Autoimmunity at the neuromuscular synapse: pathophysiology and disease course

This thesis addresses several pathophysiological and clinical aspects of both the Lambert-Eaton myasthenic syndrome (LEMS, introduced in chapter 1) and myasthenia gravis (MG).In chapter 2, the search for new LEMS associated small cell lung cancer (SCLC) markers is described, leading to the discovery of ERC1 as a new antigen associated with LEMS.In chapter 3, a literature review of screening methods for SCLC in LEMS is presented, aswell as the role of associated SOX1 antibodies in SCLC-LEMS patients.In chapter 4 long-term follow-up, functional impairment and quality of life in LEMSpatients are described. We also report a normal survival in LEMS patients without associated tumour as well as an improved tumour survival in SCLC-LEMS patients.In chapter 5, we report that lowering the cut-off value for increment from 100% to 60% increases sensitivity for diagnosis of LEMS, without a negative effect on the specificity.Chapter 6 reports that a lower initial compound muscle action potential amplitude is a marker of more severe disease in AChR MG.In chapter 7, we show a small symptomatic effect of ephedrine as a symptomatic treatment in MG patients, in a placebo-controlled, double-blind, randomised, multiple crossover series of n-of-1 trials.LUMC / Geneeskund

Lowering the cutoff value for increment increases the sensitivity for the diagnosis of Lambert-Eaton myasthenic syndrome

Background: Increment of compound muscle action potential amplitude is a diagnostic hallmark of Lambert-Eaton myasthenic syndrome (LEMS). Making a diagnosis can be challenging, therefore, a proper cutoff for abnormal increment is highly relevant for improved recognition

Accuracy of patient-reported data for an online patient registry of autoimmune myasthenia gravis and Lambert-Eaton myasthenic syndrome

Disorders of the neuromuscular junction (NMJ) comprise a spectrum of rare diseases causing muscle fatigability and weakness, leading to life-long effects on quality of life. We established the Dutch-Belgian registry for NMJ disorders, based on a unique combination of patient -and physician-reported information. Information on natural course, disease burden, prevalence of complications and comorbidity is collected through patient-reported standardized questionnaires and verified using medical documentation. Currently, the registry contains information of 565 Myasthenia Gravis (MG) patients and 38 Lambert-Eaton myasthenic syndrome (LEMS) patients, constituting approximately 25% (MG) and 80% (LEMS) of patients in the Netherlands. This is a very large registry, with the highest participation rate per capita. In addition to confirming many disease characteristics previously described in the literature, this registry provides several novel insights. The reported rate of potentially corticosteroid-related comorbidity, including hypertension, heart disease, osteoporosis and type 2 diabetes was high, emphasizing the need to commence corticosteroid-sparing immune suppressive treatment as soon as possible. The reported rate of other auto-immune diseases is far higher than previously expected: 27% of MG and 38% of LEMS patients, and a surprisingly high number of MG patients (47%) is unaware of their antibody status. In conclusion, this registry provides a valuable collection of information regarding MG and LEMS disease course. Continuous collection of annual follow-up data will provide further longitudinal insights in disease burden, course and treatment effect. (c) 2021 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY license ( http://creativecommons.org/licenses/by/4.0/ )Neurological Motor Disorder

Development of aerogel Cherenkov detectors at Novosibirsk

Abstract The development of aerogel Cherenkov counters with the light collection using a wavelength shifter is described. 80 counters of this type are working in the KEDR detector. A project of similar counters for the SND detector based on "heavy" aerogel with n = 1.13 has been developed. Aerogel with a refractive index of 1.006–1.13 and dimensions of blocks up to 200 × 200 × 50 mm 3 is produced by the Novosibirsk group for use in Cherenkov counters of different types. The Novosibirsk group is participating in the development of LHCb RICH as well as a beam diagnostics for a photo-injector test facility at DESY–Zeuthen. Recently we started development of RICH based on focusing aerogel (FARICH) for the endcap of the SuperBaBar. For the first time in the world the focusing aerogel with layers of different refractive indices has been produced

Development of aerogel Cherenkov counters at Novosibirsk

Abstract The work on aerogel Cherenkov counters was started in Novosibirsk in 1986. Production of aerogels with refractive indices of 1.006–1.13 and thicknesses of blocks up to 50 mm was developed. The light absorption length at 400 nm is 5–7 m, the scattering length is 4–5 cm. By these parameters, the Novosibirsk aerogel is one of the best in the world. The ASHIPH Cherenkov counters with light collection on wavelength shifters have been developed. The ASHIPH system of the KEDR detector contains 1000 l of aerogel. The π / K separation is 4.5 σ . A project of ASHIPH counters for the SND detector has been developed. Aerogel RICH for LHCb gives a possibility to identify hadrons in the momentum range of 2–10 GeV/c. The Novosibirsk group is developing an aerogel RICH for the endcap for the SuperBaBar project. Calculations performed by a group of physicists from Novosibirsk and DESY-Zeuthen have shown that aerogel radiators enable to achieve time resolution up to 20 fs

Measurement of the mass difference between top quark and antiquark in pp collisions at root s=8 TeV

Peer reviewe

Search for jet extinction in the inclusive jet-pT spectrum from proton-proton collisions at s=8 TeV

Published by the American Physical Society under the terms of the Creative Commons Attribution 3.0 License. Further distribution of this work must maintain attribution to the author(s) and the published articles title, journal citation, and DOI.The first search at the LHC for the extinction of QCD jet production is presented, using data collected with the CMS detector corresponding to an integrated luminosity of 10.7  fb−1 of proton-proton collisions at a center-of-mass energy of 8 TeV. The extinction model studied in this analysis is motivated by the search for signatures of strong gravity at the TeV scale (terascale gravity) and assumes the existence of string couplings in the strong-coupling limit. In this limit, the string model predicts the suppression of all high-transverse-momentum standard model processes, including jet production, beyond a certain energy scale. To test this prediction, the measured transverse-momentum spectrum is compared to the theoretical prediction of the standard model. No significant deficit of events is found at high transverse momentum. A 95% confidence level lower limit of 3.3 TeV is set on the extinction mass scale

Search for the associated production of the Higgs boson with a top-quark pair

A search for the standard model Higgs boson produced in association with a top-quark pair t t ¯ H (tt¯H) is presented, using data samples corresponding to integrated luminosities of up to 5.1 fb −1 and 19.7 fb −1 collected in pp collisions at center-of-mass energies of 7 TeV and 8 TeV respectively. The search is based on the following signatures of the Higgs boson decay: H → hadrons, H → photons, and H → leptons. The results are characterized by an observed t t ¯ H tt¯H signal strength relative to the standard model cross section, μ = σ/σ SM ,under the assumption that the Higgs boson decays as expected in the standard model. The best fit value is μ = 2.8 ± 1.0 for a Higgs boson mass of 125.6 GeV