Silica-based scintillators: basic properties of radioluminescence kinetics.

Radioluminescent silica-based fiber dosimeters offer great advantages for designing miniaturized realtime sensors for high dose-rate dosimetry. Rise and fall kinetics of their response must be properly understood to better assess their performances in terms of measurement speed and repeatability. A standard model of radioluminescence (RL) has already been quantitatively validated for doped silica glasses, but beyond conclusive comparisons with specific experiments, a comprehensive understanding of the processes and parameters determining transient and equilibrium kinetics of RL is still lacking. We analyze in detail the kinetics inherent in the standard RL model. Several asymptotical regimes in the RL growth are demonstrated in the case of a pristine sample (succesive quadratic, linear and power-law time dependencies before the plateau is reached). We show how this situation is modified when a pre-irradiation partly fills traps beforehand. RL growth is then greatly accelerated because of the pre-formation of recombination centers (RCs) from dopant ions, but not due to pre-filling of trapping levels. In all cases, the RL intensity eventually tends to a constant level equal to the pair generation rate, long before all carrier densities themselves reach equilibrium. This occurs late under irradiation, when deep traps get to saturation. The fraction of dopants converted into RCs is then 'frozen' at a lower level the smaller the density of deep traps. Controlling RL kinetics through the engineering of material traps is not an option. Pre-irradiation appears to be the simplest way to obtain accelerated and repeatable kinetics.

Exploring a targeted approach for public health capacity restrictions during COVID-19 using a new computational model.

This work introduces the Queen's University Agent-Based Outbreak Outcome Model (QUABOOM). This tool is an agent-based Monte Carlo simulation for modelling epidemics and informing public health policy. We illustrate the use of the model by examining capacity restrictions during a lockdown. We find that public health measures should focus on the few locations where many people interact, such as grocery stores, rather than the many locations where few people interact, such as small businesses. We also discuss a case where the results of the simulation can be scaled to larger population sizes, thereby improving computational efficiency.

Beam monitor chamber calibration of a synchro-cyclotron high dose rate per pulse pulsed scanned proton beam.

Objective. Ionization chambers, mostly used for beam calibration and for reference dosimetry, can show high recombination effects in pulsed high dose rate proton beams. The aims of this paper are: first, to characterize the linearity response of newly designed asymmetrical beam monitor chambers (ABMC) in a 100-226 MeV pulsed high dose rate per pulse scanned proton beam; and secondly, to calibrate the ABMC with a PPC05 (IBA Dosimetry) plane parallel ionization chamber and compare to calibration with a home-made Faraday cup (FC).Approach. The ABMC response linearity was evaluated with both the FC and a PTW 60019 microDiamond detector. Regarding ionometry-based ABMC calibration, recombination factors were evaluated theoretically, then numerically, and finally experimentally measured in water for a plane parallel ionization chamber PPC05 (IBA Dosimetry) throughkssaturation curves. Finally, ABMC calibration was also achieved with FC and compared to the ionometry method for 7 energies.Main results. Linearity measurements showed that recombination losses in the new ABMC design were well taken into account for the whole range of the machine dose rates. The two-voltage-method was not suitable for recombination correction, but Jaffé's plots analysis was needed, emphasizing the current IAEA TRS-398 reference protocol limitations. Concerning ABMC calibration, FC based absorbed dose estimation and PPC05-based absorbed dose estimation differ by less than 6.3% for the investigated energies.Significance.So far, no update on reference dosimetry protocols is available to estimate the absorbed dose in ionization chambers for clinical high dose rate per pulse pulsed scanned proton beams. This work proposes a validation of the new ABMC design, a method to take into account the recombination effect for ionometry-based ABMC calibration and a comparison with FC dose estimation in this type of proton beams.

Range verification of a clinical proton beam in an abdominal phantom by co-registration of ionoacoustics and ultrasound.

