The UK myotonic dystrophy patient registry: facilitating and accelerating clinical research

Myotonic dystrophy type 1 (DM1) is the most frequent muscular dystrophy worldwide with complex, multi-systemic, and progressively worsening symptoms. There is currently no treatment for this inherited disorder and research can be challenging due to the rarity and variability of the disease. The UK Myotonic Dystrophy Patient Registry is a patient self-enrolling online database collecting clinical and genetic information. For this cross-sectional “snapshot” analysis, 556 patients with a confirmed diagnosis of DM1 registered between May 2012 and July 2016 were included. An almost even distribution was seen between genders and a broad range of ages was present from 8 months to 78 years, with the largest proportion between 30 and 59 years. The two most frequent symptoms were fatigue and myotonia, reported by 79 and 78% of patients, respectively. The severity of myotonia correlated with the severity of fatigue as well as mobility impairment, and dysphagia occurred mostly in patients also reporting myotonia. Men reported significantly more frequent severe myotonia, whereas severe fatigue was more frequently reported by women. Cardiac abnormalities were diagnosed in 48% of patients and more than one-third of them needed a cardiac implant. Fifteen percent of patients used a non-invasive ventilation and cataracts were removed in 26% of patients, 65% of which before the age of 50 years. The registry’s primary aim was to facilitate and accelerate clinical research. However, these data also allow us to formulate questions for hypothesis-driven research that may lead to improvements in care and treatment

PoGOLite - A High Sensitivity Balloon-Borne Soft Gamma-ray Polarimeter

We describe a new balloon-borne instrument (PoGOLite) capable of detecting 10% polarisation from 200mCrab point-like sources between 25 and 80keV in one 6 hour flight. Polarisation measurements in the soft gamma-ray band are expected to provide a powerful probe into high-energy emission mechanisms as well as the distribution of magnetic fields, radiation fields and interstellar matter. At present, only exploratory polarisation measurements have been carried out in the soft gamma-ray band. Reduction of the large background produced by cosmic-ray particles has been the biggest challenge. PoGOLite uses Compton scattering and photo-absorption in an array of 217 well-type phoswich detector cells made of plastic and BGO scintillators surrounded by a BGO anticoincidence shield and a thick polyethylene neutron shield. The narrow FOV (1.25msr) obtained with well-type phoswich detector technology and the use of thick background shields enhance the detected S/N ratio. Event selections based on recorded phototube waveforms and Compton kinematics reduce the background to that expected for a 40-100mCrab source between 25 and 50keV. A 6 hour observation on the Crab will differentiate between the Polar Cap/Slot Gap, Outer Gap, and Caustic models with greater than 5 sigma; and also cleanly identify the Compton reflection component in the Cygnus X-1 hard state. The first flight is planned for 2010 and long-duration flights from Sweden to Northern Canada are foreseen thereafter.Comment: 11 pages, 11 figures, 2 table

A Solve-RD ClinVar-based reanalysis of 1522 index cases from ERN-ITHACA reveals common pitfalls and misinterpretations in exome sequencing

Purpose Within the Solve-RD project (https://solve-rd.eu/), the European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies aimed to investigate whether a reanalysis of exomes from unsolved cases based on ClinVar annotations could establish additional diagnoses. We present the results of the “ClinVar low-hanging fruit” reanalysis, reasons for the failure of previous analyses, and lessons learned. Methods Data from the first 3576 exomes (1522 probands and 2054 relatives) collected from European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies was reanalyzed by the Solve-RD consortium by evaluating for the presence of single-nucleotide variant, and small insertions and deletions already reported as (likely) pathogenic in ClinVar. Variants were filtered according to frequency, genotype, and mode of inheritance and reinterpreted. Results We identified causal variants in 59 cases (3.9%), 50 of them also raised by other approaches and 9 leading to new diagnoses, highlighting interpretation challenges: variants in genes not known to be involved in human disease at the time of the first analysis, misleading genotypes, or variants undetected by local pipelines (variants in off-target regions, low quality filters, low allelic balance, or high frequency). Conclusion The “ClinVar low-hanging fruit” analysis represents an effective, fast, and easy approach to recover causal variants from exome sequencing data, herewith contributing to the reduction of the diagnostic deadlock

PoGOLite : The Polarised Gamma-ray Observer

PoGOLite is a balloon-borne experiment which will study polarised soft gamma-ray emission from astrophysical targets in the 25 keV – 80 keV energy range by applying well-type phoswich detector technology. Polarised gamma-rays are expected from a wide variety of sources including rotation-powered pulsars, accreting black holes and neutron stars, and jet-dominated active galaxies. Polarisation measurements provide a powerful probe of the gamma-ray emission mechanism and the distribution of magnetic and radiation fields around the source. The polarisation is determined using Compton scattering and photoelectric absorption in an array of 217 plastic scintillators. The sensitive detector is surrounded by a segmented Bismuth Germanium Oxide (BGO) anticoincidence shield. The function of this shield is to reduce backgrounds from charged cosmic rays, primary and atmospheric gamma-rays, and atmospheric and instrumental neutrons. The anticoincidence shield consists of 427 BGO crystals with three different geometries. The characteristics of the BGO crystals of the bottom anticoincidence shield have been studied with particular focus on the light yield. The PoGOLite polarimeter has a field of view of 2.4° x 2.4° and must be kept aligned to objects of interest on the sky. A star tracker forms part of the attitude control system. The star tracker system comprises a CCD camera, lens, and a baffle system. Preliminary studies have been made concerning optimization of the focus, flat field correction, map of hot pixel and CCD response. An estimate of the star magnitude limit is also derived and found to be compatible with the environment around the Crab, which is the first observational target. These studies pave the way toward an autonomous star tracking device which together with the other attitude control devices will reconstruct the pointing solution.QC 2010111

