Influence of the background in Compton camera images for proton therapy treatment monitoring.

Objective. Background events are one of the most relevant contributions to image degradation in Compton camera imaging for hadron therapy treatment monitoring. A study of the background and its contribution to image degradation is important to define future strategies to reduce the background in the system.Approach. In this simulation study, the percentage of different kinds of events and their contribution to the reconstructed image in a two-layer Compton camera have been evaluated. To this end, GATE v8.2 simulations of a proton beam impinging on a PMMA phantom have been carried out, for different proton beam energies and at different beam intensities.Main results. For a simulated Compton camera made of Lanthanum (III) Bromide monolithic crystals, coincidences caused by neutrons arriving from the phantom are the most common type of background produced by secondary radiations in the Compton camera, causing between 13% and 33% of the detected coincidences, depending on the beam energy. Results also show that random coincidences are a significant cause of image degradation at high beam intensities, and their influence in the reconstructed images is studied for values of the time coincidence windows from 500 ps to 100 ns.Significance. Results indicate the timing capabilities required to retrieve the fall-off position with good precision. Still, the noise observed in the image when no randoms are considered make us consider further background rejection methods.

Joint image reconstruction algorithm in Compton cameras.

Objective.To demonstrate the benefits of using an joint image reconstruction algorithm based on the List Mode Maximum Likelihood Expectation Maximization that combines events measured in different channels of information of a Compton camera.Approach.Both simulations and experimental data are employed to show the algorithm performance.Main results.The obtained joint images present improved image quality and yield better estimates of displacements of high-energy gamma-ray emitting sources. The algorithm also provides images that are more stable than any individual channel against the noisy convergence that characterizes Maximum Likelihood based algorithms.Significance.The joint reconstruction algorithm can improve the quality and robustness of Compton camera images. It also has high versatility, as it can be easily adapted to any Compton camera geometry. It is thus expected to represent an important step in the optimization of Compton camera imaging.

First Search for Dyons with the Full MoEDAL Trapping Detector in 13 TeV pp Collisions.

The MoEDAL trapping detector consists of approximately 800 kg of aluminum volumes. It was exposed during run 2 of the LHC program to 6.46 fb^{-1} of 13 TeV proton-proton collisions at the LHCb interaction point. Evidence for dyons (particles with electric and magnetic charge) captured in the trapping detector was sought by passing the aluminum volumes comprising the detector through a superconducting quantum interference device (SQUID) magnetometer. The presence of a trapped dyon would be signaled by a persistent current induced in the SQUID magnetometer. On the basis of a Drell-Yan production model, we exclude dyons with a magnetic charge ranging up to five Dirac charges (5g_{D}) and an electric charge up to 200 times the fundamental electric charge for mass limits in the range 870-3120 GeV and also monopoles with magnetic charge up to and including 5g_{D} with mass limits in the range 870-2040 GeV.

Image reconstruction for a multi-layer Compton telescope: an analytical model for three interaction events.

Compton Cameras are electronically collimated photon imagers suitable for sub-MeV to few MeV gamma-ray detection. Such features are desirable to enable in vivo range verification in hadron therapy, through the detection of secondary Prompt Gammas. A major concern with this technique is the poor image quality obtained when the incoming gamma-ray energy is unknown. Compton Cameras with more than two detector planes (multi-layer Compton Cameras) have been proposed as a solution, given that these devices incorporate more signal sequences of interactions to the conventional two interaction events. In particular, three interaction events convey more spectral information as they allow inferring directly the incident gamma-ray energy. A three-layer Compton Telescope based on continuous Lanthanum (III) Bromide crystals coupled to Silicon Photomultipliers is being developed at the IRIS group of IFIC-Valencia. In a previous work we proposed a spectral reconstruction algorithm for two interaction events based on an analytical model for the formation of the signal. To fully exploit the capabilities of our prototype, we present here an extension of the model for three interaction events. Analytical expressions of the sensitivity and the System Matrix are derived and validated against Monte Carlo simulations. Implemented in a List Mode Maximum Likelihood Expectation Maximization algorithm, the proposed model allows us to obtain four-dimensional (energy and position) images by using exclusively three interaction events. We are able to recover the correct spectrum and spatial distribution of gamma-ray sources when ideal data are employed. However, the uncertainties associated to experimental measurements result in a degradation when real data from complex structures are employed. Incorrect estimation of the incident gamma-ray interaction positions, and missing deposited energy associated with escaping secondaries, have been identified as the causes of such degradation by means of a detailed Monte Carlo study. As expected, our current experimental resolution and efficiency to three interaction events prevents us from correctly recovering complex structures of radioactive sources. However, given the better spectral information conveyed by three interaction events, we expect an improvement of the image quality of conventional Compton imaging when including such events. In this regard, future development includes the incorporation of the model assessed in this work to the two interaction events model in order to allow using simultaneously two and three interaction events in the image reconstruction.

