Spatio-temporal analysis of DNA damage repair using the X-ray microbeam

Cellular response to radiation damage is made by a complex network of pathways and feedback loops whose spatiotemporal organization is still unclear despite its decisive role in determining the fate of the damaged cell. The single-cell approach and the high spatial resolution offered by microbeams provide the perfect tool to study and quantify the dynamic processes associated with the induction and repair of DNA damage. The soft X-ray microbeam has been used to follow the development of radiation induced foci in live cells by monitoring their size and intensity as a function of dose and time using yellow fluorescent protein (YFP) tagging techniques. Preliminary data indicate a delayed and linear rising of the intensity signal indicating a slow kinetic for the accumulation of DNA repair protein 53BP1. A slow and limited foci diffusion has also been observed. Further investigations are required to assess whatever such diffusion is consistent with a random walk pattern or if it is the result of a more structured lesion processing phenomenon. In conclusion, our data indicates that the use of microbeams coupled to live cell microscopy represent a sophisticated approach for visualizing and quantifying the dynamics changes of DNA proteins at the damaged sites.

Spatial Mobility Intentions, the Labour Market and Incapacity Benefit Claimants Evidence from Northern Ireland

The paper analyses the work-related spatial mobility intentions of incapacity benefit (IB) claimants in Northern Ireland using a new survey dataset. Greater understanding of the prospective mobility of benefit claimants contributes to debates about employability, inclusion in the labour market and arguments about spatial mismatch. The analysis finds that IB claimants are not markedly less mobile than other population groups; that mobility is shaped by age, level of qualification, illness type, ability to drive and motivation; and that geography is important in several ways. The paper concludes by arguing that limited spatial mobility is a good indicator of disadvantage and that spatial mobility should be placed nearer the centre of the design and delivery of labour market policy

Population dynamics of the liver fluke, Fasciola hepatica: the effect of time and spatial separation on the genetic diversity of fluke populations in the Netherlands

An evaluation of the genetic diversity within Fasciola hepatica (liver fluke) may provide an insight into its potential to respond to environmental changes, such as anthelmintic use or climate change. In this study, we determined the mitochondrial DNA haplotypes of >400 flukes from 29 individual cattle, from 2 farms in the Netherlands, as an exemplar of fasciolosis in a European context. Analysis of this dataset has provided us with a measure of the genetic variation within infrapopulations (individual hosts) and the diversity between infrapopulations within a herd of cattle. Temporal sampling from one farm allowed for the measurement of the stability of genetic variation at a single location, whilst the comparison between the two farms provided information on the variation in relation to distance and previous anthelmintic regimes. We showed that the liver fluke population in this region is predominantly linked to 2 distinct clades. Individual infrapopulations contain a leptokurtic distribution of genetically diverse flukes. The haplotypes present on a farm have been shown to change significantly over a relatively short time-period.

The Architecture of Home in Cairo: Socio-Spatial Practice of the Hawari's Everyday Life

The hawari of Cairo - narrow non-straight alleyways - are the basic urban units that have formed the medieval city since its foundation back in 969 AD. Until early in the C20th, they made up the primary urban divisions of the city and were residential in nature. Contemporary hawari, by contrast, are increasingly dominated by commercial and industrial activity. This medieval urban maze of extremely short, broken, zigzag streets and dead ends are defensible territories, powerful institutions, and important social systems. While the hawari have been studied as an exemplar for urban structure of medieval Islamic urbanism, and as individual building typologies, this book is the first to examine in detail the socio-spatial practice of the architecture of home in the city. It investigates how people live, communicate and relate to each other within their houses or shared spaces of the alleys, and in doing so, to uncover several new socio-spatial dimensions and meanings in this architectural form.

In an attempt to re-establish the link between architecture past and present, and to understand the changing social needs of communities, this book uncovers the notion of home as central to understand architecture in such a city with long history as Cairo. It firstly describes the historical development of the domestic spaces (indoor and outdoor), and provides an inclusive analysis of spaces of everyday activities in the hawari of old Cairo. It then broadens its analysis to other parts of the city, highlighting different customs and representations of home in the city at large. Cairo, in the context of this book, is represented as the most sophisticated urban centre in the Middle East with different and sometimes contrasting approaches to the architecture of home, as a practice and spatial system.

