Rare charm meson decays D->Pl^+l^- and c->ul^+l^- in SM and MSSM

We study the nine possible rare charm meson decays D->Pl^+l^- (P=pi,K,eta,eta') using the Heavy Meson Chiral Lagrangians and find them to be dominated by the long distance contributions. The decay D^+ -> pi^+l^+l^- with the branching ratio 1*10^(-6) is expected to have the best chances for an early experimental discovery. The short distance contribution in the five Cabibbo suppressed channels arises via the c->ul^+l^- transition; we find that this contribution is detectable only in the D->pi l^+l^- decay, where it dominates the differential spectrum at high-q^2. The general Minimal Supersymmetric Standard Model can enhance the c->ul^+l^- rate by up to an order of magnitude; its effect on the D->Pl^+l^- rates is small since the c->ul^+l^- enhancement is sizable in low-q^2 region, which is inhibited in the hadronic decay.Comment: 17 page

Energy Flow in the Hadronic Final State of Diffractive and Non-Diffractive Deep-Inelastic Scattering at HERA

An investigation of the hadronic final state in diffractive and non--diffractive deep--inelastic electron--proton scattering at HERA is presented, where diffractive data are selected experimentally by demanding a large gap in pseudo --rapidity around the proton remnant direction. The transverse energy flow in the hadronic final state is evaluated using a set of estimators which quantify topological properties. Using available Monte Carlo QCD calculations, it is demonstrated that the final state in diffractive DIS exhibits the features expected if the interaction is interpreted as the scattering of an electron off a current quark with associated effects of perturbative QCD. A model in which deep--inelastic diffraction is taken to be the exchange of a pomeron with partonic structure is found to reproduce the measurements well. Models for deep--inelastic $ep$ scattering, in which a sizeable diffractive contribution is present because of non--perturbative effects in the production of the hadronic final state, reproduce the general tendencies of the data but in all give a worse description.Comment: 22 pages, latex, 6 Figures appended as uuencoded fil

A Search for Selectrons and Squarks at HERA

Data from electron-proton collisions at a center-of-mass energy of 300 GeV are used for a search for selectrons and squarks within the framework of the minimal supersymmetric model. The decays of selectrons and squarks into the lightest supersymmetric particle lead to final states with an electron and hadrons accompanied by large missing energy and transverse momentum. No signal is found and new bounds on the existence of these particles are derived. At 95% confidence level the excluded region extends to 65 GeV for selectron and squark masses, and to 40 GeV for the mass of the lightest supersymmetric particle.Comment: 13 pages, latex, 6 Figure

Dynamic contrast-enhanced CT compared with positron emission tomography CT to characterise solitary pulmonary nodules : the SPUtNIk diagnostic accuracy study and economic modelling

