Beta-band intermuscular coherence:A novel biomarker of upper motor neuron dysfunction in motor neuron disease

In motor neuron disease, the focus of therapy is to prevent or slow neuronal degeneration with neuroprotective pharmacological agents; early diagnosis and treatment are thus essential. Incorporation of needle electromyographic evidence of lower motor neuron degeneration into diagnostic criteria has undoubtedly advanced diagnosis, but even earlier diagnosis might be possible by including tests of subclinical upper motor neuron disease. We hypothesized that beta-band (15-30Hz) intermuscular coherence could be used as an electrophysiological marker of upper motor neuron integrity in such patients. We measured intermuscular coherence in eight patients who conformed to established diagnostic criteria for primary lateral sclerosis and six patients with progressive muscular atrophy, together with 16 age-matched controls. In the primary lateral sclerosis variant of motor neuron disease, there is selective destruction of motor cortical layer V pyramidal neurons and degeneration of the corticospinal tract, without involvement of anterior horn cells. In progressive muscular atrophy, there is selective degeneration of anterior horn cells but a normal corticospinal tract. All patients with primary lateral sclerosis had abnormal motor-evoked potentials as assessed using transcranial magnetic stimulation, whereas these were similar to controls in progressive muscular atrophy. Upper and lower limb intermuscular coherence was measured during a precision grip and an ankle dorsiflexion task, respectively. Significant beta-band coherence was observed in all control subjects and all patients with progressive muscular atrophy tested, but not in the patients with primary lateral sclerosis. We conclude that intermuscular coherence in the 15-30Hz range is dependent on an intact corticospinal tract but persists in the face of selective anterior horn cell destruction. Based on the distributions of coherence values measured from patients with primary lateral sclerosis and control subjects, we estimated the likelihood that a given measurement reflects corticospinal tract degeneration. Therefore, intermuscular coherence has potential as a quantitative test of subclinical upper motor neuron involvement in motor neuron disease

The SPL (II) at CERN, a Superconducting 3.5 GeV H- Linac

A revision of the physics needs and recent progress in the technology of superconducting (SC) RF cavities have triggered major changes in the design of a SC H-linac at CERN. With up to 5MW beam power, the SPL can be the proton driver for a next generation ISOL-type radioactive beam facility (âEURISOLâ) and/or supply protons to a neutrino () facility (conventional superbeam + beta-beam or -factory). Furthermore the SPL can replace Linac2 and the PS booster (PSB), improving significantly the beam performance in terms of brightness, intensity, and reliability for the benefit of all proton users at CERN, including LHC and its luminosity upgrade. Compared with the first conceptual design, the beam energy is almost doubled (3.5GeV instead of 2.2 GeV) while the length is reduced by 40%. At a repetition rate of 50 Hz, the linac reuses decommissioned 352.2MHz RF equipment from LEP in the low-energy part. Beyond 90MeV the RF frequency is doubled, and from 180MeV onwards high-gradient SC bulkniobium cavities accelerate the beam to its final energy of 3.5GeV. This paper presents the overall design approach, together with the technical progress since the first conceptual design in 2000

Topical Review on "Beta-beams"

Neutrino physics is traversing an exciting period, after the important discovery that neutrinos are massive particles, that has implications from high-energy physics to cosmology. A new method for the production of intense and pure neutrino beams has been proposed recently: the ``beta-beam''. It exploits boosted radioactive ions decaying through beta-decay. This novel concept has been the starting point for a new possible future facility. Its main goal is to address the crucial issue of the existence of CP violation in the lepton sector. Here we review the status and the recent developments with beta-beams. We discuss the original, the medium and high-energy scenarios as well as mono-chromatic neutrino beams produced through ion electron-capture. The issue of the degeneracies is mentioned. An overview of low energy beta-beams is also presented. These beams can be used to perform experiments of interest for nuclear structure, for the study of fundamental interactions and for nuclear astrophysics.Comment: Topical Review for Journal of Physics G: Nuclear and Particle Physics, published version, minor corrections, references adde

Linac4 Technical Design Report

Linac4 is an H- linear accelerator, intended to replace Linac2 as injector to the PS Booster (PSB). By delivering to the PSB a beam at 160 MeV energy, Linac4 will provide the conditions to double the brightness and intensity of the beam from the PSB, thus removing the first bottleneck towards higher brightness for the LHC and simplifying operation. Moreover, this new linac constitutes an essential component of any of the envisaged LHC upgrade scenarios and could open the way to future extensions of the CERN accelerator complex towards higher performance. This Technical Design Report presents a detailed technical overview of the Linac4 design as it stands at end 2006

Divergence of gut permeability and mucosal immune gene expression in two gluten-associated conditions: celiac disease and gluten sensitivity

