A novel splice variant of the DNA-PKcs gene is associated with clinical and cellular radiosensitvity in a xeroderma pigmentosum patient

This article has been made available through the Brunel Open Access Publishing Fund.Background: Radiotherapy-induced DNA double strand breaks (DSB) are critical cytotoxic lesions. Inherited defects in DSB DNA repair pathways lead to hypersensitivity to ionising radiation, immunodeficiency and increased cancer incidence. A patient with xeroderma pigmentosum complementation group C, with a scalp angiosarcoma exhibited dramatic clinical radiosensitivity following radiotherapy, resulting in death. A fibroblast cell line from non-affected skin (XP14BRneo17) was hypersensitive to ionising radiation and defective in DNA double strand break repair. Aim: To determine the genetic defect causing cellular radiation hypersensitivity in XP14BRneo17 cells. Methods: Functional genetic complementation whereby copies of human chromosomes containing genes involved in DNA DSB repair (chromosomes 2, 5, 8 10, 13 and 22) were individually transferred to XP14BRneo17 cells in an attempt to correct the radiation hypersensitivity. Clonogenic survival assays and γ-H2AX immunofluorescence were conducted to measure radiation sensitivity and repair of DNA DSBs. DNA sequencing of defective DNA repair genes was performed. Results: Transfer of chromosome 8 (location of DNA-PKcs gene), and transfection of a mammalian expression construct containing the DNA-PKcs cDNA restored normal ionising radiation sensitivity and repair of DNA DSBs in XP14BRneo17 cells. DNA sequencing of the DNA-PKcs coding region revealed a 249 bp deletion (between base pairs 3656-3904) encompassing exon 31 of the gene. Conclusion: We provide evidence of a novel splice variant of the DNA-PKcs gene associated with radiosensitivity in a xeroderma pigmentosum patient and report the first double mutant in distinct DNA repair pathways being consistent with viability.Brunel Open Access Publishing Fun

Decays of metastable vacua in SQCD

The decay rates of metastable SQCD vacua in ISS-type models, both towards supersymmetric vacua as well as towards other nonsupersymmetric configurations arising in theories with elementary spectators, are estimated numerically in the semiclassical approximation by computing the corresponding multifield bounce configurations. The scaling of the bounce action with respect to the most relevant dimensionless couplings and ratios of scales is analyzed. In the case of the decays towards the susy vacua generated by nonperturbative effects, the results confirm previous analytical estimations of this scaling, obtained by assuming a triangular potential barrier. The decay rates towards susy vacua generated by R-symmetry breaking interactions turn out to be more than sufficiently suppressed for the phenomenologically relevant parameter range, and their behavior in this regime differs from analytic estimations valid for parametrically small scale ratios. It is also shown that in models with spectator fields, even though the decays towards vacua involving nonzero spectator VEVs don't have a strong parametric dependence on the scale ratios, the ISS vacuum can still be made long-lived in the presence of R-symmetry breaking interactions.Comment: 22 pages, 7 figure

Decision for reconstructive interventions of the upper limb in individuals with tetraplegia: the effect of treatment characteristics

Objective: To determine the effect of treatment characteristics on the\ud decision for reconstructive interventions for the upper extremities (UE) in\ud subjects with tetraplegia. - \ud Setting: Seven specialized spinal cord injury centres in the Netherlands. - \ud Method: Treatment characteristics for UE reconstructive interventions were\ud determined. Conjoint analysis (CA) was used to determine the contribution\ud and the relative importance of the treatment characteristics on the decision\ud for therapy. Therefore, a number of different treatment scenarios using these\ud characteristics were established. Different pairs of scenarios were presented\ud to subjects who were asked to choose the preferred scenario of each set. - \ud Results: forty nine subjects with tetraplegia with a stable C5, C6 or C7\ud lesion were selected. All treatment characteristics significantly influenced\ud the choice for treatment. Relative importance of treatment characteristics\ud were: intervention type (surgery or surgery with FES implant) 13%, number\ud of operations 15%, in patient rehabilitation period 22%, ambulant\ud rehabilitation period 9%, complication rate 15%, improvement of elbow\ud function 10%, improvement of hand function 15%. In deciding for therapy\ud 40% of the subjects focused on one characteristic. - \ud Conclusion: CA is applicable in Spinal Cord Injury medicine to study the\ud effect of health outcomes and non-health outcomes on the decision for\ud treatment. Non-health outcomes which relate to the intensity of treatment\ud are equally important or even more important than functional outcome in the\ud decision for reconstructive UE surgery in subjects with tetraplegia