Objective.The range uncertainty in proton radiotherapy is a limiting factor to achieve optimum dose conformity to the tumour volume. Ionoacoustics is a promising approach forin siturange verification, which would allow to reduce the size of the irradiated volume relative to the tumour volume. The energy deposition of a pulsed proton beam leads to an acoustic pressure wave (ionoacoustics), the detection of which allows conclusion about the distance between the Bragg peak and the acoustic detector. This information can be transferred into a co-registered ultrasound image, marking the Bragg peak position relative to the surrounding anatomy.Approach.A CIRS 3D abdominal phantom was irradiated with 126 MeV protons at a clinical proton therapy centre. Acoustic signals were recorded on the beam axis distal to the Bragg peak with a Cetacean C305X hydrophone. The ionoacoustic measurements were processed with a correlation filter using simulated filter templates. The hydrophone was rigidly attached to an ultrasound device (Interson GP-C01) recording ultrasound images of the irradiated region.Main results.The time of flight obtained from ionoacoustic measurements were transferred to an ultrasound image by means of an optoacoustic calibration measurement. The Bragg peak position was marked in the ultrasound image with a statistical uncertainty ofσ= 0.5 mm of 24 individual measurements depositing 1.2 Gy at the Bragg peak. The difference between the evaluated Bragg peak position and the one obtained from irradiation planning (1.0 mm) is smaller than the typical range uncertainty (≈4 mm) at the given penetration depth (10 cm).Significance.The measurements show that it is possible to determine the Bragg peak position of a clinical proton beam with submillimetre precision and transfer the information to an ultrasound image of the irradiated region. The dose required for this is smaller than that used for a typical irradiation fraction.

Proton beam range verification by means of ionoacoustic measurements at clinically relevant doses using a correlation-based evaluation.

Purpose: The Bragg peak located at the end of the ion beam range is one of the main advantages of ion beam therapy compared to X-Ray radiotherapy. However, verifying the exact position of the Bragg peak within the patient online is a major challenge. The goal of this work was to achieve submillimeter proton beam range verification for pulsed proton beams of an energy of up to 220 MeV using ionoacoustics for a clinically relevant dose deposition of typically 2 Gy per fraction by i) using optimal proton beam characteristics for ionoacoustic signal generation and ii) improved signal detection by correlating the signal with simulated filter templates. Methods: A water tank was irradiated with a preclinical 20 MeV proton beam using different pulse durations ranging from 50 ns up to 1 µs in order to maximise the signal-to-noise ratio (SNR) of ionoacoustic signals. The ionoacoustic signals were measured using a piezo-electric ultrasound transducer in the MHz frequency range. The signals were filtered using a cross correlation-based signal processing algorithm utilizing simulated templates, which enhances the SNR of the recorded signals. The range of the protons is evaluated by extracting the time of flight (ToF) of the ionoacoustic signals and compared to simulations from a Monte Carlo dose engine (FLUKA). Results: Optimised SNR of 28.0 ± 10.6 is obtained at a beam current of 4.5 µA and a pulse duration of 130 ns at a total peak dose deposition of 0.5 Gy. Evaluated ranges coincide with Monte Carlo simulations better than 0.1 mm at an absolute range of 4.21 mm. Higher beam energies require longer proton pulse durations for optimised signal generation. Using the correlation-based post-processing filter a SNR of 17.8 ± 5.5 is obtained for 220 MeV protons at a total peak dose deposition of 1.3 Gy. For this clinically relevant dose deposition and proton beam energy, submillimeter range verification was achieved at an absolute range of 303 mm in water. Conclusion: Optimal proton pulse durations ensure an ideal trade-off between maximising the ionoacoustic amplitude and minimising dose deposition. In combination with a correlation-based post-processing evaluation algorithm, a reasonable SNR can be achieved at low dose levels putting clinical applications for online proton or ion beam range verification into reach.

Satellite glia of the adult dorsal root ganglia harbor stem cells that yield glia under physiological conditions and neurons in response to injury.