Background Current pathways recommend positron emission tomography–computerised tomography for the characterisation of solitary pulmonary nodules. Dynamic contrast-enhanced computerised tomography may be a more cost-effective approach. Objectives To determine the diagnostic performances of dynamic contrast-enhanced computerised tomography and positron emission tomography–computerised tomography in the NHS for solitary pulmonary nodules. Systematic reviews and a health economic evaluation contributed to the decision-analytic modelling to assess the likely costs and health outcomes resulting from incorporation of dynamic contrast-enhanced computerised tomography into management strategies. Design Multicentre comparative accuracy trial. Setting Secondary or tertiary outpatient settings at 16 hospitals in the UK. Participants Participants with solitary pulmonary nodules of ≥ 8 mm and of ≤ 30 mm in size with no malignancy in the previous 2 years were included. Interventions Baseline positron emission tomography–computerised tomography and dynamic contrast-enhanced computer tomography with 2 years’ follow-up. Main outcome measures Primary outcome measures were sensitivity, specificity and diagnostic accuracy for positron emission tomography–computerised tomography and dynamic contrast-enhanced computerised tomography. Incremental cost-effectiveness ratios compared management strategies that used dynamic contrast-enhanced computerised tomography with management strategies that did not use dynamic contrast-enhanced computerised tomography. Results A total of 380 patients were recruited (median age 69 years). Of 312 patients with matched dynamic contrast-enhanced computer tomography and positron emission tomography–computerised tomography examinations, 191 (61%) were cancer patients. The sensitivity, specificity and diagnostic accuracy for positron emission tomography–computerised tomography and dynamic contrast-enhanced computer tomography were 72.8% (95% confidence interval 66.1% to 78.6%), 81.8% (95% confidence interval 74.0% to 87.7%), 76.3% (95% confidence interval 71.3% to 80.7%) and 95.3% (95% confidence interval 91.3% to 97.5%), 29.8% (95% confidence interval 22.3% to 38.4%) and 69.9% (95% confidence interval 64.6% to 74.7%), respectively. Exploratory modelling showed that maximum standardised uptake values had the best diagnostic accuracy, with an area under the curve of 0.87, which increased to 0.90 if combined with dynamic contrast-enhanced computerised tomography peak enhancement. The economic analysis showed that, over 24 months, dynamic contrast-enhanced computerised tomography was less costly (£3305, 95% confidence interval £2952 to £3746) than positron emission tomography–computerised tomography (£4013, 95% confidence interval £3673 to £4498) or a strategy combining the two tests (£4058, 95% confidence interval £3702 to £4547). Positron emission tomography–computerised tomography led to more patients with malignant nodules being correctly managed, 0.44 on average (95% confidence interval 0.39 to 0.49), compared with 0.40 (95% confidence interval 0.35 to 0.45); using both tests further increased this (0.47, 95% confidence interval 0.42 to 0.51). Limitations The high prevalence of malignancy in nodules observed in this trial, compared with that observed in nodules identified within screening programmes, limits the generalisation of the current results to nodules identified by screening. Conclusions Findings from this research indicate that positron emission tomography–computerised tomography is more accurate than dynamic contrast-enhanced computerised tomography for the characterisation of solitary pulmonary nodules. A combination of maximum standardised uptake value and peak enhancement had the highest accuracy with a small increase in costs. Findings from this research also indicate that a combined positron emission tomography–dynamic contrast-enhanced computerised tomography approach with a slightly higher willingness to pay to avoid missing small cancers or to avoid a ‘watch and wait’ policy may be an approach to consider. Future work Integration of the dynamic contrast-enhanced component into the positron emission tomography–computerised tomography examination and the feasibility of dynamic contrast-enhanced computerised tomography at lung screening for the characterisation of solitary pulmonary nodules should be explored, together with a lower radiation dose protocol. Study registration This study is registered as PROSPERO CRD42018112215 and CRD42019124299, and the trial is registered as ISRCTN30784948 and ClinicalTrials.gov NCT02013063

Comparative Accuracy and Cost-Effectiveness of Dynamic Contrast Enhanced Computed Tomography and Positron Emission Tomography in the Characterisation of Solitary Pulmonary Nodules

