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

Quark Contributions to Nucleon Momentum and Spin from Domain Wall fermion calculations

We report contributions to the nucleon spin and momentum from light quarks calculated using dynamical domain wall fermions with pion masses down to 300 MeV and fine lattice spacing a=0.084 fm. Albeit without disconnected diagrams, we observe that spin and orbital angular momenta of both u and d quarks are opposite, almost canceling in the case of the d quark, which agrees with previous calculations using a mixed quark action. We also present the full momentum dependence of n=2 generalized form factors showing little variation with the pion mass.Comment: 7 pages, 5 figures, NT-LBNL-11-020, MIT-CTP-4323. Presented at the 29th International Symposium on Lattice Field Theory (Lattice 2011), Squaw Valley, California, 10-16 Jul 201

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

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

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

Combining behavioural activation with physical activity promotion for adults with depression: findings of a parallel-group pilot randomised controlled trial (BAcPAc)

BACKGROUND: Depression is associated with physical inactivity, which may mediate the relationship between depression and a range of chronic physical health conditions. However, few interventions have combined a psychological intervention for depression with behaviour change techniques, such as behavioural activation (BA), to promote increased physical activity. METHODS: To determine procedural and clinical uncertainties to inform a definitive randomised controlled trial (RCT), a pilot parallel-group RCT was undertaken within two Improving Access to Psychological Therapies (IAPT) services in South West England. We aimed to recruit 80 adults with depression and randomise them to a supported, written self-help programme based on either BA or BA plus physical activity promotion (BAcPAc). Data were collected at baseline and 4 months post-randomisation to evaluate trial retention, intervention uptake and variance in outcomes to inform a sample size calculation. Qualitative data were collected from participants and psychological wellbeing practitioners (PWPs) to assess the acceptability and feasibility of the trial methods and the intervention. Routine data were collected to evaluate resource use and cost. RESULTS: Sixty people with depression were recruited, and a 73 % follow-up rate was achieved. Accelerometer physical activity data were collected for 64 % of those followed. Twenty participants (33 %) attended at least one treatment appointment. Interview data were analysed for 15 participants and 9 study PWPs. The study highlighted the challenges of conducting an RCT within existing IAPT services with high staff turnover and absences, participant scheduling issues, PWP and participant preferences for cognitive focussed treatment, and deviations from BA delivery protocols. The BAcPAc intervention was generally acceptable to patients and PWPs. CONCLUSIONS: Although recruitment procedures and data collection were challenging, participants generally engaged with the BAcPAc self-help booklets and reported willingness to increase their physical activity. A number of feasibility issues were identified, in particular the under-use of BA as a treatment for depression, the difficulty that PWPs had in adapting their existing procedures for study purposes and the instability of the IAPT PWP workforce. These problems would need to be better understood and resolved before proceeding to a full-scale RCT. TRIAL REGISTRATION: ISRCTN74390532 . Registered on 26 March 2013

Matrix Regularization of an Open Supermembrane ---towards M-theory five-branes via open supermembranes ---

We study open supermembranes in 11 dimensional rigid superspace with 6 dimensional topological defects (M-theory five-branes). After rederiving in the Green-Schwarz formalism the boundary conditions for open superstrings in the type IIA theory, we determine the boundary conditions for open supermembranes by imposing kappa symmetry and invariance under a fraction of 11 dimensional supersymmetry. The result seems to imply the self-duality of the three-form field strength on the five-brane world volume. We show that the light-cone gauge formulation is regularized by a dimensional reduction of a 6 dimensional N=1 super Yang-Mills theory with the gauge group SO(N\to\infty). We also analyze the SUSY algebra and BPS states in the light-cone gauge.Comment: 30 pages, Latex, references and Appendix E added, some minor changes mad

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