Magnetic Monopole Search with the Full MoEDAL Trapping Detector in 13 TeV pp Collisions Interpreted in Photon-Fusion and Drell-Yan Production.

MoEDAL is designed to identify new physics in the form of stable or pseudostable highly ionizing particles produced in high-energy Large Hadron Collider (LHC) collisions. Here we update our previous search for magnetic monopoles in Run 2 using the full trapping detector with almost four times more material and almost twice more integrated luminosity. For the first time at the LHC, the data were interpreted in terms of photon-fusion monopole direct production in addition to the Drell-Yan-like mechanism. The MoEDAL trapping detector, consisting of 794 kg of aluminum samples installed in the forward and lateral regions, was exposed to 4.0 fb^{-1} of 13 TeV proton-proton collisions at the LHCb interaction point and analyzed by searching for induced persistent currents after passage through a superconducting magnetometer. Magnetic charges equal to or above the Dirac charge are excluded in all samples. Monopole spins 0, ½, and 1 are considered and both velocity-independent and-dependent couplings are assumed. This search provides the best current laboratory constraints for monopoles with magnetic charges ranging from two to five times the Dirac charge.

Search for Magnetic Monopoles with the MoEDAL Forward Trapping Detector in 13 TeV Proton-Proton Collisions at the LHC.

MoEDAL is designed to identify new physics in the form of long-lived highly ionizing particles produced in high-energy LHC collisions. Its arrays of plastic nuclear-track detectors and aluminium trapping volumes provide two independent passive detection techniques. We present here the results of a first search for magnetic monopole production in 13 TeV proton-proton collisions using the trapping technique, extending a previous publication with 8 TeV data during LHC Run 1. A total of 222 kg of MoEDAL trapping detector samples was exposed in the forward region and analyzed by searching for induced persistent currents after passage through a superconducting magnetometer. Magnetic charges exceeding half the Dirac charge are excluded in all samples and limits are placed for the first time on the production of magnetic monopoles in 13 TeV pp collisions. The search probes mass ranges previously inaccessible to collider experiments for up to five times the Dirac charge.

Hemocromatosis neonatal: otra entidad que deja de ser huérfana. Avances en el diagnóstico y manejo de la principal causa de fallo hepático agudo neonatal / Neonatal hemochromatosis: Another entity that is no longer orphan. Advances in the diagnosis and management of the main cause of neonatal acute liver failure

La hemocromatosis neonatal es la causa más frecuente de fallo hepático agudo en el periodo neonatal. Asocia una elevada morbimortalidad dado el daño hepático secundario a acúmulo de hierro. En los últimos años, las nuevas evidencias acerca de su etiopatogenia aloinmune han repercutido sobre el diagnóstico, el tratamiento y el pronóstico de estos pacientes. El tratamiento con gammaglobulinas y exsanguinotransfusión ha cambiado radicalmente el pronóstico libre de trasplante. Otro gran éxito ha sido el uso preventivo de gammaglobulina en las gestantes con antecedentes de hemocromatosis neonatal, disminuyendo así la tasa de recurrencia de la enfermedad de hasta un 70%. Este nuevo paradigma ha convertido a una entidad con un pobre pronóstico en una patología con posibilidad de curación si se diagnostica y trata precozmente. A pesar de ello, sigue habiendo un gran desconocimiento generalizado de la enfermedad, con implicaciones médicas que derivan en un importante problema sanitario, ya que estos pacientes se derivan de forma tardía a los centros especializados