The presence of putative stem/progenitor cells has been suggested in adult peripheral nervous system (PNS) tissue, including the dorsal root ganglion (DRG). To date, their identification and fate in pathophysiological conditions have not been addressed. Combining multiple in vitro and in vivo approaches, we identified the presence of stem cells in the adult DRG satellite glial population, and progenitors were present in the DRGs and sciatic nerve. Cell-specific transgenic mouse lines highlighted the proliferative potential of DRG stem cells and progenitors in vitro. DRG stem cells had gliogenic and neurogenic potentials, whereas progenitors were essentially gliogenic. Lineage tracing showed that, under physiological conditions, adult DRG stem cells maintained DRG homeostasis by supplying satellite glia. Under pathological conditions, adult DRG stem cells replaced DRG neurons lost to injury in addition of renewing the satellite glial pool. These novel findings open new avenues for development of therapeutic strategies targeting DRG stem cells for PNS disorders.

Fabrication and characterization of a multimodal 3D printed mouse phantom for ionoacoustic quality assurance in image-guided pre-clinical proton radiation research.

Objective.Image guidance and precise irradiation are fundamental to ensure the reliability of small animal oncology studies. Accurate positioning of the animal and the in-beam monitoring of the delivered radio-therapeutic treatment necessitate several imaging modalities. In the particular context of proton therapy with a pulsed beam, information on the delivered dose can be retrieved by monitoring the thermoacoustic waves resulting from the brief and local energy deposition induced by a proton beam (ionoacoustics). The objective of this work was to fabricate a multimodal phantom (x-ray, proton, ultrasound, and ionoacoustics) allowing for sufficient imaging contrast for all the modalities.Approach.The phantom anatomical parts were extracted from mouse computed tomography scans and printed using polylactic acid (organs) and a granite/polylactic acid composite (skeleton). The anatomical pieces were encapsulated in silicone rubber to ensure long term stability. The phantom was imaged using x-ray cone-beam computed tomography, proton radiography, ultrasound imaging, and monitoring of a 20 MeV pulsed proton beam using ionoacoustics.Main results.The anatomical parts could be visualized in all the imaging modalities validating the phantom capability to be used for multimodal imaging. Ultrasound images were simulated from the x-ray cone-beam computed tomography and co-registered with ultrasound images obtained before the phantom irradiation and low-resolution ultrasound images of the mouse phantom in the irradiation position, co-registered with ionoacoustic measurements. The latter confirmed the irradiation of a tumor surrogate for which the reconstructed range was found to be in reasonable agreement with the expectation.Significance.This study reports on a realistic small animal phantom which can be used to investigate ionoacoustic range (or dose) verification together with ultrasound, x-ray, and proton imaging. The co-registration between ionoacoustic reconstructions of the impinging proton beam and x-ray imaging is assessed for the first time in a pre-clinical scenario.

Covid-19 lockdown showed a likely beneficial effect on diabetic foot ulcers.

AIMS: During the Covid-19 epidemic, many countries imposed population lockdown. This study aimed to analyse diabetic foot ulcer (DFU) evolution of outpatients between the lockdown period and 1 month after its end. MATERIALS AND METHODS: We conducted a prospective, observational, single-centre study without modification of care. All patients who followed up for a DFU in the study centre between 15 April 2020 and 11 May 2020 were included. The baseline assessment occurred 4 weeks after the beginning of lockdown and the follow-up visit 4-6 weeks after easing of lockdown. The primary analysis was based on the Site, Ischaemia, Neuropathy, Bacterial infection, Area, Depth (SINBAD) classification. RESULTS: Twenty-seven patients were included, median 69.4 years, and 25 were followed-up at easing of lockdown. The median SINBAD score was 2 (interquartile range 1; 3) at inclusion and 1 (1; 2) at easing of lockdown, with a mean change of -0.32 (95% confidence interval -0.93; 0.29). Seventy-two percent of the population had a stable or improved score between the two visits. The proportion of patients using off-loading footwear was higher among those whose SINBAD score improved compared to those whose score worsened or remained stable (72%, 44% and 28%, respectively). Diabetes type was linked to DFU prognosis. Five patients (20%) were hospitalized during the follow-up period. CONCLUSION: Lockdown appears to have had a positive effect on DFU if patients remain under the care of their expert wound centre. We believe this effect is related to better compliance with offloading. The wide use of tele-medicine seems relevant for the follow-up of DFU.

