Prolonged expression of the γ-H2AX DNA repair biomarker correlates with excess acute and chronic toxicity from radiotherapy treatment

The normal tissue tolerance levels to fractionated radiotherapy have been appreciated by a century of careful clinical observations and radiobiological studies in animals. During clinical fractionated radiotherapy, these normal tissue tolerance levels are respected, and severe sequelae of radiotherapy are avoided in the majority of patients. Notwithstanding, a minority of patients experience unexpectedly severe normal tissue reactions. The ability to predict which patients might form this minority would be important. We have conducted a study to develop a rapid and reliable diagnostic test to predict excessive normal tissue toxicity (NTT) in radiotherapy patients. A flow cytometric immunocytochemical assay was used to measure DNA damage in peripheral blood lymphocytes (PBL) from cancer patients exposed to 2-Gy gamma radiation. DNA damage and repair was measured by induction of cellular γ-H2AX in unirradiated and exposed cells at specific time points following exposure. In 12 cancer patients that experienced severe atypical NTT following radiotherapy, there was a failure to repair DNA double-strand breaks (DSB) as measured by γ-H2AX induction and persistence. In ten cancer patients that experienced little or no NTT and in seven normal (noncancer controls), efficient repair of DNA DSB was observed in the γ-H2AX assay. We conclude that a flow cytometric assay based on γ-H2AX induction in PBL of radiotherapy patients may represent a robust, rapid and reliable biomarker to predict NTT during radiotherapy. Further research is required with a larger patient cohort to validate this important study

The role of invariant Natural Killer T cells in SLE patients with atherosclerosis

Accelerated atherosclerosis is a complication of the rheumatic disease systemic lupus erythematosus (SLE). I questioned the role of invariant Natural Killer T (iNKT) cells in this process, since they are known to be defective in SLE but also promote atherosclerosis in response to CD1d-mediated lipid presentation. SLE patients with asymptomatic plaque (SLE-P) had an altered iNKT cell phenotype to those without plaque (SLE-NP), characterised by differences in activation marker expression and increased IL-4. This SLE-P iNKT cell phenotype correlated with differences in serum lipids including VLDL and coud be recapitulated in vitro by culturing healthy PBMCs with serum from SLE-P patients, an effect that was inhibited in the presence of anti-CD1d. Whilst differences in CD1d and lipid raft co-localisation and recycling were found in SLE patients, no difference was observed between SLE-NP and SLE-P patients. Isolation of phospholipids from SLE-P patients confirmed that differences in the lipids being presented were driving the anti-inflammatory iNKT cell phenotype in SLE-P patients. The finding that healthy iNKT cells, differentiated in the presence of healthy monocytes and serum from SLE-P patients, could induce THP-1 macrophage polarisation towards an anti-inflammatory M2-like phenotype suggested a protective role for iNKT cells in SLE patients with subclinical atherosclerosis. This was confirmed by studying a group of SLE patients who had suffered a cardiovascular event, where this protective iNKT cell phenotype seen in asymptomatic patients was lost

Are changes in breeding habitat responsible for recent population changes of long-distance migrant birds?

Capsule: The direction and magnitude of changes in structure of UK woodlands since the 1980s, are inconsistent with them playing a causative role in the declines of four migrant bird species in upland oak woods. / Aims: To investigate whether changes in woodland structure were a possible cause of population changes of four Afro-Palearctic migrants (Wood Warbler Phylloscopus sibilatrix, Tree Pipit Anthus trivialis, Pied Flycatcher Ficedula hypoleuca and Common Redstart Phoenicurus phoenicurus) in the upland oakwoods of western and northern Britain. / Methods: Bird population estimates and measures of woodland structure were recorded in two time periods 1982–85 and 2003–04 across six regions of the UK. We modelled the effect of habitat change and initial habitat state on population changes between the two time periods. The predicted effects of habitat change on populations were then compared with observed population changes across the different regions. / Results: All four species underwent population declines; there were also significant increases in ground cover and understorey cover. The number of birds in 2003–04 was influenced by habitat structure at this time in addition to showing regional differences. Change in bird numbers varied between regions and was affected by both the initial habitat state and change in habitat structure, with regional variation in the effect of habitat change. There was however no relationship between the predicted effect of change in habitat structure on population size and observed regional population changes. / Conclusions: Changes in woodland structure are unlikely to be the main driver of population change in these four migrant bird species, and large-scale factors affecting demographics in other parts of their breeding range or in their wintering areas are likely reasons for local population declines

