Cost-Effectiveness of Digital Breast Tomosynthesis vs. Abbreviated Breast MRI for Screening Women with Intermediate Risk of Breast Cancer—How Low-Cost Must MRI Be?

Background: Digital breast tomosynthesis (DBT) and abbreviated breast MRI (AB-MRI) offer superior diagnostic performance compared to conventional mammography in screening women with intermediate risk of breast cancer due to dense breast tissue. The aim of this model-based economic evaluation was to analyze whether AB-MRI is cost-effective in this cohort compared to DBT. Methods: Decision analysis and Markov simulations were used to model the cumulative costs and quality-adjusted life-years (QALYs) over a time horizon of 30 years. Model input parameters were adopted from recent literature. Deterministic and probabilistic sensitivity analyses were applied to test the stability of the model. Results: In the base-case scenario, the costs of an AB-MRI examination were defined to equal the costs of a full protocol acquisition. Two-yearly screening of women with dense breasts resulted in cumulative discounted costs of $8798 and$9505 for DBT and AB-MRI, and cumulative discounted effects of 19.23 and 19.27 QALYs, respectively, with an incremental cost-effectiveness ratio of $20,807 per QALY gained in the base-case scenario. By reducing the cost of an AB-MRI examination below a threshold of$241 in sensitivity analyses, AB-MRI would become cost-saving compared to DBT. Conclusion: In comparison to DBT, AB-MRI can be considered cost-effective up to a price per examination of $593 in screening patients at intermediate risk of breast cancer

Differentiation of ductal carcinoma in situ versus fibrocystic changes by magnetic resonance imaging: are there pathognomonic imaging features?

Background In breast magnetic resonance imaging (MRI), the diagnosis of ductal carcinoma in situ (DCIS) remains controversial; the most challenging cause of false-positive DCIS diagnosis is fibrocystic changes (FC). Purpose To search for typical and pathognomonic patterns of DCIS and FC using a standard clinical MRI protocol. Material and Methods Consecutive patients scheduled for breast MRI (standardized protocols @ 1.5T: dynamic-T1-GRE before/after Gd-DTPA [0.1 mmol/kg body weight (BW)]; T1-TSE), with subsequent pathological sampling, were investigated. Sixteen MRI descriptors were prospectively assessed by two experienced radiologists in consensus (blinded to pathology) and explored in patients with DCIS (n = 77) or FC (n = 219). Univariate and multivariate statistics were performed to identify the accuracy of descriptors (alone, combined). Furthermore, pathognomonic descriptor-combinations with an accuracy of 100% were explored (χ2 statistics; decision trees). Results Six breast MRI descriptors significantly differentiated DCIS from FC (Pcorrected < 0.05; odds ratio < 7.9). Pathognomonic imaging features were present in 33.8% (n = 100) of all cases allowing the identification of 42.9% of FC (n = 94). Conclusion Pathognomonic patterns of DCIS and FC were frequently observed in a standard clinical MRI protocol. Such imaging patterns could decrease the false-positive rate of breast MRI and hence might help to decrease the number of unnecessary biopsies in this clinically challenging subgroup

The Conformational Equilibrium of the Neuropeptide Y2 Receptor in Bilayer Membranes

Dynamic structural transitions within the seven-transmembrane bundle represent the mechanism by which G-protein-coupled receptors convert an extracellular chemical signal into an intracellular biological function. Here, the conformational dynamics of the neuropeptide Y receptor type 2 (Y2R) during activation was investigated. The apo, full agonist-, and arrestin-bound states of Y2R were prepared by cell-free expression, functional refolding, and reconstitution into lipid membranes. To study conformational transitions between these states, all six tryptophans of Y2R were(13)C-labeled. NMR-signal assignment was achieved by dynamic-nuclear-polarization enhancement and the individual functional states of the receptor were characterized by monitoring(13)C NMR chemical shifts. Activation of Y2R is mediated by molecular switches involving the toggle switch residue Trp281(6.48)of the highly conserved SWLP motif and Trp327(7.55)adjacent to the NPxxY motif. Furthermore, a conformationally preserved "cysteine lock"-Trp116(23.50)was identified