In order to analyse the complexity and interconnectedness of the components and elements of the hawari as a 'collective home', it layers its narratives of architectural and social developments as a domestic environment over the past two hundred years, and in doing so, explores the in-depth social meaning and performance of spaces, both private and public.

The spatial distribution of Holocene cryptotephras in north-west Europe since 7 ka: implications for understanding ash fall events from Icelandic eruptions

We present distribution maps for all cryptotephras (distal volcanic ash layers) younger than 7 ka that have been reported from three or more lakes or peatlands in north-west Europe. All but one of the tephras originates from Iceland; the exception has been attributed to Jan Mayen. We find strong spatial patterning in tephra occurrence at the landscape scale; most, but not all of the tephra occurrences are significantly spatially clustered, which likely reflects atmospheric and weather patterns at the time of the eruptions. Contrary to expectations based on atmospheric modelling studies, tephras appear to be at least as abundant in Ireland and northern Scotland as in Scandinavia. Rhyolitic and other felsic tephras occur in lakes and peatlands throughout the study region, but andesitic and basaltic tephras are largely restricted to lake sites in the Faroe Islands and Ireland. Explanations of some of these patterns will require further research on the effects of different methodologies for locating and characterizing cryptotephras. These new maps will help to guide future investigations in tephrochronology and volcanic hazard analysis.

A Monte Carlo model of DNA double-strand break clustering and rejoining kinetics for the analysis of pulsed-field gel electrophoresis data

In studies of radiation-induced DNA fragmentation and repair, analytical models may provide rapid and easy-to-use methods to test simple hypotheses regarding the breakage and rejoining mechanisms involved. The random breakage model, according to which lesions are distributed uniformly and independently of each other along the DNA, has been the model most used to describe spatial distribution of radiation-induced DNA damage. Recently several mechanistic approaches have been proposed that model clustered damage to DNA. In general, such approaches focus on the study of initial radiation-induced DNA damage and repair, without considering the effects of additional (unwanted and unavoidable) fragmentation that may take place during the experimental procedures. While most approaches, including measurement of total DNA mass below a specified value, allow for the occurrence of background experimental damage by means of simple subtractive procedures, a more detailed analysis of DNA fragmentation necessitates a more accurate treatment. We have developed a new, relatively simple model of DNA breakage and the resulting rejoining kinetics of broken fragments. Initial radiation-induced DNA damage is simulated using a clustered breakage approach, with three free parameters: the number of independently located clusters, each containing several DNA double-strand breaks (DSBs), the average number of DSBs within a cluster (multiplicity of the cluster), and the maximum allowed radius within which DSBs belonging to the same cluster are distributed. Random breakage is simulated as a special case of the DSB clustering procedure. When the model is applied to the analysis of DNA fragmentation as measured with pulsed-field gel electrophoresis (PFGE), the hypothesis that DSBs in proximity rejoin at a different rate from that of sparse isolated breaks can be tested, since the kinetics of rejoining of fragments of varying size may be followed by means of computer simulations. The problem of how to account for background damage from experimental handling is also carefully considered. We have shown that the conventional procedure of subtracting the background damage from the experimental data may lead to erroneous conclusions during the analysis of both initial fragmentation and DSB rejoining. Despite its relative simplicity, the method presented allows both the quantitative and qualitative description of radiation-induced DNA fragmentation and subsequent rejoining of double-stranded DNA fragments. (C) 2004 by Radiation Research Society.

Effect of radiotherapy after breast-conserving surgery on 10-year recurrence and 15-year breast cancer death: meta-analysis of individual patient data for 10,801 women in 17 randomised trials