The Management and Use of Social Network Sites in a Government Department

In this paper we report findings from a study of social network site use in a UK Government department. We have investigated this from a managerial, organisational perspective. We found at the study site that there are already several social network technologies in use, and that these: misalign with and problematize organisational boundaries; blur boundaries between working and social lives; present differing opportunities for control; have different visibilities; have overlapping functionality with each other and with other information technologies; that they evolve and change over time; and that their uptake is conditioned by existing infrastructure and availability. We find the organisational complexity that social technologies are often hoped to cut across is, in reality, something that shapes their uptake and use. We argue the idea of a single, central social network site for supporting cooperative work within an organisation will hit the same problems as any effort of centralisation in organisations. We argue that while there is still plenty of scope for design and innovation in this area, an important challenge now is in supporting organisations in managing what can best be referred to as a social network site 'ecosystem'.Comment: Accepted for publication in JCSCW (The Journal of Computer Supported Cooperative Work

Mobilisation kinetics of Br, Cd, Cr, Hg, Pb and Sb in microplastics exposed to simulated, dietary-adapted digestive conditions of seabirds

12 month embarg

The Next Big Match: Convergence, Competition and Sports Media Rights

Using examples from a number of different European countries, this article analyses the increasingly prominent position of traditional telecommunications companies, such as British Telecom (UK), Deutsche Telekom (Germany), France Telecom/Orange (France) and Telefonica (Spain), in the contemporary sports media rights market. The first part of the article examines the commercial strategies of telecommunications operators and highlights how their acquisition of sports rights has been driven by the need to ensure a competitive position within an increasingly converged communications market. The second part of the article then moves on to consider the regulation of the sports media rights market. Most significantly, this section emphasises the need for further regulatory intervention to ensure that increased competition for sports rights leads to improved services and lower prices for consumers, rather than merely endlessly spiralling fees for the exclusive ownership of premium rights that are then passed on to sports channel and/or broadband subscribers

Experiences of physical activity: A phenomenological study of individuals with cystic fibrosis

Although extensive research has investigated the benefits of physical activity in cystic fibrosis, minimal exploration of the experiences for individuals from a qualitative, phenomenological perspective has been carried out. The aim of this study was to explore the subjective experiences of physical activity for individuals with cystic fibrosis. The health-care team, at an Adult Cystic Fibrosis Unit in the United Kingdom, recruited 12 participants to take part. Interview data were analysed using interpretative phenomenological analysis. A central theme of ‘self-monitoring’ emerged from the accounts and was embedded in the three super-ordinate themes

Linking forest cover, soil erosion and mire hydrology to late-Holocene human activity and climate in NW Spain