First simultaneous optical/near-infrared imaging of an X-ray selected, high-redshift cluster of galaxies with GROND: the galaxy population of XMMU J0338.7+0030 at z=1.1

The XMM-Newton Distant Cluster Project is a serendipitous survey for clusters of galaxies at redshifts z>=0.8 based on deep archival XMM-Newton observations. ... Low-significance candidate high-z clusters are followed up with the seven-channel imager GROND (Gamma-Ray Burst Optical and Near-Infrared Detector) that is mounted at a 2m-class telescope. ... The test case is XMMU J0338.7+0030, suggested to be at z~1.45+/-0.15 from the analysis of the z-H vs H colour-magnitude diagram obtained from the follow-up imaging. Later VLT-FORS2 spectroscopy enabled us to identify four members, which set this cluster at z=1.097+/-0.002. To reach a better knowledge of its galaxy population, we observed XMMU J0338.7+0030 with GROND for about 6 hr. The publicly available photo-z code le Phare was used. The Ks-band number counts of the non-stellar sources out of the 832 detected down to z'~26 AB-mag in the 3.9x4.3 square arcmin region of XMMU J0338.7+0030 imaged at all GROND bands clearly exceed those computed in deep fields/survey areas at ~20.5 - 22.5 AB-mag. The photo-z's of the three imaged spectroscopic members yield z=1.12+/-0.09. The spatial distribution and the properties of the GROND sources with a photo-z in the range 1.01 - 1.23 confirm the correspondence of the X-ray source with a galaxy over-density at a significance of at least 4.3 sigma. Candidate members that are spectro-photometrically classified as elliptical galaxies define a red locus in the i'-z' vs z' colour-magnitude diagram that is consistent with the red sequence of the cluster RDCS J0910+5422 at z=1.106. XMMU J0338.7+0030 hosts also a population of bluer late-type spirals and irregulars. The starbursts among the photometric members populate both loci, consistently with previous results. The analysis of the available data set indicates that XMMU J0338.7+0030 is a low-mass cluster (M_200 ~ 1E14 M_sun) at z=1.1. (Abridged)Comment: accepted for publication in Astronomy & Astrophysics Main Journal, 27 pages, 24 figures, 1 tabl

The Resonance Frequency Shift, Pattern Formation, and Dynamical Network Reorganization via Sub-Threshold Input

We describe a novel mechanism that mediates the rapid and selective pattern formation of neuronal network activity in response to changing correlations of sub-threshold level input. The mechanism is based on the classical resonance and experimentally observed phenomena that the resonance frequency of a neuron shifts as a function of membrane depolarization. As the neurons receive varying sub-threshold input, their natural frequency is shifted in and out of its resonance range. In response, the neuron fires a sequence of action potentials, corresponding to the specific values of signal currents, in a highly organized manner. We show that this mechanism provides for the selective activation and phase locking of the cells in the network, underlying input-correlated spatio-temporal pattern formation, and could be the basis for reliable spike-timing dependent plasticity. We compare the selectivity and efficiency of this pattern formation to a supra-threshold network activation and a non-resonating network/neuron model to demonstrate that the resonance mechanism is the most effective. Finally we show that this process might be the basis of the phase precession phenomenon observed during firing of hippocampal place cells, and that it may underlie the active switching of neuronal networks to locking at various frequencies

