Constitutional mismatch repair deficiency (CMMRD) presenting with high-grade glioma, multiple developmental venous anomalies and malformations of cortical development-a multidisciplinary/multicentre approach and neuroimaging clues to clinching the diagnosis

Constitutional mismatch repair deficiency syndrome (CMMRD) is a rare cancer-predisposition syndrome associated with a high risk of developing a spectrum of malignancies in childhood and adolescence, including brain tumours. In this report, we present the case of an 8-year-old boy with acute headache, vomiting and an episode of unconsciousness in whom brain imaging revealed a high-grade glioma (HGG). The possibility of an underlying diagnosis of CMMRD was suspected radiologically on the basis of additional neuroimaging findings, specifically the presence of multiple supratentorial and infratentorial developmental venous anomalies (DVAs) and malformations of cortical development (MCD), namely, heterotopic grey matter. The tumour was debulked and confirmed to be a HGG on histopathology. The suspected diagnosis of CMMRD was confirmed on immunohistochemistry and genetic testing which revealed mutations in PMS2 and MSH6. The combination of a HGG, multiple DVAs and MCD in a paediatric or young adult patient should prompt the neuroradiologist to suggest an underlying diagnosis of CMMRD. A diagnosis of CMMRD has an important treatment and surveillance implications not only for the child but also the family in terms of genetic counselling

Conductance and application of organic molecule pairs as nanofuses

We propose that a pair of organic molecules can mimic the behavior of a macroscopic fuse at nanoscale, one component of the pair being the on state and the other the off state. For this task wemake use of density-functional theory to calculate the physical properties of selected molecules, which have also been synthesized by our team. By this means we obtain the transmission spectra and the current of the proposed devices, which allows us to compare the behavior of the on and off states.Of particular interest is the on/off switch ratios, defined as the current ratios of the on and off structures at the corresponding bias voltage. In a first stage, we examine the best linker between the device and the electrode for high on/off switch ratios. Once this is determined, we test the influence of the electron richness of the system to provide a high on/off switch ratio. The entire analysis is also supported by the molecular projected self-consistent Hamiltonian, which provides a good way of understanding the molecular behavior. All the calculations support that interesting on/off switch ratios of two orders of magnitude could be obtained with these prototypical nanofusesWe thank the Regional Government of Andalucía for financial support (Projects No. P06-FQM-01726 and No. P09-FQM-04571), the “Centro de Supercomputación de la Universidad de Granada,” and the “Centro de Computación Científica-UAM” for computation time. The authors are also grateful to the Spanish Secretaría de Estado de Universidades e Investigación, Ministerio de Educación y Ciencia, for financial support within research projects TEC2007-66812 and TEC2010-16211. N.F. thanks the Regional Government of Andalucía for her research contract, and LAC thanks the University of Granada for his research contrac

Hughes Abdominal Repair Trial (HART) – Abdominal wall closure techniques to reduce the incidence of incisional hernias: study protocol for a randomised controlled trial

Background Incisional hernias are common complications of midline closure following abdominal surgery and cause significant morbidity, impaired quality of life and increased health care costs. The ‘Hughes Repair’ combines a standard mass closure with a series of horizontal and two vertical mattress sutures within a single suture. This theoretically distributes the load along the incision length as well as across it. There is evidence to suggest that this technique is as effective as mesh repair for the operative management of incisional hernias; however, no trials have compared the Hughes Repair with standard mass closure for the prevention of incisional hernia formation following a midline incision. Methods/design This is a 1:1 randomised controlled trial comparing two suture techniques for the closure of the midline abdominal wound following surgery for colorectal cancer. Full ethical approval has been gained (Wales REC 3, MREC 12/WA/0374). Eight hundred patients will be randomised from approximately 20 general surgical units within the United Kingdom. Patients undergoing open or laparoscopic (more than a 5-cm midline incision) surgery for colorectal cancer, elective or emergency, are eligible. Patients under the age of 18 years, those having mesh inserted or undergoing musculofascial flap closure of the perineal defect in abdominoperineal wound closure, and those unable to give informed consent will be excluded. Patients will be randomised intraoperatively to either the Hughes Repair or standard mass closure. The primary outcome measure is the incidence of incisional hernias at 1 year as assessed by standardised clinical examination. The secondary outcomes include quality of life patient-reported outcome measures, cost-utility analysis, incidence of complete abdominal wound dehiscence and C-POSSUM scores. The incidence of incisional hernia at 1 year, assessed by computerised tomography, will form a tertiary outcome. Discussion A feasibility phase has been completed. The results of the study will be used to inform current and future practice and potentially reduce the risk of incisional hernia formation following midline incisions