This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 3.0 License (http://www.creativecommons.org/licenses/by-nc/3.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access page (http://www.uk.sagepub.com/aboutus/openaccess.htm).This article has been made available through the Brunel Open Access Publishing Fund.Forest clearance is one of the main drivers of soil erosion and hydrological changes in mires, although climate may also play a significant role. Because of the wide range of factors involved, understanding these complex links requires long-term multi-proxy approaches and research on the best proxies to focus. A peat core from NW Spain (Cruz do Bocelo mire), spanning the last ~3000 years, has been studied at high resolution by physical (density and loss on ignition (LOI)), geochemical (elemental composition) and palynological (pollen and non-pollen palynomorphs) analyses. Proxies related to mineral matter fluxes from the catchment (lithogenic tracers, Glomus and Entorrhiza), rainfall (Bromine), mire hydrology (HdV-18), human pressure (Cerealia-type, nitrophilous taxa and coprophilous fungi) and forest cover (mesophilous tree taxa) were the most useful to reconstruct the evolution of the mire and its catchment. Forest clearance for farming was one of the main drivers of environmental change from at least the local Iron Age (~2685 cal. yr BP) onwards. The most intense phase of deforestation occurred during Roman and Germanic times and the late Middle Ages. During these phases, the entire catchment was affected, resulting in enhanced soil erosion and severe hydrological modifications of the mire. Climate, especially rainfall, may have also accelerated these processes during wetter periods. However, it is noteworthy that the hydrology of the mire seems to have been insensitive to rainfall variations when mesophilous forest dominated. Abrupt changes were only detected once intense forest clearance commenced during the Iron Age/Roman transition (~2190 cal. yr BP) phase, which represented a tipping point in catchment's ability to buffer impacts. Overall, our findings highlight the importance of studying ecosystems' long-term trajectories and catchment-wide processes when implementing mire habitat protection measures.This work was funded by the projects CGL2010-20672 (Plan Nacional I+D+i, Spanish Ministry of Science and Innovation) and 10PXIB200182PR (General Directorate of I+D, Xunta de Galicia). N Silva-Sánchez and L López-Merino are currently supported by a FPU predoctoral scholarship (AP2010-3264) funded by the Spanish Government and a MINT postdoctoral fellowship funded by the Brunel Institute for the Environment, respectively

Preliminary interpretation of Titan plasma interaction as observed by the Cassini Plasma Spectrometer: Comparisons with Voyager 1

The Cassini Plasma Spectrometer (CAPS) instrument observed the plasma environment at Titan during the Cassini orbiter's TA encounter on October 26, 2004. Titan was in Saturn's magnetosphere during the Voyager 1 flyby and also during the TA encounter. CAPS measurements from this encounter are compared with measurements made by the Voyager 1 Plasma Science Instrument (PLS). The comparisons focus on the composition and nature of ambient and pickup ions. They lead to: A) the major ion components of Saturn's magnetosphere in the vicinity of Titan are H+, H-2(+) and O+/CH4+ ions; B) finite gyroradius effects are apparent in ambient O+ ions as the result of their absorption by Titan's extended atmosphere; C) the principal pickup ions are composed of H+, H-2(+), N+/CH2+, CH4+, and N-2(+); D) the pickup ions are in narrow energy ranges; and E) there is clear evidence of the slowing down of background ions due to pickup ion mass loading

Livestock trade networks for guiding animal health surveillance

BACKGROUND: Trade in live animals can contribute to the introduction of exotic diseases, the maintenance and spread endemic diseases. Annually millions of animals are moved across Europe for the purposes of breeding, fattening and slaughter. Data on the number of animals moved were obtained from the Directorate General Sanco (DG Sanco) for 2011. These were converted to livestock units to enable direct comparison across species and their movements were mapped, used to calculate the indegrees and outdegrees of 27 European countries and the density and transitivity of movements within Europe. This provided the opportunity to discuss surveillance of European livestock movement taking into account stopping points en-route. RESULTS: High density and transitivity of movement for registered equines, breeding and fattening cattle, breeding poultry and pigs for breeding, fattening and slaughter indicates that hazards have the potential to spread quickly within these populations. This is of concern to highly connected countries particularly those where imported animals constitute a large proportion of their national livestock populations, and have a high indegree. The transport of poultry (older than 72 hours) and unweaned animals would require more rest breaks than the movement of weaned animals, which may provide more opportunities for disease transmission. Transitivity is greatest for animals transported for breeding purposes with cattle, pigs and poultry having values of over 50%. CONCLUSIONS: This paper demonstrated that some species (pigs and poultry) are traded much more frequently and at a larger scale than species such as goats. Some countries are more vulnerable than others due to importing animals from many countries, having imported animals requiring rest-breaks and importing large proportions of their national herd or flock. Such knowledge about the vulnerability of different livestock systems related to trade movements can be used to inform the design of animal health surveillance systems to facilitate the trade in animals between European member states. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12917-015-0354-4) contains supplementary material, which is available to authorized users