Challenges of a community based pragmatic, randomised controlled trial of weight loss maintenance

Background Randomised controlled trials (RCTs) have a reputation for being inherently difficult to deliver as planned and often face unforeseen challenges and delays, particularly in relation to organisational and governance difficulties, participant interest, constraints due to allocation of costs, local investigator interest and lengthy bureaucracy. Recruitment is often difficult and the challenges faced often impact on the cost and delivery of a successful trial within the funded period. This paper reflects upon the challenges faced in delivering a pragmatic RCT of weight loss maintenance in a community setting and suggests some potential solutions. Methods The weight loss maintenance in adults trial aimed to evaluate the impact of a 12 month, individually tailored weight maintenance intervention on BMI 3 years from randomisation. Participants were recruited primarily from participant identification centres (PICs)—GP surgeries, exercise on referral schemes and slimming world. The intervention was delivered in community settings. A recruitment strategy implementation plan was drafted to address and monitor poor recruitment. Results Delays in opening and recruitment were experienced early on. Some were beyond the control of the study team such as; disagreement over allocation of national health service costs and PIC classification as well as difficulties in securing support from research networks. That the intervention was delivered in community settings was often at the root of these issues. Key items to address at the design stage of future trials include feasibility of eligibility criteria. The most effective element of the recruitment implementation plan was to refocus sources of recruitment and target only those who could fulfil the eligibility criteria immediately. Conclusions Learnings from this trial should be kept in mind by those designing similar studies in the future. Considering potential governance, cost and research network support implications at the design stage of pragmatic trials of any community-based complex intervention is paramount. The appropriateness and viability of inclusion criteria also require careful consideration as does use of a targeted advertising strategy

A Chandra Study of Temperature Substructures in Intermediate-Redshift Galaxy Clusters

By analyzing the gas temperature maps created from the Chandra archive data, we reveal the prevailing existence of temperature substructures on ~100 kpc scales in the central regions of nine intermediate-redshift (z~0.1) galaxy clusters, which resemble those found in the Virgo and Coma Clusters. Each substructure contains a clump of hot plasma whose temperature is about 2-3 keV higher than the environment, corresponding to an excess thermal energy of ~1E58-1E60 erg per clump. Since if there were no significant non-gravitational heating sources, these substructures would have perished in 1E8-1E9 yrs due to thermal conduction and turbulent flows, whose velocity is found to range from about 200 to 400 km/s, we conclude that the substructures cannot be created and sustained by inhomogeneous radiative cooling. We also eliminate the possibilities that the temperature substructures are caused by supernova explosions, or by the non-thermal X-ray emission due to the inverse-Comptonization of the CMB photons. By calculating the rising time of AGN-induced buoyant bubbles, we speculate that the intermittent AGN outbursts (~ 1E60 erg per burst) may have played a crucial role in the forming of the high temperature substructures. Our results are supported by recent study of McNamara & Nulsen (2007), posing a tight observational constraint on future theoretical and numerical studies.Comment: 31 pages, 7 figures, ApJ accepte

Electronic Contract Administration – Legal and Security Issues Research Report

This Report is a deliverable for the CRC for Construction Innovation research project 2005-025-A Electronic Contract Administration – Legal and Security Issues. It considers the security and legal risks that result from the increasing adoption of information and communication technologies (ICT) in the construction industry for e-contracting purposes and makes recommendations to minimise those risks