A case series of Diffuse Glioneuronal Tumours with Oligodendroglioma-like features and Nuclear Clusters (DGONC).

In this study, we report three paediatric cases of Diffuse Glioneuronal Tumours with Oligodendroglioma-like features and Nuclear Clusters (DGONC)

Cosmic-Ray Anisotropies in Right Ascension Measured by the Pierre Auger Observatory

We present measurements of the large-scale cosmic-ray (CR) anisotropies in R.A., using data collected by the surface detector array of the Pierre Auger Observatory over more than 14 yr. We determine the equatorial dipole component, through a Fourier analysis in R.A. that includes weights for each event so as to account for the main detector-induced systematic effects. For the energies at which the trigger efficiency of the array is small, the east-west method is employed. Besides using the data from the array with detectors separated by 1500 m, we also include data from the smaller but denser subarray of detectors with 750 m separation, which allows us to extend the analysis down to ∼0.03 EeV. The most significant equatorial dipole amplitude obtained is that in the cumulative bin above 8 EeV, %, which is inconsistent with isotropy at the 6σ level. In the bins below 8 EeV, we obtain 99% CL upper bounds on d ⊥ at the level of 1%-3%. At energies below 1 EeV, even though the amplitudes are not significant, the phases determined in most of the bins are not far from the R.A. of the Galactic center, at GC =-94°, suggesting a predominantly Galactic origin for anisotropies at these energies. The reconstructed dipole phases in the energy bins above 4 EeV point instead to R.A. that are almost opposite to the Galactic center one, indicative of an extragalactic CR origin

Extraction of the Muon Signals Recorded with the Surface Detector of the Pierre Auger Observatory Using Recurrent Neural Networks

We present a method based on the use of Recurrent Neural Networks to extract the muon component from the time traces registered with water-Cherenkov detector (WCD) stations of the Surface Detector of the Pierre Auger Observatory. The design of the WCDs does not allow to separate the contribution of muons to the time traces obtained from the WCDs from those of photons, electrons and positrons for all events. Separating the muon and electromagnetic components is crucial for the determination of the nature of the primary cosmic rays and properties of the hadronic interactions at ultra-high energies. We trained a neural network to extract the muon and the electromagnetic components from the WCD traces using a large set of simulated air showers, with around 450 000 simulated events. For training and evaluating the performance of the neural network, simulated events with energies between 1018.5 eV and 1020 eV and zenith angles below 60 degrees were used. We also study the performance of this method on experimental data of the Pierre Auger Observatory and show that our predicted muon lateral distributions agree with the parameterizations obtained by the AGASA collaboration

Extraction of the Muon Signals Recorded with the Surface Detector of the Pierre Auger Observatory Using Recurrent Neural Networks

The Pierre Auger Observatory, at present the largest cosmic-ray observatory ever built, is instrumented with a ground array of 1600 water-Cherenkov detectors, known as the Surface Detector (SD). The SD samples the secondary particle content (mostly photons, electrons, positrons and muons) of extensive air showers initiated by cosmic rays with energies ranging from $10^{17}~$eV up to more than $10^{20}~$eV. Measuring the independent contribution of the muon component to the total registered signal is crucial to enhance the capability of the Observatory to estimate the mass of the cosmic rays on an event-by-event basis. However, with the current design of the SD, it is difficult to straightforwardly separate the contributions of muons to the SD time traces from those of photons, electrons and positrons. In this paper, we present a method aimed at extracting the muon component of the time traces registered with each individual detector of the SD using Recurrent Neural Networks. We derive the performances of the method by training the neural network on simulations, in which the muon and the electromagnetic components of the traces are known. We conclude this work showing the performance of this method on experimental data of the Pierre Auger Observatory. We find that our predictions agree with the parameterizations obtained by the AGASA collaboration to describe the lateral distributions of the electromagnetic and muonic components of extensive air showers.Comment: 23 pages, 15 figures. Version accepted for publication in JINS

