Background
Dose calculations for novel radiotherapy cancer treatments such as proton minibeam radiation therapy is often done using full Monte Carlo (MC) simulations. As MC simulations can be very ...time consuming for this kind of application, deep learning models have been considered to accelerate dose estimation in cancer patients.
Purpose
This work systematically evaluates the dose prediction accuracy, speed and generalization performance of three selected state‐of‐the‐art deep learning models for dose prediction applied to the proton minibeam therapy. The strengths and weaknesses of those models are thoroughly investigated, helping other researchers to decide on a viable algorithm for their own application.
Methods
The following recently published models are compared: first, a 3D U‐Net model trained as a regression network, second, a 3D U‐Net trained as a generator of a generative adversarial network (GAN) and third, a dose transformer model which interprets the dose prediction as a sequence translation task. These models are trained to emulate the result of MC simulations. The dose depositions of a proton minibeam with a diameter of 800μm and an energy of 20–100 MeV inside a simple head phantom calculated by full Geant4 MC simulations are used as a case study for this comparison. The spatial resolution is 0.5 mm. Special attention is put on the evaluation of the generalization performance of the investigated models.
Results
Dose predictions with all models are produced in the order of a second on a GPU, the 3D U‐Net models being fastest with an average of 130 ms. An investigated 3D U‐Net regression model is found to show the strongest performance with overall 61.0%±$\%\pm$0.5% of all voxels exhibiting a deviation in energy deposition prediction of less than 3% compared to full MC simulations with no spatial deviation allowed. The 3D U‐Net models are observed to show better generalization performance for target geometry variations, while the transformer‐based model shows better generalization with regard to the proton energy.
Conclusions
This paper reveals that (1) all studied deep learning models are significantly faster than non‐machine learning approaches predicting the dose in the order of seconds compared to hours for MC, (2) all models provide reasonable accuracy, and (3) the regression‐trained 3D U‐Net provides the most accurate predictions.
Abstract
Objective.
Due to the radiosensitizing effect of biocompatible noble metal nanoparticles (NPs), their administration is considered to potentially increase tumor control in radiotherapy. The ...underlying physical, chemical and biological mechanisms of the NPs’ radiosensitivity especially when interacting with proton radiation is not conclusive. In the following work, the energy deposition of protons in matter containing platinum nanoparticles (PtNPs) is experimentally investigated.
Approach.
Surfactant-free monomodal PtNPs with a mean diameter of (40 ± 10) nm and a concentration of 300 μg ml
−1
, demonstrably leading to a substantial production of reactive oxygen species (ROS), were homogeneously dispersed into cubic gelatin samples serving as tissue-like phantoms. Gelatin samples without PtNPs were used as control. The samples’ dimensions and contrast of the PtNPs were verified in a clinical computed tomography scanner. Fields from a clinical proton machine were used for depth dose and stopping power measurements downstream of both samples types. These experiments were performed with a variety of detectors at a pencil beam scanning beam line as well as a passive beam line with proton energies from about 56–200 MeV.
Main results.
The samples’ water equivalent ratios in terms of proton stopping as well as the mean proton energy deposition downstream of the samples with ROS-producing PtNPs compared to the samples without PtNPs showed no differences within the experimental uncertainties of about 2%.
Significance.
This study serves as experimental proof that the radiosensitizing effect of biocompatible PtNPs is not due to a macroscopically increased proton energy deposition, but is more likely caused by a catalytic effect of the PtNPs. Thus, these experiments provide a contribution to the highly discussed radiobiological question of the proton therapy efficiency with noble metal NPs and facilitate initial evidence that the dose calculation in treatment planning is straightforward and not affected by the presence of sensitizing PtNPs.
Auditory brainstem neurons in the lateral superior olive (LSO) receive excitatory input from the ipsilateral cochlear nucleus (CN) and inhibitory transmission from the contralateral CN via the medial ...nucleus of the trapezoid body (MNTB). This circuit enables sound localization using interaural level differences. Early studies have observed an additional inhibitory input originating from the ipsilateral side. However, many of its details, such as its origin, remained elusive. Employing electrical and optical stimulation of afferents in acute mouse brainstem slices and anatomical tracing, we here describe a glycinergic projection to LSO principal neurons that originates from the ipsilateral CN. This inhibitory synaptic input likely mediates inhibitory sidebands of LSO neurons in response to acoustic stimulation.