Distribution of sialic acids on mucins and gels: a defense mechanism

Moist mucosal epithelial interfaces that are exposed to external environments are dominated by sugar epitopes, some of which (e.g., sialic acids) are involved in host defense. In this study, we determined the abundance and distribution of two sialic acids to assess differences in their availability to an exogenous probe in isolated mucins and mucous gels. We used atomic force microscopy to obtain force maps of human preocular mucous and purified ocular mucins by probing and locating the interactions between tip-tethered lectins Maackia amurensis and Sambucus nigra and their respective receptors, α-2,3 and α-2,6 N-acetylneuraminic (sialic) acids. The rupture force distributions were not affected by neighboring sugar-bearing molecules. Energy contours for both lectin-sugar bonds were fitted to a two-barrier model, suggesting a conformational change before dissociation. In contrast to data from purified mucin molecules, the preocular gels presented numerous large clusters (19,000 ± 4000 nm2) of α-2,6 sialic acids, but very few small clusters (2000 ± 500 nm2) of α-2,3 epitopes. This indicates that mucins, which are rich in α-2,3 sialic acids, are only partially exposed at the surface of the mucous gel. Microorganisms that recognize α-2,3 sialic acids will encounter only isolated ligands, and the adhesion of other microorganisms will be enhanced by large islands of neighboring α-2,6 sialic acids. We have unveiled an additional level of mucosal surface heterogeneity, specifically in the distribution of pro- and antiadhesive sialic acids that protect underlying epithelia from viruses and bacteria

Metal transport by gas sloshing in M87

We present the results of an XMM-Newton mosaic covering the central ~200 kpc of the nearby Virgo cluster. We focus on a strong surface brightness discontinuity in the outskirts of the brightest cluster galaxy, M87. Using both XMM-Newton and Suzaku, we derive accurate temperature and metallicity profiles across this feature and show that it is a cold front probably due to sloshing of the Virgo ICM. It is also associated with a discontinuity in the chemical composition. The gas in the inner, bright region of the front is ~40% more abundant in Fe than the gas outside the front, suggesting the important role of sloshing in transporting metals through the ICM. For the first time, we provide a quantitative estimate of the mass of Fe transported by a cold front. This amounts to ~6% of the total Fe mass within the radial range affected by sloshing, significantly more than the amount of metals transported by the AGN in the same cluster core. The very low Fe abundance of only ~0.2 solar immediately outside the cold front at a radius of 90 kpc suggests we are witnessing first-hand the transport of higher metallicity gas into a pristine region, whose abundance is typical of the cluster outskirts. The Mg/Fe and O/Fe abundance ratios remain approximately constant over the entire radial range between the centre of M87 and the faint side of the cold front, which requires the presence of a centrally peaked distribution not only for Fe but also for core-collapse type supernova products. This peak may stem from the star formation triggered as the BCG assembled during the protocluster phase.Comment: accepted for publication in MNRA

Inhaled hypertonic saline in infants and toddlers with cystic fibrosis: short-term tolerability, adherence, and safety

Inhaled hypertonic saline (HS) is an attractive agent for chronic maintenance therapy in infants and toddlers with cystic fibrosis (CF) because it improves defective mucociliary clearance. Prior to undertaking a clinical trial of HS efficacy in young children with CF, tolerability, adherence and safety must be established

Las distintas movilidades de las comunidades en las islas del Pacífico

Los tipos de movilidad en las islas del Pacífico son varios y distintos. Los estudios de caso en la región nos permiten ver cuáles son las acciones y las voluntades de las personas, los hogares y las comunidades a la luz de una vulnerabilidad por cuestiones climáticas en rápido aumento

Inositol polyphosphate derivative inhibits Na + transport and improves fluid dynamics in cystic fibrosis airway epithelia

Amiloride-sensitive, epithelial Na+ channel (ENaC)-mediated, active absorption of Na+ is elevated in the airway epithelium of cystic fibrosis (CF) patients, resulting in excess fluid removal from the airway lumen. This excess fluid/volume absorption corresponds to CF transmembrane regulator-linked defects in ENaC regulation, resulting in the reduced mucociliary clearance found in CF airways. Herein we show that INO-4995, a synthetic analog of the intracellular signaling molecule, D-myo-inositol 3,4,5,6-tetrakisphosphate, inhibits Na+ and fluid absorption across CF airway epithelia, thus alleviating this critical pathology. This conclusion was based on electrophysiological studies, fluid absorption, and 22Na+ flux measurements in CF airway epithelia, contrasted with normal epithelia, and on electrophysiological studies in Madin-Darby canine kidney cells and 3T3 cells overexpressing ENaC. The effects of INO-4995 were long-lasting, dose-dependent, and more pronounced in epithelia from CF patients vs. controls. These findings support preclinical development of INO-4995 for CF treatment and demonstrate for the first time the therapeutic potential of inositol polyphosphate derivatives