A qualitative analysis of the enforcement of the regulation of nutrition and health claims made for foods and its implications for health

This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. In common with local government organisations across the world, local authorities in the UK have responsibility for promoting health. A key part of this function is the frontline enforcement activities of officers responsible for compliance with health and nutrition claims. This study identifies attitudes, values and practices of enforcers: namely trading standards and environmental health officers, when faced with the problem of non-compliance with the Regulation. Semi-structured interviews with frontline enforcers from local authority regulatory services to investigate challenges with the enforcement of Regulation (EC) 1924/2006. Twenty participants were interviewed; sixteen were based in North West England and two in the North and two in the South of England. The participants were selected for their specialist knowledge and experience of enforcement of nutrition and health claims. Regulation (EC) No. 1924/2006 on nutrition and health claims presents particular challenges for enforcers seeking to apply an optimal strategy to flawed regulatory design. As with other regulations, when faced with non-compliance, enforcers, specifically trading standards and environmental health officers have a wide discretion to determine their response: ranging from the deterrent or accommodative styles of enforcement. The participants reported using advice rather than action and by doing so confronting their bifurcating identity of prosecutor and advisor. Enforcers used advice as a regulatory tool in enforcing the law relating to nutrition and health claims

An Integrated Approach to the Determination and Consequences of Residual Stress on the Fatigue Performance of Welded Aircraft Structures.

Although residual stress in welded structures and components has long been known to have an effect on their fatigue performance, access to reliable, spatially accurate residual stress field data has been limited. Recent advances in neutron and synchrotron X-ray diffraction allow a far more detailed picture of weld residual stress fields to be obtained that permits the development and use of predictive models that can be used for accurate design against fatigue in aircraft structures. This paper describes a fully integrated study of the three- dimensional residual stress distribution accompanying state-of-the-art fusion welds in 2024-T4 aluminum alloy, and how it is affected by subsequent machining and service loading. A particular feature of this work has been the development of techniques allowing the nondestructive evaluation of the residual stress field in the full range of specimens used to provide the design data required for welded aircraft structures and the integration of this information into all aspects of damage tolerant design

Discovery and Optimization of Small-Molecule Ligands for the CBP/p300 Bromodomains

Small-molecule inhibitors that target bromodomains outside of the bromodomain and extra-terminal (BET) sub-family are lacking. Here, we describe highly potent and selective ligands for the bromodomain module of the human lysine acetyl transferase CBP/p300, developed from a series of 5-isoxazolyl-benzimidazoles. Our starting point was a fragment hit, which was optimized into a more potent and selective lead using parallel synthesis employing Suzuki couplings, benzimidazole-forming reactions, and reductive aminations. The selectivity of the lead compound against other bromodomain family members was investigated using a thermal stability assay, which revealed some inhibition of the structurally related BET family members. To address the BET selectivity issue, X-ray crystal structures of the lead compound bound to the CREB binding protein (CBP) and the first bromodomain of BRD4 (BRD4(1)) were used to guide the design of more selective compounds. The crystal structures obtained revealed two distinct binding modes. By varying the aryl substitution pattern and developing conformationally constrained analogues, selectivity for CBP over BRD4(1) was increased. The optimized compound is highly potent (Kd = 21 nM) and selective, displaying 40-fold selectivity over BRD4(1). Cellular activity was demonstrated using fluorescence recovery after photo-bleaching (FRAP) and a p53 reporter assay. The optimized compounds are cell-active and have nanomolar affinity for CBP/p300; therefore, they should be useful in studies investigating the biological roles of CBP and p300 and to validate the CBP and p300 bromodomains as therapeutic targets