Performance Studies and Star Tracking for PoGOLite

PoGOLite is a balloon-borne experiment, which will study polarized soft γ-ray emissionfrom astrophysical targets in the 25-80 keV energy range by applying well-typephoswich detector technology. Polarized γ-rays are expected from a wide variety of sources including rotation-powered pulsars, accreting black holes and neutron stars,and jet-dominated active galaxies. Polarization measurements provide a powerfulprobe of the γ-ray emission mechanism and the distribution of magnetic and radiation fields around the source. The polarization is determined using Compton scattering and photoelectric absorption in an array of 217 plastic scintillators. The sensitive detector is surrounded by a segmented Bismuth Germanium Oxide (BGO) anticoincidence shield. The function of this shield is to reduce backgrounds from charged cosmic rays, primary and atmospheric γ-rays, and atmospheric and instrumenta lneutrons. The anticoincidence shield consists of 427 BGO crystals with three different geometries. The characteristics of the BGO crystals of the bottom anticoincidence shield have been studied with particular focus on the light yield.The maiden flight of PoGOLite will be with a reduced detector volume “pathfinder” instrument. The flight, lasting about 24 hours, is foreseen from Esrange, Sweden in August 2010. The performance of the pathfinder has been studied using computer simulations. The effect of atmospheric attenuation, both on the signal of theastronomical target and on the background, are studied. These allow an observationstrategy to be developed for the forthcoming flight. A polarization analysis method is described and applied to an observation example. The method sets anupper limit on the accuracy with which the polarimeter will be able to detect polarization the angle and degree. The PoGOLite polarimeter has a relatively small field of view (2.4◦×2.4◦) which must be kept aligned to objects of interest on the sky. A star tracker forms part of the attitude control system. The star trackersystem comprises a CCD camera, a lens, and a baffle system. Preliminary studiesof the star identification performance are presented and are found to be compatible with the environment around the Crab, which is the main observational target for the first flight.QC2010062

PoGOLite : The Polarised Gamma-ray Observer

PoGOLite is a balloon-borne experiment which will study polarised soft gamma-ray emission from astrophysical targets in the 25 keV – 80 keV energy range by applying well-type phoswich detector technology. Polarised gamma-rays are expected from a wide variety of sources including rotation-powered pulsars, accreting black holes and neutron stars, and jet-dominated active galaxies. Polarisation measurements provide a powerful probe of the gamma-ray emission mechanism and the distribution of magnetic and radiation fields around the source. The polarisation is determined using Compton scattering and photoelectric absorption in an array of 217 plastic scintillators. The sensitive detector is surrounded by a segmented Bismuth Germanium Oxide (BGO) anticoincidence shield. The function of this shield is to reduce backgrounds from charged cosmic rays, primary and atmospheric gamma-rays, and atmospheric and instrumental neutrons. The anticoincidence shield consists of 427 BGO crystals with three different geometries. The characteristics of the BGO crystals of the bottom anticoincidence shield have been studied with particular focus on the light yield. The PoGOLite polarimeter has a field of view of 2.4° x 2.4° and must be kept aligned to objects of interest on the sky. A star tracker forms part of the attitude control system. The star tracker system comprises a CCD camera, lens, and a baffle system. Preliminary studies have been made concerning optimization of the focus, flat field correction, map of hot pixel and CCD response. An estimate of the star magnitude limit is also derived and found to be compatible with the environment around the Crab, which is the first observational target. These studies pave the way toward an autonomous star tracking device which together with the other attitude control devices will reconstruct the pointing solution.QC 2010111

The 2.5 MeV neutron flux monitor for MAST

A proof-of-principle collimated Neutron flux Camera (NC) monitor for the measurement of the 2.45 MeV neutron emission from the deuterium-deuterium fusion reactions has been developed, installed and put into use at the Mega Ampere Spherical Tokamak (MAST). The NC measures the spatial and time resolved volume integrated neutron emissivity in deuterium fusion plasmas in the presence of auxiliary plasma heating along two equatorial and two diagonal lines of sight whose tangency radius can be varied between plasma discharges. This paper describes the NC design principles, their technical realization and its performances illustrated with experimental observations of different plasma scenarios. Neutron. count rates in the range 0.1-1.5 MHz are routinely observed allowing time resolutions as high as 1 ms with a statistical uncertainty less than 10% and an energy threshold of 0.5 MeV. Examples of the effect of plasma instabilities on the neutron emission are presented. The good results obtained will be used for the design of the neutron flux camera monitor for MAST Upgrade.

The OLIMPO experiment

OLIMPO is a high resolution balloon-borne telescope. It will measure the Sunyaev-Zeldovich effect in clusters of galaxies during a long-duration flight. OLIMPO will carry out a survey of 40 clusters in four frequency bands centered at 140, 220, 410 and 540 GHz. We describe here the OLIMPO instrument and its scientific goals. (c) 2006 Elsevier B.V. All rights reserved

OLIMPO: a multi-frequency survey of galaxy clusters and of the cosmic millimetric background

International School of Physics "Enrico Fermi", Course CLI

OLIMPO: a multi-frequency survey of galaxy clusters and of the cosmic millimetric background

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