Design and implementation of the AMIGA embedded system for data acquisition

The Auger Muon Infill Ground Array (AMIGA) is part of the AugerPrime upgrade of the Pierre Auger Observatory. It consists of particle counters buried 2.3 m underground next to the water-Cherenkov stations that form the 23.5 km$^2$ large infilled array. The reduced distance between detectors in this denser area allows the lowering of the energy threshold for primary cosmic ray reconstruction down to about 10$^{17}$ eV. At the depth of 2.3 m the electromagnetic component of cosmic ray showers is almost entirely absorbed so that the buried scintillators provide an independent and direct measurement of the air showers muon content. This work describes the design and implementation of the AMIGA embedded system, which provides centralized control, data acquisition and environment monitoring to its detectors. The presented system was firstly tested in the engineering array phase ended in 2017, and lately selected as the final design to be installed in all new detectors of the production phase. The system was proven to be robust and reliable and has worked in a stable manner since its first deployment.Comment: Accepted for publication at JINST. Published version, 34 pages, 15 figures, 4 table

Design, upgrade and characterization of the silicon photomultiplier front-end for the AMIGA detector at the Pierre Auger Observatory

AMIGA (Auger Muons and Infill for the Ground Array) is an upgrade of the Pierre Auger Observatory to complement the study of ultra-high-energy cosmic rays (UHECR) by measuring the muon content of extensive air showers (EAS). It consists of an array of 61 water Cherenkov detectors on a denser spacing in combination with underground scintillation detectors used for muon density measurement. Each detector is composed of three scintillation modules, with 10 m$^2$ detection area per module, buried at 2.3 m depth, resulting in a total detection area of 30 m$^2$. Silicon photomultiplier sensors (SiPM) measure the amount of scintillation light generated by charged particles traversing the modules. In this paper, the design of the front-end electronics to process the signals of those SiPMs and test results from the laboratory and from the Pierre Auger Observatory are described. Compared to our previous prototype, the new electronics shows a higher performance, higher efficiency and lower power consumption, and it has a new acquisition system with increased dynamic range that allows measurements closer to the shower core. The new acquisition system is based on the measurement of the total charge signal that the muonic component of the cosmic ray shower generates in the detector.Comment: 40 pages, 33 figure

Deep-Learning based Reconstruction of the Shower Maximum XmaxX_{\mathrm{max}} using the Water-Cherenkov Detectors of the Pierre Auger Observatory

The atmospheric depth of the air shower maximum $X_{\mathrm{max}}$ is an observable commonly used for the determination of the nuclear mass composition of ultra-high energy cosmic rays. Direct measurements of $X_{\mathrm{max}}$ are performed using observations of the longitudinal shower development with fluorescence telescopes. At the same time, several methods have been proposed for an indirect estimation of $X_{\mathrm{max}}$ from the characteristics of the shower particles registered with surface detector arrays. In this paper, we present a deep neural network (DNN) for the estimation of $X_{\mathrm{max}}$. The reconstruction relies on the signals induced by shower particles in the ground based water-Cherenkov detectors of the Pierre Auger Observatory. The network architecture features recurrent long short-term memory layers to process the temporal structure of signals and hexagonal convolutions to exploit the symmetry of the surface detector array. We evaluate the performance of the network using air showers simulated with three different hadronic interaction models. Thereafter, we account for long-term detector effects and calibrate the reconstructed $X_{\mathrm{max}}$ using fluorescence measurements. Finally, we show that the event-by-event resolution in the reconstruction of the shower maximum improves with increasing shower energy and reaches less than $25~\mathrm{g/cm^{2}}$ at energies above $2\times 10^{19}~\mathrm{eV}$.Comment: Published version, 29 pages, 12 figure