XIORT-MC: A real-time MC-based dose computation tool for low- energy X-rays intraoperative radiation therapy.

PURPOSE: The INTRABEAM system is a miniature accelerator for low-energy X-ray Intra-Operative Radiation Therapy (IORT), and it could benefit from a fast and accurate dose computation tool. With regards to accuracy, dose computed with Monte Carlo (MC) simulations are the gold standard, however, they require a large computational effort and consequently they are not suitable for real-time dose planning. This work presents a comparison of the implementation on Graphics Processing Unit (GPU) of two different dose calculation algorithms based on MC phase-space (PHSP) information to compute dose distributions for the INTRABEAM device within seconds and with the accuracy of realistic MC simulations. METHODS: The MC-based algorithms we present incorporate photoelectric, Compton and Rayleigh effects for the interaction of low-energy X-rays. XIORT-MC (X-ray Intra-Operative Radiation Therapy Monte Carlo) includes two dose calculation algorithms; a Woodcock-based MC algorithm (WC-MC) and a Hybrid MC algorithm (HMC), and it is implemented in CPU and in GPU. Detailed MC simulations have been generated to validate our tool in homogeneous and heterogeneous conditions with all INTRABEAM applicators, including three clinically realistic CT-based simulations. A performance study has been done to determine the acceleration reached with the code, in both CPU and GPU implementations. RESULTS: Dose distributions were obtained with the HMC and the WC-MC and compared to standard reference MC simulations with more than 95% voxels fulfilling a 7%-0.5 mm gamma evaluation in all the cases considered. The CPU-HMC is 100 times more efficient than the reference MC, and the CPU-WC-MC is about 50 times more efficient. With the GPU implementation, the particle tracking of the WC-MC is faster than the HMC, with the extraction of the particle's information from the PHSP file taking a major part of the time. However, thanks to the variance reduction techniques implemented in the HMC, up to 400 times less particles are needed in the HMC to reach the same level of noise than the WC-MC. Therefore, in our implementation for INTRABEAM energies, the HMC is about 1.3 times more efficient than the WC-MC in an NVIDIA GeForce GTX 1080 Ti card and about 5.5 times more efficient in an NVIDIA GeForce RTX 3090. Dose with noise below 5% has been obtained in realistic situations in less than 5 s with the WC-MC and in less than 0.5 s with the HMC. CONCLUSIONS: The XIORT-MC is a dose computation tool designed to take full advantage of modern GPUs, making possible to obtain MC-grade accurate dose distributions within seconds. Its high speed allows a real-time dose calculation that includes the realistic effects of the beam in voxelized geometries of patients. It can be used as a dose-planning tool in the operating room during a XIORT treatment with any INTRABEAM device.

Correction of the measured current of a small-gap plane-parallel ionization chamber in proton beams in the presence of charge multiplication.