A review of elliptical and disc galaxy structure, and modern scaling laws

A century ago, in 1911 and 1913, Plummer and then Reynolds introduced their models to describe the radial distribution of stars in `nebulae'. This article reviews the progress since then, providing both an historical perspective and a contemporary review of the stellar structure of bulges, discs and elliptical galaxies. The quantification of galaxy nuclei, such as central mass deficits and excess nuclear light, plus the structure of dark matter halos and cD galaxy envelopes, are discussed. Issues pertaining to spiral galaxies including dust, bulge-to-disc ratios, bulgeless galaxies, bars and the identification of pseudobulges are also reviewed. An array of modern scaling relations involving sizes, luminosities, surface brightnesses and stellar concentrations are presented, many of which are shown to be curved. These 'redshift zero' relations not only quantify the behavior and nature of galaxies in the Universe today, but are the modern benchmark for evolutionary studies of galaxies, whether based on observations, N-body-simulations or semi-analytical modelling. For example, it is shown that some of the recently discovered compact elliptical galaxies at 1.5 < z < 2.5 may be the bulges of modern disc galaxies.Comment: Condensed version (due to Contract) of an invited review article to appear in "Planets, Stars and Stellar Systems"(www.springer.com/astronomy/book/978-90-481-8818-5). 500+ references incl. many somewhat forgotten, pioneer papers. Original submission to Springer: 07-June-201

Measurements of Higgs boson production and couplings in diboson final states with the ATLAS detector at the LHC

Measurements are presented of production properties and couplings of the recently discovered Higgs boson using the decays into boson pairs, H →γ γ, H → Z Z∗ →4l and H →W W∗ →lνlν. The results are based on the complete pp collision data sample recorded by the ATLAS experiment at the CERN Large Hadron Collider at centre-of-mass energies of √s = 7 TeV and √s = 8 TeV, corresponding to an integrated luminosity of about 25 fb−1. Evidence for Higgs boson production through vector-boson fusion is reported. Results of combined fits probing Higgs boson couplings to fermions and bosons, as well as anomalous contributions to loop-induced production and decay modes, are presented. All measurements are consistent with expectations for the Standard Model Higgs boson

Standalone vertex finding in the ATLAS muon spectrometer

A dedicated reconstruction algorithm to find decay vertices in the ATLAS muon spectrometer is presented. The algorithm searches the region just upstream of or inside the muon spectrometer volume for multi-particle vertices that originate from the decay of particles with long decay paths. The performance of the algorithm is evaluated using both a sample of simulated Higgs boson events, in which the Higgs boson decays to long-lived neutral particles that in turn decay to bbar b final states, and pp collision data at √s = 7 TeV collected with the ATLAS detector at the LHC during 2011

Single hadron response measurement and calorimeter jet energy scale uncertainty with the ATLAS detector at the LHC

The uncertainty on the calorimeter energy response to jets of particles is derived for the ATLAS experiment at the Large Hadron Collider (LHC). First, the calorimeter response to single isolated charged hadrons is measured and compared to the Monte Carlo simulation using proton-proton collisions at centre-of-mass energies of sqrt(s) = 900 GeV and 7 TeV collected during 2009 and 2010. Then, using the decay of K_s and Lambda particles, the calorimeter response to specific types of particles (positively and negatively charged pions, protons, and anti-protons) is measured and compared to the Monte Carlo predictions. Finally, the jet energy scale uncertainty is determined by propagating the response uncertainty for single charged and neutral particles to jets. The response uncertainty is 2-5% for central isolated hadrons and 1-3% for the final calorimeter jet energy scale.Comment: 24 pages plus author list (36 pages total), 23 figures, 1 table, submitted to European Physical Journal

Measurement of the top quark pair cross section with ATLAS in pp collisions at √s=7 TeV using final states with an electron or a muon and a hadronically decaying τ lepton

A measurement of the cross section of top quark pair production in proton-proton collisions recorded with the ATLAS detector at the Large Hadron Collider at a centre-of-mass energy of 7 TeV is reported. The data sample used corresponds to an integrated luminosity of 2.05 fb -1. Events with an isolated electron or muon and a τ lepton decaying hadronically are used. In addition, a large missing transverse momentum and two or more energetic jets are required. At least one of the jets must be identified as originating from a b quark. The measured cross section, σtt-=186±13(stat.)±20(syst.)±7(lumi.) pb, is in good agreement with the Standard Model prediction