How does reviewing the evidence change veterinary surgeons' beliefs regarding the treatment of ovine footrot? A quantitative and qualitative study

Footrot is a widespread, infectious cause of lameness in sheep, with major economic and welfare costs. The aims of this research were: (i) to quantify how veterinary surgeons’ beliefs regarding the efficacy of two treatments for footrot changed following a review of the evidence (ii) to obtain a consensus opinion following group discussions (iii) to capture complementary qualitative data to place their beliefs within a broader clinical context. Grounded in a Bayesian statistical framework, probabilistic elicitation (roulette method) was used to quantify the beliefs of eleven veterinary surgeons during two one-day workshops. There was considerable heterogeneity in veterinary surgeons’ beliefs before they listened to a review of the evidence. After hearing the evidence, seven participants quantifiably changed their beliefs. In particular, two participants who initially believed that foot trimming with topical oxytetracycline was the better treatment, changed to entirely favour systemic and topical oxytetracycline instead. The results suggest that a substantial amount of the variation in beliefs related to differences in veterinary surgeons’ knowledge of the evidence. Although considerable differences in opinion still remained after the evidence review, with several participants having non-overlapping 95% credible intervals, both groups did achieve a consensus opinion. Two key findings from the qualitative data were: (i) veterinary surgeons believed that farmers are unlikely to actively seek advice on lameness, suggesting a proactive veterinary approach is required (ii) more attention could be given to improving the way in which veterinary advice is delivered to farmers. In summary this study has: (i) demonstrated a practical method for probabilistically quantifying how veterinary surgeons’ beliefs change (ii) revealed that the evidence that currently exists is capable of changing veterinary opinion (iii) suggested that improved transfer of research knowledge into veterinary practice is needed (iv) identified some potential obstacles to the implementation of veterinary advice by farmers

The Matter and the Pseudoscalar Densities in Lattice QCD

The matter and the pseudoscalar densities inside a hadron are calculated via gauge-invariant equal-time correlation functions. A comparison is made between the charge charge and the matter density distributions for the pion, the rho, the nucleon and the $\Delta^+$ within the quenched theory, and with two flavours of dynamical quarks.Comment: Typos corrected; 13 pages, 16 figure

Towards an optimal design of target for tsetse control: comparisons of novel targets for the control of palpalis group tsetse in West Africa

Background: Tsetse flies of the Palpalis group are the main vectors of sleeping sickness in Africa. Insecticide impregnated targets are one of the most effective tools for control. However, the cost of these devices still represents a constraint to their wider use. The objective was therefore to improve the cost effectiveness of currently used devices. Methodology/Principal Findings: Experiments were performed on three tsetse species, namely Glossina palpalis gambiensis and G. tachinoides in Burkina Faso and G. p. palpalis in Côte d'Ivoire. The 1×1 m2 black blue black target commonly used in W. Africa was used as the standard, and effects of changes in target size, shape, and the use of netting instead of black cloth were measured. Regarding overall target shape, we observed that horizontal targets (i.e. wider than they were high) killed 1.6-5x more G. p. gambiensis and G. tachinoides than vertical ones (i.e. higher than they were wide) (P<0.001). For the three tsetse species including G. p. palpalis, catches were highly correlated with the size of the target. However, beyond the size of 0.75 m, there was no increase in catches. Replacing the black cloth of the target by netting was the most cost efficient for all three species. Conclusion/Significance: Reducing the size of the current 1*1 m black-blue-black target to horizontal designs of around 50 cm and replacing black cloth by netting will improve cost effectiveness six-fold for both G. p. gambiensis and G. tachinoides. Studying the visual responses of tsetse to different designs of target has allowed us to design more cost-effective devices for the effective control of sleeping sickness and animal trypanosomiasis in Africa