Abstract
Background
Acute pancreatitis (AP) is an inflammatory disorder that causes a considerable economic health burden. While the overall mortality is low, around 20% of patients have a ...complicated course of disease resulting in increased morbidity and mortality. There is an emerging body of evidence that the microbiome exerts a crucial impact on the pathophysiology and course of AP. For several decades multiple clinical and laboratory parameters have been evaluated, and complex scoring systems were developed to predict the clinical course of AP upon admission. However, the majority of scoring systems are determined after several days and achieve a sensitivity around 70% for early prediction of severe AP. Thus, continued efforts are required to investigate reliable biomarkers for the early prediction of severity in order to guide early clinical management of AP patients.
Methods
We designed a multi-center, prospective clinical-translational study to test whether the orointestinal microbiome may serve as novel early predictor of the course, severity and outcome of patients with AP. We will recruit 400 AP patients and obtain buccal and rectal swabs within 72 h of admission to the hospital. Following DNA extraction, microbiome analysis will be performed using 3rd generation sequencing Oxford Nanopore Technologies (ONT) for 16S rRNA and metagenomic sequencing. Alpha- and beta-diversity will be determined and correlated to the revised Atlanta classification and additional clinical outcome parameters such as the length of hospital stay, number and type of complications, number of interventions and 30-day mortality.
Discussion
If AP patients show a distinct orointestinal microbiome dependent on the severity and course of the disease, microbiome sequencing could rapidly be implemented in the early clinical management of AP patients in the future.
Trial registration
: ClinicalTrials.gov Identifier: NCT04777812
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The upgrade of the ATLAS detector will undergo different phases towards high luminosity LHC. The first upgrade for the Pixel Detector will consist in the construction of a new pixel layer which will ...be installed during the first shutdown of the LHC machine (foreseen for 2013-14). The new detector, called Insertable B-Layer (IBL), will be inserted between the existing Pixel Detector and a new (smaller radius) beam-pipe at a radius of 3.2 cm. The IBL will require the development of several new technologies to cope with increase of radiation or pixel occupancy and also to improve the physics performance which will be achieved by reduction of the pixel size and of the material budget. Two different promising Silicon sensor technologies (Planar n-in-n and 3D) are currently under investigation for the Pixel Detector. An overview of the sensor technologies qualification with particular emphasis on irradiation and beam tests will be presented.
Astrocytes form large gap junctional networks that contribute to ion and neurotransmitter homeostasis. Astrocytes concentrate in the lateral superior olive (LSO), a prominent auditory brainstem ...center. Compared to the LSO, astrocyte density is lower in the region dorsal to the LSO (dLSO) and in the internuclear space between the LSO, the superior paraolivary nucleus (SPN). We questioned whether astrocyte networks exhibit certain properties that reflect the precise neuronal arrangement. Employing whole‐cell patch‐clamp and concomitant injection of a gap junction‐permeable tracer, we analyzed size and orientation of astrocyte networks in LSO, dLSO, and SPN‐LSO in acute brainstem slices of mice at postnatal days 10–20. The majority of LSO networks exhibited an oval topography oriented orthogonally to the tonotopic axis, whereas dLSO networks showed no preferred orientation. This correlated with the overall astrocyte morphology in both regions, i.e. LSO astrocyte processes were oriented mainly orthogonally to the tonotopic axis. To assess the spread of small ions within LSO networks, we analyzed the diffusion of Na+ signals between cells using Na+ imaging. We found that Na+ not only diffused between SR101+ astrocytes, but also from astrocytes into SR101− cells. Using PLP‐GFP mice for tracing, we could show that LSO networks contained astrocytes and oligodendrocytes. Together, our results demonstrate that LSO astrocytes and LSO oligodendrocytes form functional anisotropic panglial networks that are oriented predominantly orthogonally to the tonotopic axis. Thus, our results point toward an anisotropic ion and metabolite diffusion and a limited glial crosstalk between neighboring isofrequency bands in the LSO. GLIA 2016;64:1892–1911
Main Points
Lateral superior olive networks are anisotropic and oriented orthogonal to the tonotopic axis.
Networks contained astrocytes and oligodendrocytes.
Network anisotropy limits presumably glial crosstalk between neighboring isofrequency bands.