Abstract Introduction: Dynamic contrast-enhanced computed tomography (DCE-CT) and Positron Emission Tomography/Computed Tomography (PET/CT) have a high reported accuracy for the diagnosis of malignancy in solitary pulmonary nodules. The aim of this study was to compare the accuracy and cost-effectiveness of these. Methods: In this prospective multicentre trial, 380 participants with a solitary pulmonary nodule (8-30mm) and no recent history of malignancy underwent DCE-CT and PET/CT. All patients underwent either biopsy with histological diagnosis or completed CT follow-up. Primary outcome measures were sensitivity, specificity, and overall diagnostic accuracy for PET/CT and DCE-CT. Costs and cost-effectiveness were estimated from a healthcare provider perspective using a decision-model. Results: 312 participants (47% female, 68.1±9.0 years) completed the study, with 61% rate of malignancy at 2 years. The sensitivity, specificity, positive predictive value and negative predictive values for DCE-CT were 95.3% [95% CI 91.3;97.5], 29.8% [95% CI 22.3;38.4], 68.2% [95% CI 62.4%;73.5%] and 80.0% [95% CI 66.2;89.1] respectively, and for PET/CT were 79.1% [95% CI 72.7;84.2], 81.8% [95% CI 74.0;87.7], 87.3%[95% CI 81.5;91.5) and 71·2% [95% CI 63.2;78.1]. The area under the receiver operator characteristic curve (AUROC) for DCE-CT and PET/CT was 0.62 [95%CI 0.58;0.67] and 0.80 [95%CI 0.76;0.85] respectively (p<0.001). Combined results significantly increased diagnostic accuracy over PET/CT alone (AUROC=0.90 [95%CI 0.86;0.93], p<0.001). DCE-CT was preferred when the willingness to pay per incremental cost per correctly treated malignancy was below £9000. Above £15500 a combined approach was preferred. Conclusions: PET/CT has a superior diagnostic accuracy to DCE-CT for the diagnosis of solitary pulmonary nodules. Combining both techniques improves the diagnostic accuracy over either test alone and could be cost-effective. (Clinical trials.gov - NCT02013063)

A Measurement of the Proton Structure Function F ⁣2(x,Q2)F_{\!2}(x,Q^2)

A measurement of the proton structure function $F_{\!2}(x,Q^2)$ is reported for momentum transfer squared $Q^2$ between 4.5 $GeV^2$ and 1600 $GeV^2$ and for Bjorken $x$ between $1.8\cdot10^{-4}$ and 0.13 using data collected by the HERA experiment H1 in 1993. It is observed that $F_{\!2}$ increases significantly with decreasing $x$, confirming our previous measurement made with one tenth of the data available in this analysis. The $Q^2$ dependence is approximately logarithmic over the full kinematic range covered. The subsample of deep inelastic events with a large pseudo-rapidity gap in the hadronic energy flow close to the proton remnant is used to measure the "diffractive" contribution to $F_{\!2}$.Comment: 32 pages, ps, appended as compressed, uuencoded fil

The Influence of Age and Sex on Genetic Associations with Adult Body Size and Shape : A Large-Scale Genome-Wide Interaction Study

Genome-wide association studies (GWAS) have identified more than 100 genetic variants contributing to BMI, a measure of body size, or waist-to-hip ratio (adjusted for BMI, WHRadjBMI), a measure of body shape. Body size and shape change as people grow older and these changes differ substantially between men and women. To systematically screen for age-and/or sex-specific effects of genetic variants on BMI and WHRadjBMI, we performed meta-analyses of 114 studies (up to 320,485 individuals of European descent) with genome-wide chip and/or Metabochip data by the Genetic Investigation of Anthropometric Traits (GIANT) Consortium. Each study tested the association of up to similar to 2.8M SNPs with BMI and WHRadjBMI in four strata (men 50y, women 50y) and summary statistics were combined in stratum-specific meta-analyses. We then screened for variants that showed age-specific effects (G x AGE), sex-specific effects (G x SEX) or age-specific effects that differed between men and women (G x AGE x SEX). For BMI, we identified 15 loci (11 previously established for main effects, four novel) that showed significant (FDR= 50y). No sex-dependent effects were identified for BMI. For WHRadjBMI, we identified 44 loci (27 previously established for main effects, 17 novel) with sex-specific effects, of which 28 showed larger effects in women than in men, five showed larger effects in men than in women, and 11 showed opposite effects between sexes. No age-dependent effects were identified for WHRadjBMI. This is the first genome-wide interaction meta-analysis to report convincing evidence of age-dependent genetic effects on BMI. In addition, we confirm the sex-specificity of genetic effects on WHRadjBMI. These results may providefurther insights into the biology that underlies weight change with age or the sexually dimorphism of body shape.Peer reviewe