Background: After breast-conserving surgery, radiotherapy reduces recurrence and breast cancer death, but it may do so more for some groups of women than for others. We describe the absolute magnitude of these reductions according to various prognostic and other patient characteristics, and relate the absolute reduction in 15-year risk of breast cancer death to the absolute reduction in 10-year recurrence risk.
Methods: We undertook a meta-analysis of individual patient data for 10?801 women in 17 randomised trials of radiotherapy versus no radiotherapy after breast-conserving surgery, 8337 of whom had pathologically confirmed node-negative (pN0) or node-positive (pN+) disease.
Findings: Overall, radiotherapy reduced the 10-year risk of any (ie, locoregional or distant) first recurrence from 35·0% to 19·3% (absolute reduction 15·7%, 95% CI 13·7–17·7, 2p<0·00001) and reduced the 15-year risk of breast cancer death from 25·2% to 21·4% (absolute reduction 3·8%, 1·6–6·0, 2p=0·00005). In women with pN0 disease (n=7287), radiotherapy reduced these risks from 31·0% to 15·6% (absolute recurrence reduction 15·4%, 13·2–17·6, 2p<0·00001) and from 20·5% to 17·2% (absolute mortality reduction 3·3%, 0·8–5·8, 2p=0·005), respectively. In these women with pN0 disease, the absolute recurrence reduction varied according to age, grade, oestrogen-receptor status, tamoxifen use, and extent of surgery, and these characteristics were used to predict large (=20%), intermediate (10–19%), or lower (<10%) absolute reductions in the 10-year recurrence risk. Absolute reductions in 15-year risk of breast cancer death in these three prediction categories were 7·8% (95% CI 3·1–12·5), 1·1% (–2·0 to 4·2), and 0·1% (–7·5 to 7·7) respectively (trend in absolute mortality reduction 2p=0·03). In the few women with pN+ disease (n=1050), radiotherapy reduced the 10-year recurrence risk from 63·7% to 42·5% (absolute reduction 21·2%, 95% CI 14·5–27·9, 2p<0·00001) and the 15-year risk of breast cancer death from 51·3% to 42·8% (absolute reduction 8·5%, 1·8–15·2, 2p=0·01). Overall, about one breast cancer death was avoided by year 15 for every four recurrences avoided by year 10, and the mortality reduction did not differ significantly from this overall relationship in any of the three prediction categories for pN0 disease or for pN+ disease.
Interpretation: After breast-conserving surgery, radiotherapy to the conserved breast halves the rate at which the disease recurs and reduces the breast cancer death rate by about a sixth. These proportional benefits vary little between different groups of women. By contrast, the absolute benefits from radiotherapy vary substantially according to the characteristics of the patient and they can be predicted at the time when treatment decisions need to be made.
Funding: Cancer Research UK, British Heart Foundation, and UK Medical Research Council.

Confined site construction: An empirical analysis of factors impacting health and safety management

Purpose – The purpose of this paper is to identify, clarify and tabulate the various managerial issues encountered, to aid in the management of the complex health and safety concerns which occur within a confined construction site environment.

Design/methodology/approach – This is achieved through conducting extensive qualitative and qualitative research in the form of case studies, interviews and questionnaire survey.

Findings – The leading managerial issues in the management of health and safety on a confined construction site are found to be: “Difficulty to move materials around site safely”; “Lack of adequate room for the effective handling of materials”; “Difficulty in ensuring site is tidy and all plant and materials are stored safely”; “Close proximity of individuals to operation of large plant and machinery”; and joint fifth “Difficulty in ensuring proper arrangement and collection of waste materials on-site” along with “Difficulty in controlling hazardous materials and equipment on site”.

Practical implications – The resulting implication for practice of these results can be summarised by identifying that with sustained development of urban centres on a global scale, coupled with the increasing complexity of architectural designs, the majority of on-site project management professionals are faced with the onerous task of completing often intricate designs within a limited spatial environment, under strict health and safety parameters.

Originality/value – The subsequent value of the findings are such that just as on-site management professionals successfully identify the various managerial issues highlighted, the successful management of health and safety on a confined construction site is attainable.

Heritability of the spatial distribution and peak density of macular pigment:a classical twin study

Purpose: To elucidate the heritability of peak density and spatial width of macular pigment (MP) using a Classical Twin Study.

Methods: Fundus autofluorescence images were obtained at 488?nm from 86 subjects or 43 twin pairs (21 monozygotic (MZ) and 22 dizygotic (DZ)) (27 male, 59 female) aged from 55 to 76 years (mean 62.2±5.3 years). The relative topographic distribution of MP was measured using a grey scale of intensity (0-255 units) in a 7° eccentricity around the fovea. Relative peak MP density (rPMPD) and relative spatial distribution of MP (rSDMP) were used as the main outcome measure in the statistical analysis.

