A mixed-signal ASIC for timing and energy measurements with radiation detectors is described. The chip embeds 64 channels, each of which features a charge-sensitive amplifier followed by a ...dual-shaper coupled to low-offset discriminators. A versatile back-end, incorporating low-power Time to Digital Converters and Wilkinson Analog to Digital Converters with derandomizing buffers allows to encode both the time of arrival and the charge of the input signal. The ASIC is designed for a maximum detector capacitance of 100 pF and an event rate in excess of 60 kHz per channel. A peak detector samples the input signal with an excellent linearity in the range 5÷55 fC. Charge digitization with Time-over-Threshold is also supported to extend the dynamic range. Fabricated in a 110 nm CMOS process, the chip dissipates 10 mW/channel. The ASIC was primarily developed to readout the cylindrical GEM detector of the BESIII experiment. For its characteristics it can serve however a broad class of radiation sensors, including silicon microstrip detectors.
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•Range monitoring is necessary to fully exploit hadrontherapy advantages.•The Monte Carlo (MC) simulation tool for the INSIDE in-beam PET scanner is described.•The Monte Carlo tool ...provides images directly comparable with the experimental ones.•The comparison with in vivo experimental data validates the tool reliability.•The simulation information is already reliable after the first half of the treatment.
Hadrontherapy is a method for treating cancer with very targeted dose distributions and enhanced radiobiological effects. To fully exploit these advantages, in vivo range monitoring systems are required. These devices measure, preferably during the treatment, the secondary radiation generated by the beam-tissue interactions. However, since correlation of the secondary radiation distribution with the dose is not straightforward, Monte Carlo (MC) simulations are very important for treatment quality assessment.
The INSIDE project constructed an in-beam PET scanner to detect signals generated by the positron-emitting isotopes resulting from projectile-target fragmentation. In addition, a FLUKA-based simulation tool was developed to predict the corresponding reference PET images using a detailed scanner model.
The INSIDE in-beam PET was used to monitor two consecutive proton treatment sessions on a patient at the Italian Center for Oncological Hadrontherapy (CNAO). The reconstructed PET images were updated every 10 s providing a near real-time quality assessment. By half-way through the treatment, the statistics of the measured PET images were already significant enough to be compared with the simulations with average differences in the activity range less than 2.5 mm along the beam direction. Without taking into account any preferential direction, differences within 1 mm were found.
In this paper, the INSIDE MC simulation tool is described and the results of the first in vivo agreement evaluation are reported. These results have justified a clinical trial, in which the MC simulation tool will be used on a daily basis to study the compliance tolerances between the measured and simulated PET images.
Positron emission tomography is one of the most mature techniques for monitoring the particles range in hadron therapy, aiming to reduce treatment uncertainties and therefore the extent of safety ...margins in the treatment plan. In-beam PET monitoring has been already performed using inter-spill and post-irradiation data, i.e. while the particle beam is off or paused. The full beam acquisition procedure is commonly discarded because the particle spills abruptly increase the random coincidence rates and therefore the image noise. This is because random coincidences cannot be separated by annihilation photons originating from radioactive decays and cannot be corrected with standard random coincidence techniques due to the time correlation of the beam-induced background with the ion beam microstructure. The aim of this paper is to provide a new method to recover in-spill data to improve the images obtained with full-beam PET acquisitions. This is done by estimating the temporal microstructure of the beam and thus selecting input PET events that are less likely to be random ones. The PET detector we used was the one developed within the INSIDE project and tested at the CNAO synchrotron-based facility. The data were taken on a PMMA phantom irradiated with 72 MeV proton pencil beams. The obtained results confirm the possibility of improving the acquired PET data without any external signal coming from the synchrotron or ad hoc detectors.
Populations around the world are aging rapidly. Age-related loss of physiological functions negatively affects quality of life. A major contributor to the frailty syndrome of aging is loss of ...skeletal muscle. In this study we assessed the skeletal muscle biopsy metabolome of healthy young, healthy older and frail older subjects to determine the effect of age and frailty on the metabolic signature of skeletal muscle tissue. In addition, the effects of prolonged whole-body resistance-type exercise training on the muscle metabolome of older subjects were examined. The baseline metabolome was measured in muscle biopsies collected from 30 young, 66 healthy older subjects, and 43 frail older subjects. Follow-up samples from frail older (24 samples) and healthy older subjects (38 samples) were collected after 6 months of prolonged resistance-type exercise training. Young subjects were included as a reference group. Primary differences in skeletal muscle metabolite levels between young and healthy older subjects were related to mitochondrial function, muscle fiber type, and tissue turnover. Similar differences were observed when comparing frail older subjects with healthy older subjects at baseline. Prolonged resistance-type exercise training resulted in an adaptive response of amino acid metabolism, especially reflected in branched chain amino acids and genes related to tissue remodeling. The effect of exercise training on branched-chain amino acid-derived acylcarnitines in older subjects points to a downward shift in branched-chain amino acid catabolism upon training. We observed only modest correlations between muscle and plasma metabolite levels, which pleads against the use of plasma metabolites as a direct read-out of muscle metabolism and stresses the need for direct assessment of metabolites in muscle tissue biopsies.
