Lower extremity muscle pathology in myotonic dystrophy type 1 assessed by quantitative MRI

Objective: To determine the value of quantitative MRI in providing imaging biomarkers for disease in 20 different upper and lower leg muscles of patients with myotonic dystrophy type 1 (DM1). Methods: We acquired images covering these muscles in 33 genetically and clinically well-characterized patients with DM1 and 10 unaffected controls. MRIs were recorded with a Dixon method to determine muscle fat fraction, muscle volume, and contractile muscle volume, and a multi-echo spin-echo sequence was used to determine T2 water relaxation time (T2water), reflecting putative edema. Results: Muscles in patients with DM1 had higher fat fractions than muscles of controls (15.6 ± 11.1% vs 3.7 ± 1.5%). In addition, patients had smaller muscle volumes (902 ± 232 vs 1,097 ± 251 cm3), smaller contractile muscle volumes (779 ± 247 vs 1,054 ± 246 cm3), and increased T2water (33.4 ± 1.0 vs 31.9 ± 0.6 milliseconds), indicating atrophy and edema, respectively. Lower leg muscles were affected most frequently, especially the gastrocnemius medialis and soleus. Distribution of fat content per muscle indicated gradual fat infiltration in DM1. Between-patient variation in fat fraction was explained by age (≈45%), and another ≈14% was explained by estimated progenitor CTG repeat length (r2 = 0.485) and somatic instability (r2 = 0.590). Fat fraction correlated with the 6-minute walk test (r = −0.553) and muscular impairment rating scale (r = 0.537) and revealed subclinical muscle involvement. Conclusion: This cross-sectional quantitative MRI study of 20 different lower extremity muscles in patients with DM1 revealed abnormal values for muscle fat fraction, volume, and T2water, which therefore may serve as objective biomarkers to assess disease state of skeletal muscles in these patients

Search for black holes and other new phenomena in high-multiplicity final states in proton-proton collisions at root s=13 TeV

Peer reviewe

Search for heavy resonances decaying into a vector boson and a Higgs boson in final states with charged leptons, neutrinos, and b quarks

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Search for high-mass diphoton resonances in proton-proton collisions at 13 TeV and combination with 8 TeV search

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Search for leptophobic Z ' bosons decaying into four-lepton final states in proton-proton collisions at root s=8 TeV

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The role of stakeholder involvement in the evolving EU HTA process:Insights generated through the European Access Academy’s multi-stakeholder pre-convention questionnaire

Involvement of all relevant stakeholders will be of utmost importance for the success of the developing EU HTA harmonization process. A multi-step procedure was applied to develop a survey across stakeholders/collaborators within the EU HTA framework to assess their current level of involvement, determine their suggested future role, identify challenges to contribution, and highlight efficient ways to fulfilling their role. The ‘key’ stakeholder groups identified and covered by this research included: patients‘, clinicians‘, regulatory, and Health Technology Developer representatives. The survey was circulated to a wide expert audience including all relevant stakeholder groups in order to determine self-perception by the ‘key’ stakeholders regarding involvement in the HTA process (self-rating), and in a second, slightly modified version of the questionnaire, to determine the perception of ‘key’ stakeholder involvement by HTA bodies, payers, and policymakers (external rating). Predefined analyses were conducted on the submitted responses. Fifty-four responses were received (patients 9; clinicians: 8; regulators: 4; HTDs 14; HTA bodies: 7; Payers: 5; policymakers 3; others 4). The mean self-perceived involvement score was consistently lower for each of the ‘key’ stakeholder groups than the respective external ratings. Based on the qualitative insights generated in the survey, a RACI Chart (Responsible/Accountable/Consulted/Informed) was developed for each of the stakeholder groups to determine their roles and involvement in the current EU HTA process. Our findings suggest extensive effort and a distinct research agenda are required to ensure adequate involvement of the key stakeholder groups in the evolving EU HTA process.</p

Performance of reconstruction and identification of τ leptons decaying to hadrons and vτ in pp collisions at √s=13 TeV

The algorithm developed by the CMS Collaboration to reconstruct and identify τ leptons produced in proton-proton collisions at √s=7 and 8 TeV, via their decays to hadrons and a neutrino, has been significantly improved. The changes include a revised reconstruction of π⁰ candidates, and improvements in multivariate discriminants to separate τ leptons from jets and electrons. The algorithm is extended to reconstruct τ leptons in highly Lorentz-boosted pair production, and in the high-level trigger. The performance of the algorithm is studied using proton-proton collisions recorded during 2016 at √s=13 TeV, corresponding to an integrated luminosity of 35.9 fb¯¹. The performance is evaluated in terms of the efficiency for a genuine τ lepton to pass the identification criteria and of the probabilities for jets, electrons, and muons to be misidentified as τ leptons. The results are found to be very close to those expected from Monte Carlo simulation

Search for top squark pair production in compressed-mass-spectrum scenarios in proton-proton collisions at √s=8 TeV using the αT_{T} variable

An inclusive search is performed for supersymmetry in final states containing jets and an apparent imbalance in transverse momentum, (p) over right arrow (miss)(T),due to the production of unobserved weakly interacting particles in pp collisions at a centre-of-mass energy of 8 TeV. The data, recorded with the CMS detector at the CERN LHC, correspond to an integrated luminosity of 18.5fb(-1). The dimensionless kinematic variable alpha(T) is used to discriminate between events with genuine (p) over right arrow (miss)(T)associated with unobserved particles and spurious values of (p) over right arrow (miss)(T) Tarising from jet energy mismeasurements. No excess of event yields above the expected standard model backgrounds is observed. The results are interpreted in terms of constraints on the parameter space of several simplified models of supersymmetry that assume the pair production of top squarks. The search provides sensitivity to a broad range of top squark ((t) over tilde) decay modes, including the two-body decay (t)over tilde> -> c (chi) over tilde (0)(1),where c is a charm quark (chi) over tilde (0)(1) and is the lightest neutralino, as well as the four-body decay (t)over tilde> -> bf (f) over bar' (chi) over bar (0)(1),where b is a bottom quark and f and (f) over bar' are fermions produced in the decay of an intermediate off-shell W boson. These modes dominate in scenarios in which the top squark and lightest neutralino are nearly degenerate in mass. For these modes, top squarks with masses as large as 260 and 225 GeV are excluded, respectively, for the two-and four-body decays. (C) 2017 The Author. Published by Elsevier B.V