<p>Abstract</p> <p>Background</p> <p>Celiac disease (CD) is an autoimmune enteropathy triggered by the ingestion of gluten. Gluten-sensitive individuals (GS) cannot tolerate gluten and may develop gastrointestinal symptoms similar to those in CD, but the overall clinical picture is generally less severe and is not accompanied by the concurrence of tissue transglutaminase autoantibodies or autoimmune comorbidities. By studying and comparing mucosal expression of genes associated with intestinal barrier function, as well as innate and adaptive immunity in CD compared with GS, we sought to better understand the similarities and differences between these two gluten-associated disorders.</p> <p>Methods</p> <p>CD, GS and healthy, gluten-tolerant individuals were enrolled in this study. Intestinal permeability was evaluated using a lactulose and mannitol probe, and mucosal biopsy specimens were collected to study the expression of genes involved in barrier function and immunity.</p> <p>Results</p> <p>Unlike CD, GS is not associated with increased intestinal permeability. In fact, this was significantly reduced in GS compared with controls (<it>P </it>= 0.0308), paralleled by significantly increased expression of claudin (CLDN) 4 (<it>P </it>= 0.0286). Relative to controls, adaptive immunity markers interleukin (IL)-6 (<it>P </it>= 0.0124) and IL-21 (<it>P </it>= 0.0572) were expressed at higher levels in CD but not in GS, while expression of the innate immunity marker Toll-like receptor (TLR) 2 was increased in GS but not in CD (<it>P </it>= 0.0295). Finally, expression of the T-regulatory cell marker FOXP3 was significantly reduced in GS relative to controls (<it>P </it>= 0.0325) and CD patients (<it>P </it>= 0.0293).</p> <p>Conclusions</p> <p>This study shows that the two gluten-associated disorders, CD and GS, are different clinical entities, and it contributes to the characterization of GS as a condition associated with prevalent gluten-induced activation of innate, rather than adaptive, immune responses in the absence of detectable changes in mucosal barrier function.</p

RPC-based Muon Identification System for the neutrino detector of the SHiP experiment

The SHiP experiment has been proposed at CERN to shed light on phenomena still unexplained in the framework of the Standard Model, such as the nature of dark matter, the baryonic asymmetry of the Universe and the neutrino oscillations, searching for hints of New Physics. A section of the detector will be dedicated to the study of neutrino physics with special emphasis on tau neutrino properties, still very poorly measured. A system to identify the muons produced in neutrino interactions, based on RPC technology, has been proposed and it is presented in detail in this paper

Engineering reconnaissance following the August 24, 2016 M6.0 Central Italy earthquake

An earthquake with a moment magnitude reported as 6.0 from INGV (Istituto Nazionale di Geofisica e Vulcanologia); occurred at 03:36 AM (local time) on 24 August 2016 in the central part of Italy. The epicenter was located at the borders of the Lazio, Abruzzi, Marche and Umbria regions, about 2.5 km north-east of the village of Accumoli and about 100 km from Rome. The hypocentral depth was about 8 km (INGV). We summarize preliminary findings of the Italy-US GEER (Geotechnical Extreme Events Reconnaissance) team, on damage distribution, causative faults, earthquake-induced landslides and rockfalls, building and bridge performance, and ground motion characterization. Our reconnaissance team used multidisciplinary approaches, combining expertise in geology, seismology, geomatics, geotechnical engineering, and structural engineering. Our approach was to combine traditional reconnaissance activities of on-ground recording and mapping of field conditions, with advanced imaging and damage detection routines enabled by state-of-the-art geomatics technology. We anticipate that results from this study, will be useful for future post-earthquake reconnaissance efforts, and improved emergency respons

Dietary and lifestyle determinants of acrylamide and glycidamide hemoglobin adducts in non-smoking postmenopausal women from the EPIC cohort

Purpose Acrylamide was classified as 'probably carcinogenic' to humans in 1994 by the International Agency for Research on Cancer. In 2002, public health concern increased when acrylamide was identified in starchy, plant-based foods, processed at high temperatures. The purpose of this study was to identify which food groups and lifestyle variables were determinants of hemoglobin adduct concentrations of acrylamide (HbAA) and glycidamide (HbGA) in 801 non-smoking postmenopausal women from eight countries in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Methods Biomarkers of internal exposure were measured in red blood cells (collected at baseline) by high-performance liquid chromatography/tandem mass spectrometry (HPLC/MS/MS) . In this cross-sectional analysis, four dependent variables were evaluated: HbAA, HbGA, sum of total adducts (HbAA + HbGA), and their ratio (HbGA/HbAA). Simple and multiple regression analyses were used to identify determinants of the four outcome variables. All dependent variables (except HbGA/HbAA) and all independent variables were log-transformed (log2) to improve normality. Median (25th-75th percentile) HbAA and HbGA adduct levels were 41.3 (32.8-53.1) pmol/g Hb and 34.2 (25.4-46.9) pmol/g Hb, respectively. Results The main food group determinants of HbAA, HbGA, and HbAA + HbGA were biscuits, crackers, and dry cakes. Alcohol intake and body mass index were identified as the principal determinants of HbGA/HbAA. The total percent variation in HbAA, HbGA, HbAA + HbGA, and HbGA/HbAA explained in this study was 30, 26, 29, and 13 %, respectively. Conclusions Dietary and lifestyle factors explain a moderate proportion of acrylamide adduct variation in non-smoking postmenopausal women from the EPIC cohort