PURPOSE: The aims of this work are to study the response of a small-gap plane-parallel ionization chamber in the presence of charge multiplication and suggest an experimental method to determine the product of the recombination correction factor (ks) and the charge multiplication correction factor (kCM) in order to investigate the latter. METHODS: Experimental data were acquired in scanned proton beams and in a Cobalt-60 beam. Measurements were carried out using an IBA PPC05 chambers of which the electrode gap is 0.6mm. The study is based on the determination of Jaffé plots by operating the chambers at different voltages. Experimental results are compared to theoretical equations describing initial and volume recombination as well as charge multiplication for continuous and pulsed beams. RESULTS: Results obtained in protons and Cobalt-60 with the same PPC05 chamber indicate that the charge multiplication effect is independent of the beam quality, while results obtained in different proton beams with two different PPC05 chambers show that the charge multiplication effect is chamber dependent. CONCLUSIONS: The approach to be taken when using a small-gap plane-parallel ionization chamber with a high voltage (e.g. 300V or 500V) for reference dosimetry in scanned proton beams depends on which correction factors were applied to the chamber response during its calibration in terms of absorbed dose to water: In both cases, it is recommended to use the ionization chamber at the same operating voltage used during its ND,w-calibration. Another solution consists of operating the PPC05 chamber at a lower voltage (e.g. 50V) with larger ks and smaller kCM and determining the product of both factors with higher accuracy using a linear extrapolation method.

Computer-assisted beam modeling for particle therapy.

PURPOSE: To develop a computer-driven and thus less user-dependent method, allowing for a simple and straightforward generation of a Monte Carlo (MC) beam model of a scanned proton and carbon ion beam delivery system. METHODS: In a first step, experimental measurements were performed for proton and carbon ion energies in the available energy ranges. Data included depth dose profiles measured in water and spot sizes in air at various isocenter distances. Using an automated regularization-based optimization process (AUTO-BEAM), GATE/Geant4 beam models of the respective beam lines were generated. These were obtained sequentially by using least square weighting functions with and without regularization, to iteratively tune the beam parameters energy, energy spread, beam sigma, divergence, and emittance until a user-defined agreement was reached. Based on the parameter tuning for a set of energies, a beam model was semi-automatically generated. The resulting beam models were validated for all centers comparing to independent measurements of laterally integrated depth dose curves and spot sizes in air. For one representative center, three-dimensional dose cubes were measured and compared to simulations. The method was applied on one research as well as four different clinical beam lines for proton and carbon ions of three different particle therapy centers using synchrotron or cyclotron accelerator systems: (a) MedAustron ion therapy center, (b) University Proton Therapy Dresden, and (c) Center Antoine Lacassagne Nice. RESULTS: Particle beam ranges in the MC beam models agreed on average within 0.2 mm compared to measurements for all energies and beam lines. Spot sizes in air (full-width at half maximum) at all positions differed by less than 0.4% from the measurements. Dose calculation with the beam model for the clinical beam line at MedAustron agreed better than 1.7% in absolute dose for a representative clinical case treated with protons. For protons, beam model generation, including geometry creation, data conversion, and validation, was possible within three working days. The number of iterations required for the optimization process to converge, was found to be similar for all beam line geometries and particle types. CONCLUSION: The presented method was demonstrated to work independently of the beam optics behavior of the different beam lines, particle types, and geometries. Furthermore, it is suitable for non-expert users and requires only limited user interaction. Beam model validation for different beam lines based on different beam delivery systems, showed good agreement.

Myelination of parvalbumin interneurons shapes the function of cortical sensory inhibitory circuits.

Myelination of projection neurons by oligodendrocytes is key to optimize action potential conduction over long distances. However, a large fraction of myelin enwraps the axons of parvalbumin-positive fast-spiking interneurons (FSI), exclusively involved in local cortical circuits. Whether FSI myelination contributes to the fine-tuning of intracortical networks is unknown. Here we demonstrate that FSI myelination is required for the establishment and maintenance of the powerful FSI-mediated feedforward inhibition of cortical sensory circuits. The disruption of GABAergic synaptic signaling of oligodendrocyte precursor cells prior to myelination onset resulted in severe FSI myelination defects characterized by longer internodes and nodes, aberrant myelination of branch points and proximal axon malformation. Consequently, high-frequency FSI discharges as well as FSI-dependent postsynaptic latencies and strengths of excitatory neurons were reduced. These dysfunctions generated a strong excitation-inhibition imbalance that correlated with whisker-dependent texture discrimination impairments. FSI myelination is therefore critical for the function of mature cortical inhibitory circuits.