Submillimetre point sources from the Archeops experiment: Very Cold Clumps in the Galactic Plane

Archeops is a balloon-borne experiment, mainly designed to measure the Cosmic Microwave Background (CMB) temperature anisotropies at high angular resolution (~ 12 arcminutes). By-products of the mission are shallow sensitivity maps over a large fraction of the sky (about 30 %) in the millimetre and submillimetre range at 143, 217, 353 and 545 GHz. From these maps, we produce a catalog of bright submillimetre point sources. We present in this paper the processing and analysis of the Archeops point sources. Redundancy across detectors is the key factor allowing to sort out glitches from genuine point sources in the 20 independent maps. We look at the properties of the most reliable point sources, totalling 304. Fluxes range from 1 to 10,000 Jy (at the frequencies covering 143 to 545 GHz). All sources are either planets (2) or of galactic origin. Longitude range is from 75 to 198 degrees. Some of the sources are associated with well-known Lynds Nebulae and HII compact regions in the galactic plane. A large fraction of the sources have an IRAS counterpart. Except for Jupiter, Saturn, the Crab and Cas A, all sources show a dust-emission-like modified blackbody emission spectrum. Temperatures cover a range from 7 to 27 K. For the coldest sources (T<10 K), a steep nu^beta emissivity law is found with a surprising beta ~ 3 to 4. An inverse relationship between T and beta is observed. The number density of sources at 353 GHz with flux brighter than 100 Jy is of the order of 1 per degree of Galactic longitude. These sources will provide a strong check for the calibration of the Planck HFI focal plane geometry as a complement to planets. These very cold sources observed by Archeops should be prime targets for mapping observations by the Akari and Herschel space missions and ground--based observatories.Comment: Version matching the published article (English improved). Published in Astron. Astrophys, 21 pages, 13 figures, 4 tables Full article (with complete tables) can be retrieved at http://www.archeops.org/Archeops_Publicatio

Access to interpreting services in England: secondary analysis of national data

Background: Overcoming language barriers to health care is a global challenge. There is great linguistic diversity in the major cities in the UK with more than 300 languages, excluding dialects, spoken by children in London alone. However, there is dearth of data on the number of non-English speakers for planning effective interpreting services. The aim was to estimate the number of people requiring language support amongst the minority ethnic communities in England. Methods: Secondary analysis of national representative sample of subjects recruited to the Health Surveys for England 1999 and 2004. Results: 298,432 individuals from the four main minority ethnic communities (Indian, Pakistani, Bangladeshi and Chinese) who may be unable to communicate effectively with a health professional. This represents 2,520,885 general practice consultations per year where interpreting services might be required. Conclusion: Effective interpreting services are required to improve access and health outcomes of non-English speakers and thereby facilitate a reduction in health inequalities

Hypermatrix factors for string and membrane junctions

The adjoint representations of the Lie algebras of the classical groups SU(n), SO(n), and Sp(n) are, respectively, tensor, antisymmetric, and symmetric products of two vector spaces, and hence are matrix representations. We consider the analogous products of three vector spaces and study when they appear as summands in Lie algebra decompositions. The Z3-grading of the exceptional Lie algebras provide such summands and provides representations of classical groups on hypermatrices. The main natural application is a formal study of three-junctions of strings and membranes. Generalizations are also considered.Comment: 25 pages, 4 figures, presentation improved, minor correction