Neonatal hemochromatosis is the most common cause of acute liver failure in the neonatal period. It is associated with high morbidity and mortality due to iron overload in hepatic and extra-hepatic tissues. New evidence has emerged during the last few years as regards its alloimmune etiology, which have had an important repercussion on the diagnosis, treatment and prognosis of these patients. Treatment with immunoglobulins and exchange transfusions has radically changed the prognosis without liver transplant. Another great success has been the preventive use of immunoglobulin in pregnant women with a past history of neonatal hemochromatosis, thus decreasing the rate of disease recurrence up to 70%. This new paradigm has led to an entity with a poor prognosis becoming a curable disease if diagnosed and treated early. Nevertheless, a large widespread ignorance of the disease persists, with medical implications that result in significant health problems, due to the delayed referral of these patients to specialized centers

[Neonatal hemochromatosis: Another entity that is no longer orphan. Advances in the diagnosis and management of the main cause of neonatal acute liver failure]. / Hemocromatosis neonatal: otra entidad que deja de ser huérfana. Avances en el diagnóstico y manejo de la principal causa de fallo hepático agudo neonatal.

Neonatal hemochromatosis is the most common cause of acute liver failure in the neonatal period. It is associated with high morbidity and mortality due to iron overload in hepatic and extra-hepatic tissues. New evidence has emerged during the last few years as regards its alloimmune etiology, which have had an important repercussion on the diagnosis, treatment and prognosis of these patients. Treatment with immunoglobulins and exchange transfusions has radically changed the prognosis without liver transplant. Another great success has been the preventive use of immunoglobulin in pregnant women with a past history of neonatal hemochromatosis, thus decreasing the rate of disease recurrence up to 70%. This new paradigm has led to an entity with a poor prognosis becoming a curable disease if diagnosed and treated early. Nevertheless, a large widespread ignorance of the disease persists, with medical implications that result in significant health problems, due to the delayed referral of these patients to specialized centers.

Síndrome radiológico aislado / Radiologically isolated syndrome

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Utilización de levetiracetam intravenoso en un hospital general / The Use of intravenous levetiracetam in a general hospital

Introducción y objetivos. Aunque la vía oral es la forma habitual de administración de los fármacos antiepilépticos, en ciertas ocasiones se requiere la vía parenteral. El levetiracetam es el único de los nuevos fármacos antiepilépticos con posibilidad de administración por vía intravenosa. Se presenta un estudio de utilización de levetiracetam intravenoso en un hospital general, con evaluación de su eficacia y seguridad. Pacientes y métodos. Se analizaron de forma retrospectiva las historias clínicas de todos los pacientes ingresados en el hospital que fueron tratados con levetiracetam intravenoso durante el período de tiempo comprendido entre julio de 2007 y mayo de 2008. Resultados. Un total de 53 pacientes fue tratado con levetiracetam intravenoso. Aproximadamente la mitad de los pacientes (47%) había estado ingresada a cargo del servicio de neurología, seguido del servicio de neurocirugía (21%) y oncología (9%). La edad media fue de 52,2 años (rango: 9-87 años) y el 40% eran mujeres. Las crisis fueron sintomáticas en el 81%, y las etiologías más frecuentes fueron los ictus (40%) y los tumores cerebrales (33%). La presentación clínica más frecuente fueron las crisis epilépticas repetidas (47,2%) y el estado epiléptico (26,4%). Globalmente, el control de las crisis se consiguió en el 87% de los pacientes. No se detectaron efectos adversos graves atribuibles al tratamiento con levetiracetam. Conclusiones. El levetiracetam intravenoso parece ser un fármaco antiepiléptico eficaz y seguro en pacientes hospitalizados, especialmente en aquéllos que presentan comorbilidad asociada y/o plurimedicación (AU)