Evaluation of GATE-RTion (GATE/Geant4) Monte Carlo simulation settings for proton pencil beam scanning quality assurance.

PURPOSE: Geant4 is a multi-purpose Monte Carlo simulation tool for modeling particle transport in matter. It provides a wide range of settings, which the user may optimize for their specific application. This study investigates GATE/Geant4 parameter settings for proton pencil beam scanning therapy. METHODS: GATE8.1/Geant4.10.3.p03 (matching the versions used in GATE-RTion1.0) simulations were performed with a set of prebuilt Geant4 physics lists (QGSP_BIC, QGSP_BIC_EMY, QGSP_BIC_EMZ, QGSP_BIC_HP_EMZ), using 0.1mm-10mm as production cuts on secondary particles (electrons, photons, positrons) and varying the maximum step size of protons (0.1mm, 1mm, none). The results of the simulations were compared to measurement data taken during clinical patient specific quality assurance at The Christie NHS Foundation Trust pencil beam scanning proton therapy facility. Additionally, the influence of simulation settings was quantified in a realistic patient anatomy based on computer tomography (CT) scans. RESULTS: When comparing the different physics lists, only the results (ranges in water) obtained with QGSP_BIC (G4EMStandardPhysics_Option0) depend on the maximum step size. There is clinically negligible difference in the target region when using High Precision neutron models (HP) for dose calculations. The EMZ electromagnetic constructor provides a closer agreement (within 0.35 mm) to measured beam sizes in air, but yields up to 20% longer execution times compared to the EMY electromagnetic constructor (maximum beam size difference 0.79 mm). The impact of this on patient-specific quality assurance simulations is clinically negligible, with a 97% average 2%/2 mm gamma pass rate for both physics lists. However, when considering the CT-based patient model, dose deviations up to 2.4% are observed. Production cuts do not substantially influence dosimetric results in solid water, but lead to dose differences of up to 4.1% in the patient CT. Small (compared to voxel size) production cuts increase execution times by factors of 5 (solid water) and 2 (patient CT). CONCLUSIONS: Taking both efficiency and dose accuracy into account and considering voxel sizes with 2 mm linear size, the authors recommend the following Geant4 settings to simulate patient specific quality assurance measurements: No step limiter on proton tracks; production cuts of 1 mm for electrons, photons and positrons (in the phantom and range-shifter) and 10 mm (world); best agreement to measurement data was found for QGSP_BIC_EMZ reference physics list at the cost of 20% increased execution times compared to QGSP_BIC_EMY. For simulations considering the patient CT model, the following settings are recommended: No step limiter on proton tracks; production cuts of 1 mm for electrons, photons and positrons (phantom/range-shifter) and 10 mm (world) if the goal is to achieve sufficient dosimetric accuracy to ensure that a plan is clinically safe; or 0.1 mm (phantom/range-shifter) and 1 mm (world) if higher dosimetric accuracy is needed (increasing execution times by a factor of 2); most accurate results expected for QGSP_BIC_EMZ reference physics list, at the cost of 10-20% increased execution times compared to QGSP_BIC_EMY.

LifeTime and improving European healthcare through cell-based interceptive medicine.

Here we describe the LifeTime Initiative, which aims to track, understand and target human cells during the onset and progression of complex diseases, and to analyse their response to therapy at single-cell resolution. This mission will be implemented through the development, integration and application of single-cell multi-omics and imaging, artificial intelligence and patient-derived experimental disease models during the progression from health to disease. The analysis of large molecular and clinical datasets will identify molecular mechanisms, create predictive computational models of disease progression, and reveal new drug targets and therapies. The timely detection and interception of disease embedded in an ethical and patient-centred vision will be achieved through interactions across academia, hospitals, patient associations, health data management systems and industry. The application of this strategy to key medical challenges in cancer, neurological and neuropsychiatric disorders, and infectious, chronic inflammatory and cardiovascular diseases at the single-cell level will usher in cell-based interceptive medicine in Europe over the next decade.

