approaches were close to the ideal of 0, the calibration slope from the ‘height–weight equation’ (slope = 1.02) was closer to the ideal of 1 than DXA (slope = 0.88) and BIA (slope = 0.87) assessments. The ‘height–weight equation’ provided more accurate individual predictions with a smaller RMSE value (2.6 kg) than BIA (3.1 kg) or DXA (3.4 kg). Predictions from the ‘height–weight equation’ were at least as accurate as DXA and BIA and were based on simpler measurements and open-source equation, emphasising its potential for both individual and population-level FM assessments