Objective: The study objective was to determine whether adequately delivered bilateral remote ischemic preconditioning is cardioprotective in young children undergoing surgery for 2 common congenital ...heart defects with or without cyanosis. Methods: We performed a prospective, double-blind, randomized controlled trial at 2 centers in the United Kingdom. Children aged 3 to 36 months undergoing tetralogy of Fallot repair or ventricular septal defect closure were randomized 1:1 to receive bilateral preconditioning or sham intervention. Participants were followed up until hospital discharge or 30 days. The primary outcome was area under the curve for high-sensitivity troponin-T in the first 24 hours after surgery, analyzed by intention-to-treat. Right atrial biopsies were obtained in selected participants. Results: Between October 2016 and December 2020, 120 eligible children were randomized to receive bilateral preconditioning (n = 60) or sham intervention (n = 60). The primary outcome, area under the curve for high-sensitivity troponin-T, was higher in the preconditioning group (mean: 70.0 ± 50.9 μg/L/h, n = 56) than in controls (mean: 55.6 ± 30.1 μg/L/h, n = 58) (mean difference, 13.2 μg/L/h; 95% CI, 0.5-25.8; P = .04). Subgroup analyses did not show a differential treatment effect by oxygen saturations (pinteraction = .25), but there was evidence of a differential effect by underlying defect (pinteraction = .04). Secondary outcomes and myocardial metabolism, quantified in atrial biopsies, were not different between randomized groups. Conclusions: Bilateral remote ischemic preconditioning does not attenuate myocardial injury in children undergoing surgical repair for congenital heart defects, and there was evidence of potential harm in unstented tetralogy of Fallot. The routine use of remote ischemic preconditioning cannot be recommended for myocardial protection during pediatric cardiac surgery.
Abstract Aria is a plant hosting a $${350}\,\hbox {m}$$ 350 m cryogenic isotopic distillation column, the tallest ever built, which is being installed in a mine shaft at Carbosulcis S.p.A., ...Nuraxi-Figus (SU), Italy. Aria is one of the pillars of the argon dark-matter search experimental program, lead by the Global Argon Dark Matter Collaboration. It was designed to reduce the isotopic abundance of $${^{39}\hbox {Ar}}$$ 39 Ar in argon extracted from underground sources, called Underground Argon (UAr), which is used for dark-matter searches. Indeed, $${^{39}\hbox {Ar}}$$ 39 Ar is a $$\beta $$ β -emitter of cosmogenic origin, whose activity poses background and pile-up concerns in the detectors. In this paper, we discuss the requirements, design, construction, tests, and projected performance of the plant for the isotopic cryogenic distillation of argon. We also present the successful results of the isotopic cryogenic distillation of nitrogen with a prototype plant.
The CERN RD53 collaboration was founded to tackle the extraordinary challenges associated with the design of pixel readout chips for the innermost layers of particle trackers at future high energy ...physics experiments. Around 20 institutions are involved in the collaboration, which has the support of both ATLAS and CMS experiments. The goals of the collaboration include the comprehensive understanding of radiation effects in the 65 nm technology, the development of tools and methodology to efficiently design large complex mixed signal chips and, ultimately, the development of a full size readout chip featuring a 400 × 400 pixel array with 50μm pitch. In August 2017, the collaboration submitted the large scale chip RD53A, integrating a matrix of 400 × 192 pixels and embodying three different analog front-end designs. This work discusses the characteristic of the RD53A chip, with some emphasis on the analog processors, and presents the first test results on the pixel array.
•High particle rates and radiation levels will be reached at the HL-LHC.•New pixel chips for the phase II upgrades of CMS and ATLAS are required.•The RD53A chip has been designed in the framework of the RD53 Collaboration.•Three analog front-ends flavors are integrated in RD53A.•The paper presents the main preliminary results coming from RD53A characterization.
Ever since eukaryotes subsumed the bacterial ancestor of mitochondria, the nuclear and mitochondrial genomes have had to closely coordinate their activities, as each encode different subunits of the ...oxidative phosphorylation (OXPHOS) system. Mitochondrial dysfunction is a hallmark of aging, but its causes are debated. We show that, during aging, there is a specific loss of mitochondrial, but not nuclear, encoded OXPHOS subunits. We trace the cause to an alternate PGC-1α/β-independent pathway of nuclear-mitochondrial communication that is induced by a decline in nuclear NAD+ and the accumulation of HIF-1α under normoxic conditions, with parallels to Warburg reprogramming. Deleting SIRT1 accelerates this process, whereas raising NAD+ levels in old mice restores mitochondrial function to that of a young mouse in a SIRT1-dependent manner. Thus, a pseudohypoxic state that disrupts PGC-1α/β-independent nuclear-mitochondrial communication contributes to the decline in mitochondrial function with age, a process that is apparently reversible.
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•A specific decline in mitochondrially encoded genes occurs during aging in muscle•Nuclear NAD+ levels regulate mitochondrial homeostasis independently of PGC-1α/β•Declining NAD+ during aging causes pseudohypoxia, which disrupts OXPHOS function•Raising nuclear NAD+ in old mice reverses pseudohypoxia and metabolic dysfunction
Aging disrupts an NAD+-dependent nuclear-mitochondrial communication pathway, causing a decline in the mitochondrially encoded oxidative phosphorylation components relative to nuclear-encoded components. Raising NAD+ levels in old mice alleviates the pseudohypoxic conditions that disrupt the communication pathway, reversing this mitochondrial defect.
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