Immune thrombocytopenic purpura (ITP) is a rare autoimmune disorder that involves platelet destruction in the spleen. Eltrombopag (Promacta®), a thrombopoietin agonist, has been used in non-pregnant ...patients to manage ITP, but few cases of its use in pregnancy have been reported.
We present a case of a pregnant patient at 26 weeks of gestation with severe refractory ITP. After first-line therapies failed, the patient was treated with the drug eltrombopag. The patient had no response to initial therapy, and the fetus developed supraventricular tachycardia (SVT). This resolved with maternal digoxin but the patient elected to stop the eltrombopag. The patient refused further experimental and second-line treatments, and after a multidisciplinary meeting a decision was made to deliver by cesarean section at 30 weeks of gestation due to severe refractory ITP and allow other therapies to be tried postpartum. Preeclampsia and neonatal atrial flutter were encountered in the postpartum period but both mother and baby had good outcomes.
Refractory ITP in pregnancy is not well studied. Eltrombobag could have maternal and fetal side-effects but a multidisciplinary approach to management leads to favorable maternal and fetal outcomes.
•Eltrombopag is a second-line agent for treatment of refractory immune thrombocytopenia that is not well studied in pregnancy.•Fetal side-effects of eltrombopag use have not been established in pregnancy, but low birthweight has been reported.•Fetal supraventricular tachycardia is a possible side-effect of eltrombopag that we saw, but was safely treated with maternal digoxin.•Preeclampsia has been reported with eltrombopag use, as in this case, and the association needs to be further investigated.•Risks and benefits must be weighed for eltrombopag use and timing of delivery in cases of severe refractory immune thrombocytopenia.
The time- or temperature-resolved detector signal from a thermoluminescence dosimeter can reveal additional information about circumstances of an exposure to ionising irradiation. We present studies ...using deep neural networks to estimate the date of a single irradiation with 12 mSv within a monitoring interval of 42 days from glow curves of novel TL-DOS personal dosimeters developed by the Materialprüfungsamt NRW in cooperation with TU Dortmund University. Using a deep convolutional network, the irradiation date can be predicted from raw time-resolved glow curve data with an uncertainty of roughly 1-2 days on a 68% confidence level without the need for a prior transformation into temperature space and a subsequent glow curve deconvolution (GCD). This corresponds to a significant improvement in prediction accuracy compared to a prior publication, which yielded a prediction uncertainty of 2-4 days using features obtained from a GCD as input to a neural network.
The value of the scaling parameter Eeff of the temperature dependence for current generated in silicon bulk is investigated for highly irradiated devices. Measurements of devices irradiated to ...fluences above 1×1015neqcm-2 have shown a different temperature scaling behaviour than devices irradiated to lower fluences. This paper presents the determination of the parameter Eeff for diodes irradiated with protons up to fluences of 3×1015 neqcm-2 in the bias range from 0 V to 1000 V at temperatures from −36° to 0° at different stages of annealing. It is shown that Eeff for highly irradiated devices depends on the applied electric field: below depletion voltage, Eeff is observed to have a lower value than above depletion voltage.
Sustained neuronal activity demands a rapid resupply of synaptic vesicles to maintain reliable synaptic transmission. Such vesicle replenishment is accelerated by submicromolar presynaptic Ca
signals ...by an as-yet unidentified high-affinity Ca
sensor
. Here we identify synaptotagmin-3 (SYT3)
as that presynaptic high-affinity Ca
sensor, which drives vesicle replenishment and short-term synaptic plasticity. Synapses in Syt3 knockout mice exhibited enhanced short-term depression, and recovery from depression was slower and insensitive to presynaptic residual Ca
. During sustained neuronal firing, SYT3 accelerated vesicle replenishment and increased the size of the readily releasable pool. SYT3 also mediated short-term facilitation under conditions of low release probability and promoted synaptic enhancement together with another high-affinity synaptotagmin, SYT7 (ref.
). Biophysical modelling predicted that SYT3 mediates both replenishment and facilitation by promoting the transition of loosely docked vesicles to tightly docked, primed states. Our results reveal a crucial role for presynaptic SYT3 in the maintenance of reliable high-frequency synaptic transmission. Moreover, multiple forms of short-term plasticity may converge on a mechanism of reversible, Ca
-dependent vesicle docking.
PDF