Introduction and aims. Although antiepileptic drugs are usually administered orally, sometimes they must be given intravenously. Levetiracetam is the only one of the new antiepileptic drugs that can be administered intravenously. In this study we report on the use of intravenous levetiracetam in a general hospital, while also evaluating its effectiveness and safety. Patients and methods. A retrospective analysis was conducted of the medical records of all hospital admissions that were treated with intravenous levetiracetam between July 2007 and May 2008. Results. A total of 53 patients were treated with intravenous levetiracetam. Approximately half the patients (47%) had been admitted to neurology, followed by neurosurgery (21%) and oncology (9%). The mean age was 52.2 years (range: 9-87 years) and 40% were females. Seizures were symptomatic in 81% of cases and the most common aetiologies were strokes (40%) and brain tumours (33%). The most frequent presenting symptoms were repeated epileptic seizures (47.2%) and epileptic status (26.4%). Overall, control of seizures was achieved in 87% of patients. No severe side-effects that could be attributed to levetiracetam therapy were detected. Conclusions. Intravenous levetiracetam seems to be an effective, safe antiepileptic drug in hospitalised patients, and especially so in those who present an associated comorbidity and/or who are on multiple drug therapy (AU)

[The use of intravenous levetiracetam in a general hospital]. / Utilización de levetiracetam intravenoso en un hospital general.

INTRODUCTION AND AIMS: Although antiepileptic drugs are usually administered orally, sometimes they must be given intravenously. Levetiracetam is the only one of the new antiepileptic drugs that can be administered intravenously. In this study we report on the use of intravenous levetiracetam in a general hospital, while also evaluating its effectiveness and safety. PATIENTS AND METHODS: A retrospective analysis was conducted of the medical records of all hospital admissions that were treated with intravenous levetiracetam between July 2007 and May 2008. RESULTS: A total of 53 patients were treated with intravenous levetiracetam. Approximately half the patients (47%) had been admitted to neurology, followed by neurosurgery (21%) and oncology (9%). The mean age was 52.2 years (range: 9-87 years) and 40% were females. Seizures were symptomatic in 81% of cases and the most common aetiologies were strokes (40%) and brain tumours (33%). The most frequent presenting symptoms were repeated epileptic seizures (47.2%) and epileptic status (26.4%). Overall, control of seizures was achieved in 87% of patients. No severe side-effects that could be attributed to levetiracetam therapy were detected. CONCLUSIONS: Intravenous levetiracetam seems to be an effective, safe antiepileptic drug in hospitalised patients, and especially so in those who present an associated comorbidity and/or who are on multiple drug therapy.

Duplication of the Williams-Beuren critical region: case report and further delineation of the phenotypic spectrum.

Only 12 patients with a duplication of the Williams-Beuren critical region (WBCR) have been reported to date, with variable developmental, psychomotor and language delay, in the absence of marked dysmorphic features. In this paper we present a new WBCR microduplication case, which supports the wide variability displayed by this duplication in the phenotype. The WBCR microduplication may be associated with autistic spectrum disorder, but most reported cases do not show this behavioural disorder, or may even show a hypersociable personality, as with our patient. From the present case and a review of the 12 previously described, we conclude that the phenotype associated with duplication of WBCR can affect the same domains as WBCR deletion, but that they cluster near the polar ends of social relationship (autism-like v hypersociability), language (expressive language impairment v "cocktail party" speech), visuospatial (severe v normal), mental retardation (severe v mild) and dysmorphic (severe v mild) features.

Trastorno del sueño asociado al tratamiento con rimonabant / Sleep disorders associated with treatment with rimonabant

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Statistical method for evaluation of dissolution stability in the formulation development of solid dosage forms: tablets of amonafide.

A statistical method for the evaluation of the dissolution stability results and for selecting the most stable formulation within a solid dosage form development is discussed. Three types of tablets of an antineoplastic drug, amonafide, stored at a relative humidities (RH), 45% and 75%, were used. The drug release from tablets was tested before and after storage. The experimental data were statistically fitted to empirical model equations. Furthermore, the best mathematical fit was the statistical comparison of the residuals. From the selected model equation, time-dependent dissolution (Q45 and DE45) and dissolved quantity-dependent parameters (t70, t100 and MDT) were calculated. A useful parameter to present and evaluate the results obtained in comparative stability studies was defined: the Modification Factor (MF). It allowed the selection of the most stable formulation in the easiest and fastest way: the most stable formulation should present the smallest modification of the studied characteristics, in other words, the smallest MF value. In this way, tablets II (manufactured by wet granulation and with Emcompress as main excipient) showed the greater dissolution stability of the three types of tablets studied. Amonafide tablets must be packaged in impermeable containers, since the environmental relative humidity strongly modifies their dissolution characteristics.