A general framework for quantifying the effects of DNA repair inhibitors on radiation sensitivity as a function of dose

Purpose. Current methods for quantifying effects of DNA repair modifiers on radiation sensitivity assume a constant effect independent of the radiation dose received. The aim of this study was to develop and evaluate a modelling strategy by which radiation dose dependent effects of DNA repair inhibitors on clonogenic survival might be identified and their significance assessed. Methods. An indicator model that allowed quantification of the Sensitiser Effect on Radiation response as a function of Dose (SERD) was developed. This model was fitted to clonogenic survival data derived from human tumour and rodent fibroblast cell lines irradiated in the presence and absence of chemical inhibitors of poly(ADP-ribose) polymerase (PARP) activity. Results. PARP inhibition affected radiation response in a cell cycle and radiation dose dependent manner, and was also associated with significant radiation-independent effects on clonogenic survival. Application of the SERD method enabled identification of components of the radiation response that were significantly affected by PARP inhibition and indicated the magnitude of the effects on each component. Conclusion. The proposed approach improves on current methods of analysing effects of DNA repair modification on radiation response. Furthermore, it may be generalised to account for other parameters such as proliferation or dose rate to enable its use in the context of fractionated or continuous radiation exposures

VisGenome: visualization of single and comparative genome representations

VisGenome visualizes single and comparative representations for the rat, the mouse and the human chromosomes at different levels of detail. The tool offers smooth zooming and panning which is more flexible than seen in other browsers. It presents information available in Ensembl for single chromosomes, as well as homologies (orthologue predictions including ortholog one2one, apparent ortholog one2one, ortholog many2many) for any two chromosomes from different species. The application can query supporting data from Ensembl by invoking a link in a browser

Sporadic Human Cryptosporidiosis Caused by Cryptosporidium cuniculus, United Kingdom, 2007–2008

To investigate sporadic human cryptosporidiosis trends in the United Kingdom, we tested 3,030 Cryptosporidium spp.–positive fecal samples, submitted for routine typing in 2007–2008, for C. cuniculus. C. cuniculus prevalence was 1.2%; cases were mostly indigenous and occurred across all age groups. Most occurred during August–October and may be linked to exposure opportunities

National survey of the prevalence, incidence, primary care burden, and treatment of heart failure in Scotland

Objective: To examine the epidemiology, primary care burden, and treatment of heart failure in Scotland, UK. Design: Cross sectional data from primary care practices participating in the Scottish continuous morbidity recording scheme between 1 April 1999 and 31 March 2000. Setting: 53 primary care practices (307 741 patients). Subjects: 2186 adult patients with heart failure. Results: The prevalence of heart failure in Scotland was 7.1 in 1000, increasing with age to 90.1 in 1000 among patients 85 years. The incidence of heart failure was 2.0 in 1000, increasing with age to 22.4 in 1000 among patients 85 years. For older patients, consultation rates for heart failure equalled or exceeded those for angina and hypertension. Respiratory tract infection was the most common co-morbidity leading to consultation. Among men, 23% were prescribed a ß blocker, 11% spironolactone, and 46% an angiotensin converting enzyme inhibitor. The corresponding figures for women were 20% (p = 0.29 versus men), 7% (p = 0.02), and 34% (p < 0.001). Among patients < 75 years 26% were prescribed a β blocker, 11% spironolactone, and 50% an angiotensin converting enzyme inhibitor. The corresponding figures for patients 75 years were 19% (p = 0.04 versus patients < 75), 7% (p = 0.04), and 33% (p < 0.001). Conclusions: Heart failure is a common condition, especially with advancing age. In the elderly, the community burden of heart failure is at least as great as that of angina or hypertension. The high rate of concomitant respiratory tract infection emphasises the need for strategies to immunise patients with heart failure against influenza and pneumococcal infection. Drugs proven to improve survival in heart failure are used less frequently for elderly patients and women

Sharing the Burden of Collective Security in the European Union. Research Note

This article compares European Union (EU) burden-sharing in security governance distinguishing between assurance, prevention, protection, and compellence policies. We employ joint-product models and examine the variation in the level of publicness, the asymmetry of the distribution of costs and benefits, and aggregation technologies in each policy domain. Joint-product models predict equal burden sharing for protection and assurance because of their respective weakest-link and summation aggregation technologies with symmetric costs. Prevention is also characterized by the technology of summation, but asymmetry of costs implies uneven burden-sharing. Uneven burden-sharing is predicted for compellence because it has the largest asymmetry of costs and a best-shot aggregation technology. Evaluating burden-sharing relative to a country?s ability to contribute, Kendall tau-tests examine the rank-correlation between security burden and the capacity of EU member states. These tests show that the smaller EU members disproportionately shoulder the costs of assurance and protection; wealthier EU members carry a somewhat disproportionate burden in the provision of prevention, and larger EU members in the provision of compellence. When analyzing contributions relative to expected benefits, asymmetric marginal costs can largely explain uneven burden-sharing. The main conclusion is that the aggregated burden of collective security governance in the EU is shared quite evenly

Modelling the evaporation of nanoparticle suspensions from heterogeneous surfaces

We present a Monte Carlo (MC) grid-based model for the drying of drops of a nanoparticle suspension upon a heterogeneous surface. The model consists of a generalised lattice-gas in which the interaction parameters in the Hamiltonian can be varied to model different properties of the materials involved. We show how to choose correctly the interactions, to minimise the effects of the underlying grid so that hemispherical droplets form. We also include the effects of surface roughness to examine the effects of contact-line pinning on the dynamics. When there is a `lid' above the system, which prevents evaporation, equilibrium drops form on the surface, which we use to determine the contact angle and how it varies as the parameters of the model are changed. This enables us to relate the interaction parameters to the materials used in applications. The model has also been applied to drying on heterogeneous surfaces, in particular to the case where the suspension is deposited on a surface consisting of a pair of hydrophilic conducting metal surfaces that are either side of a band of hydrophobic insulating polymer. This situation occurs when using inkjet printing to manufacture electrical connections between the metallic parts of the surface. The process is not always without problems, since the liquid can dewet from the hydrophobic part of the surface, breaking the bridge before the drying process is complete. The MC model reproduces the observed dewetting, allowing the parameters to be varied so that the conditions for the best connection can be established. We show that if the hydrophobic portion of the surface is located at a step below the height of the neighbouring metal, the chance of dewetting of the liquid during the drying process is significantly reduced.Comment: 14 pages, 14 figure

Integrated urgent care / NHS 111 workforce blueprint: workforce governance guide

This guide outlines the governance, both formal and informal, that will support the Integrated Urgent Care (IUC) / NHS 111 workforce to continue to deliver excellent frontline care to the public. It includes recommendations on appraisal, revalidation, supervision, and using audit to support these. In response to engagement exercises, it also touches on governance around recruitment, reducing attrition and on the physical environment that team members work in

Simplifying Algebra in Feynman Graphs, Part III: Massive Vectors

A T-dualized selfdual inspired formulation of massive vector fields coupled to arbitrary matter is generated; subsequently its perturbative series modeling a spontaneously broken gauge theory is analyzed. The new Feynman rules and external line factors are chirally minimized in the sense that only one type of spin index occurs in the rules. Several processes are examined in detail and the cross-sections formulated in this approach. A double line formulation of the Lorentz algebra for Feynman diagrams is produced in this formalism, similar to color ordering, which follows from a spin ordering of the Feynman rules. The new double line formalism leads to further minimization of gauge invariant scattering in perturbation theory. The dualized electroweak model is also generated.Comment: 39 pages, LaTeX, 8 figure