The speed of increasing milk feeds: a randomised controlled trial

BACKGROUND In the UK, 1-2% of infants are born very preterm (<32 weeks of gestation) or have very low birth weight (<1500 g). Very preterm infants are initially unable to be fed nutritional volumes of milk and therefore require intravenous nutrition. Milk feeding strategies influence several long and short term health outcomes including growth, survival, infection (associated with intravenous nutrition) and necrotising enterocolitis (NEC); with both infection and NEC being key predictive factors of long term disability. Currently there is no consistent strategy for feeding preterm infants across the UK. The SIFT trial will test two speeds of increasing milk feeds with the primary aim of determining effects on survival without moderate or severe neurodevelopmental disability at 24 months of age, corrected for prematurity. The trial will also examine many secondary outcomes including infection, NEC, time taken to reach full feeds and growth. METHODS/DESIGN Two thousand eight hundred very preterm or very low birth weight infants will be recruited from approximately 30 hospitals across the UK to a randomised controlled trial. Infants with severe congenital anomaly or no realistic chance of survival will be excluded. Infants will be randomly allocated to either a faster (30 ml/kg/day) or slower (18 ml/kg/day) rate of increase in milk feeds. Data will be collected during the neonatal hospital stay on weight, infection rates, episodes of NEC, length of stay and time to reach full milk feeds. Long term health outcomes comprising vision, hearing, motor and cognitive impairment will be assessed at 24 months of age (corrected for prematurity) using a parent report questionnaire. DISCUSSION Extensive searches have found no active or proposed studies investigating the rate of increasing milk feeds. The results of this trial will have importance for optimising incremental milk feeding for very preterm and/or very low birth weight infants. No additional resources will be required to implement an optimal feeding strategy, and therefore if successful, the trial results could rapidly be adopted across the NHS at low cost. TRIAL REGISTRATION ISRCTN Registry; ISRCTN76463425 on 5 March, 2013

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

Barriers and facilitators to development and implementation of a rural primary health care intervention for dementia: a process evaluation

Abstract Background With rural population aging there are growing numbers of people with dementia in rural and remote settings. The role of primary health care (PHC) is critical in rural locations, yet there is a lack of rural-specific PHC models for dementia, and little is known about factors influencing the development, implementation, and sustainability of rural PHC interventions. Using a community-based participatory research approach, researchers collaborated with a rural PHC team to co-design and implement an evidence-based interdisciplinary rural PHC memory clinic in the Canadian province of Saskatchewan. This paper reports barriers and facilitators to developing, implementing, and sustaining the intervention. Methods A qualitative longitudinal process evaluation was conducted over two and half years, from pre- to post-implementation. Data collection and analyses were guided by the Consolidated Framework for Implementation Research (CFIR) which consists of 38 constructs within five domains: innovation characteristics, outer setting, inner setting, individual characteristics, and process. Data were collected via focus groups with the PHC team and stakeholders, smaller team workgroup meetings, and team member interviews. Analysis was conducted using a deductive approach to apply CFIR codes to the data and an inductive analysis to identify barriers and facilitators. Results Across all domains, 14 constructs influenced development and implementation. Three domains (innovation characteristics, inner setting, process) were most important. Facilitators were the relative advantage of the intervention, ability to trial on a small scale, tension for change, leadership engagement, availability of resources, education and support from researchers, increased self-efficacy, and engagement of champions. Barriers included the complexity of multiple intervention components, required practice changes, lack of formal incentive programs, time intensiveness of modifying the EMR during iterative development, lack of EMR access by all team members, lack of co-location of team members, workload and busy clinical schedules, inability to justify a designated dementia care manager role, and turnover of PHC team members. Conclusions The study identified key factors that supported and hindered the development and implementation of a rural-specific strategy for dementia assessment and management in PHC. Despite challenges related to the rural context, the researcher-academic partnership was successful in developing and implementing the intervention

The phsiological structure of human C-reactive protein and its complex with phosphocholine

AbstractBackground: Human C-reactive protein (CRP) is the classical acute phase reactant, the circulating concentration of which rises rapidly and extensively in a cytokine-mediated response to tissue injury, infection and inflammation. Serum CRP values are routinely measured, empirically, to detect and monitor many human diseases. However, CRP is likely to have important host defence, scavenging and metabolic functions through its capacity for calcium-dependent binding to exogenous and autologous molecules containing phosphocholine (PC) and then activating the classical complement pathway. CRP may also have pathogenic effects and the recent discovery of a prognostic association between increased CRP production and coronary atherothrombotic events is of particular interest.Results: The X-ray structures of fully calcified C-reactive protein, in the presence and absence of bound PC, reveal that although the subunit β-sheet jellyroll fold is very similar to that of the homologous pentameric protein serum amyloid P component, each subunit is tipped towards the fivefold axis. PC is bound in a shallow surface pocket on each subunit, interacting with the two protein-bound calcium ions via the phosphate group and with Glu81 via the choline moiety. There is also an unexpected hydrophobic pocket adjacent to the ligand.Conclusions: The structure shows how large ligands containing PC may be bound by CRP via a phosphate oxygen that projects away from the surface of the protein. Multipoint attachment of one planar face of the CRP molecule to a PC-bearing surface would leave available, on the opposite exposed face, the recognition sites for C1q, which have been identified by mutagenesis. This would enable CRP to target physiologically and/or pathologically significant complement activation. The hydrophobic pocket adjacent to bound PC invites the design of inhibitors of CRP binding that may have therapeutic relevance to the possible role of CRP in atherothrombotic events