Results: A significantly higher correlation was found within MZ pairs as compared with that within DZ pairs for rPMPD, (r=0.99, 95% confidence interval (95% CI) 0.93 to 1.00) and 0.22, 95% CI -0.34 to 0.71), respectively, suggesting strong heritability of this trait. When rSDMP was compared, there was no significant difference between the correlations within MZ pairs (r=0.48, 95% CI -0.02 to 0.83) and DZ pairs (r=0.63, 95% CI 0.32 to 0.83), thus rSDMP is unlikely to have a considerable heritable component. In addition, there was no difference between any MP parameter when normal maculae were compared with early age-related macular degeneration (AMD) (rPMPD 0.36 vs 0.34, t=1.18 P=0.243, rSDMP 1.75 vs 1.75, t=0.028 P=0.977).ConclusionsrPMPD is a strongly heritable trait whereas rSDMP has minimal genetic influence and a greater influence by environmental factors. The presence of macular changes associated with early AMD did not appear to influence any of these pigment parameters. © 2012 Macmillan Publishers Limited All rights reserved 0950-222X/12

Spatial and temporal ecology of Scots pine ectomycorrhizas

Spatial analysis was used to explore the distribution of individual species in an ectomycorrhizal (ECM) fungal community to address: whether mycorrhizas of individual ECM fungal species were patchily distributed, and at what scale; and what the causes of this patchiness might be. Ectomycorrhizas were extracted from spatially explicit samples of the surface organic horizons of a pine plantation. The number of mycorrhizas of each ECM fungal species was recorded using morphotyping combined with internal transcribed spacer (ITS) sequencing. Semivariograms, kriging and cluster analyses were used to determine both the extent and scale of spatial autocorrelation in species abundances, potential interactions between species, and change over time. The mycorrhizas of some, but not all, ECM fungal species were patchily distributed and the size of patches differed between species. The relative abundance of individual ECM fungal species and the position of patches of ectomycorrhizas changed between years. Spatial and temporal analysis revealed a dynamic ECM fungal community with many interspecific interactions taking place, despite the homogeneity of the host community. The spatial pattern of mycorrhizas was influenced by the underlying distribution of fine roots, but local root density was in turn influenced by the presence of specific fungal species.

Dietary fat and breast cancer survival: a systematic review and meta-analysis

As the number of breast cancer survivors increases worldwide(1), there is growing interest in the potential effect of dietary and lifestyle behaviours on overall prognosis. This is especially important as a cancer diagnosis is often referred to as a ‘teachable moment’(2) as patients seek information about lifestyle behaviours and so provision of evidence-based guidelines is essential. A positive association between dietary fat and breast cancer risk has been previously reported(3) but its influence upon breast cancer survival is unclear. The aim of this review and meta-analysis is to critically appraise the literature published to date and to conduct meta-analyses to pool the results of studies to clarify the association between dietary fat and breast cancer survival.
Relevant articles published up to March 2011 that examined dietary fat and breast cancer recurrence and survival were identified from searches in MEDLINE and EMBASE. Meta-analyses were conducted in which we evaluated the risk of all-cause or breast cancer death in women in the highest compared with the lowest categories of total fat intake (g/d) and per 20 g increase in intake of dietary fat. Multivariable adjusted relative risks (RR) and 95% CI from individual studies were weighted and combined using a random-effects model to produce a pooled estimate.
Twelve prospective cohort studies that investigated total fat intake (g) and breast cancer survival, and/or provided information on fat intake from which a linear trend could be estimated, were included in the analyses. There was no evidence of a difference in risk of breast cancer death (RR=1.14; 95% CI 0.86, 1.52; P=0.34) or all cause death (RR=1.73; 95% CI 0.82, 3.6; P=0.15) between the highest and lowest categories of total fat intake. Similarly, no significant difference in risk of breast cancer death (RR=1.03; 95% CI 0.97, 1.10; P=0.261) or all-cause death (RR=1.06; 95% CI 0.88, 1.28; P=0.52) was found per linear (20 g) increase in total fat intake.
The results of this systematic review and meta-analysis do not support an association between total dietary fat and breast cancer survival. Further investigation into the effect of specific types of dietary fat and breast cancer survival is of interest.

Numerical analysis of stiffener runout sections

The recent trend of incorporating more composite material in primary aircraft structures has highlighted the vulnerability of stiffened aerostructures to through-thickness stresses, which may lead to delamination and debonding at the skin-stiffener interface, leading to collapse. Stiffener runout regions are particularly susceptible to this problem and cannot be avoided due to the necessity to terminate stiffeners at rib intersections or at cutouts, interrupting the stiffener load path. In this paper, experimental tests relating to two different stiffener runout specimens are presented and the failure modes of both specimens are discussed in detail. A thinner-skinned specimen showed sudden and unstable crack propagation, while a thicker-skinned specimen showed initially unstable but subsequent stable crack growth. Detailed finite element models of the two specimens are developed, and it is shown how such models can explain and predict the behaviour and failure mode of stiffener runouts. The models contain continuum shell elements to model the skin and stiffener, while cohesive elements using a traction-separation law are placed at the skin-stiffener interface to effectively model the debonding which promotes structural failure.

A review of spatial and temporal variation in grey and common seal diet in the United Kingdom and Ireland

Knowledge about the diet of fish-eating predators is critical when evaluating conflicts with the fishing industry. Numerous primary studies have examined the diet of grey seals Halichoerus grypus and common seals Phoca vitulina in a bid to understand the ecology of these predators. However, studies of large-scale spatial and temporal variation in seal diet are limited. Therefore this review combines the results of seal diet studies published between 1980 and 2000 to examine how seal diet varies at a range of spatial and temporal scales. Our results revealed extensive spatial variation in gadiform, perciform and flatfish consumption, likely reflecting variation in prey availability. Flatfish and gadiform consumption varied between years, reflecting changes in fish assemblages as a consequence of factors such as varying fishing pressures, climate change and natural fluctuations in populations. Perciform and gadiform consumption varied seasonally: in addition there was a significant interaction between season and seal species, indicating that grey and common seals exhibited different patterns of seasonal variation in their consumption of Perciformes and Gadiformes. Multivariate analysis of grey seal diet revealed spatial variation at a much smaller scale, with different species dominating the diet in different areas. The existence of spatial and temporal variation in seal diet emphasizes that future assessments of the impact of seal populations should not be based on past or localized estimates of diet and highlights the need for up-to-date, site specific estimates of diet composition in the context of understanding and resolving seal/fisheries conflict. © 2012 Marine Biological Association of the United Kingdom.

Correlation analysis as a tool to investigate the bioaccessibility of nickel, vanadium and zinc in Northern Ireland soils

Correlation analyses were conducted on nickel (Ni), vanadium (V) and zinc (Zn) oral bioaccessible fractions (BAFs) and selected geochemistry parameters to identify specific controls exerted over trace element bioaccessibility. BAFs were determined by previous research using the unified BARGE method. Total trace element concentrations and soil geochemical parameters were analysed as part of the Geological Survey of Northern Ireland Tellus Project. Correlation analysis included Ni, V and Zn BAFs against their total concentrations, pH, estimated soil organic carbon (SOC) and a further eight element oxides. BAF data were divided into three separate generic bedrock classifications of basalt, lithic arenite and mudstone prior to analysis, resulting in an increase in average correlation coefficients between BAFs and geochemical parameters. Sulphur trioxide and SOC, spatially correlated with upland peat soils, exhibited significant positive correlations with all BAFs in gastric and gastro-intestinal digestion phases, with such effects being strongest in the lithic arenite bedrock group. Significant negative relationships with bioaccessible Ni, V and Zn and their associated total concentrations were observed for the basalt group. Major element oxides were associated with reduced oral trace element bioaccessibility, with Al2O3 resulting in the highest number of significant negative correlations followed by Fe2O3. spatial mapping showed that metal oxides were present at reduced levels in peat soils. The findings illustrate how specific geology and soil geochemistry exert controls over trace element bioaccessibility, with soil chemical factors having a stronger influence on BAF results than relative geogenic abundance. In general, higher Ni, V and Zn bioaccessibility is expected in peat soil types.

JISC Workshop Report: E-Research Resources, Tools and Methods for Historic Place Name Analysis

A substantial amount of the 'critical mass' of digital data available to scholarship contains place-names, and it is now recognised that spatial and temporal data points, including place-names, are a vital part of the e-research infrastructure that supports the use, re-use and advanced analysis of data using ICT tools and methods. Place-names can also be linked semantically to contribute to the web of data, and to enrich content through linking existing data, and identifying new collections for digitization to strategically enhance existing digital collections. However, existing e-projects rely on modern gazetteers limiting them to the modern and the near-contemporary. This workshop explored how to further integrate the wealth of historical place-name scholarship, and the resulting digital resources generated within UK academia, so enabling integration of local knowledge over much longer periods.