Information about action outcomes differentially affects learning from self-determined versus imposed choices.

The valence of new information influences learning rates in humans: good news tends to receive more weight than bad news. We investigated this learning bias in four experiments, by systematically manipulating the source of required action (free versus forced choices), outcome contingencies (low versus high reward) and motor requirements (go versus no-go choices). Analysis of model-estimated learning rates showed that the confirmation bias in learning rates was specific to free choices, but was independent of outcome contingencies. The bias was also unaffected by the motor requirements, thus suggesting that it operates in the representational space of decisions, rather than motoric actions. Finally, model simulations revealed that learning rates estimated from the choice-confirmation model had the effect of maximizing performance across low- and high-reward environments. We therefore suggest that choice-confirmation bias may be adaptive for efficient learning of action-outcome contingencies, above and beyond fostering person-level dispositions such as self-esteem.

Proton therapy for head and neck squamous cell carcinomas: A review of the physical and clinical challenges.

The quality of radiation therapy has been shown to significantly influence the outcomes for head and neck squamous cell carcinoma (HNSCC) patients. The results of dosimetric studies suggest that intensity-modulated proton therapy (IMPT) could be of added value for HNSCC by being more effective than intensity-modulated (photon) radiation therapy (IMRT) for reducing side effects of radiation therapy. However, the physical properties of protons make IMPT more sensitive than photons to planning uncertainties. This could potentially have a negative effect on the quality of IMPT planning and delivery. For this review, the three French proton therapy centers collaborated to evaluate the differences between IMRT and IMPT. The review explored the effects of these uncertainties and their management for developing a robust and optimized IMPT treatment delivery plan to achieve clinical outcomes that are superior to those for IMRT. We also provide practical suggestions for the management of HNSCC carcinoma with IMPT. Because metallic dental implants can increase range uncertainties (3-10%), patient preparation for IMPT may require more systematic removal of in-field alien material than is done for IMRT. Multi-energy CT may be an alternative to calculate more accurately the dose distribution. The practical aspects that we describe are essential to guarantee optimal quality in radiation therapy in both model-based and randomized clinical trials.

Early Toxicities After High Dose Rate Proton Therapy in Cancer Treatments.

BACKGROUND: The conventional dose rate of radiation therapy is 0.01-0.05 Gy per second. According to preclinical studies, an increased dose rate may offer similar anti-tumoral effect while dramatically improving normal tissue protection. This study aims at evaluating the early toxicities for patients irradiated with high dose rate pulsed proton therapy (PT). MATERIALS AND METHODS: A single institution retrospective chart review was performed for patients treated with high dose rate (10 Gy per second) pulsed proton therapy, from September 2016 to April 2020. This included both benign and malignant tumors with ≥3 months follow-up, evaluated for acute (≤2 months) and subacute (>2 months) toxicity after the completion of PT. RESULTS: There were 127 patients identified, with a median follow up of 14.8 months (3-42.9 months). The median age was 55 years (1.6-89). The cohort most commonly consisted of benign disease (55.1%), cranial targets (95.1%), and were treated with surgery prior to PT (56.7%). There was a median total PT dose of 56 Gy (30-74 Gy), dose per fraction of 2 Gy (1-3 Gy), and CTV size of 47.6 ml (5.6-2,106.1 ml). Maximum acute grade ≥2 toxicity were observed in 49 (38.6%) patients, of which 8 (6.3%) experienced grade 3 toxicity. No acute grade 4 or 5 toxicity was observed. Maximum subacute grade 2, 3, and 4 toxicity were discovered in 25 (19.7%), 12 (9.4%), and 1 (0.8%) patient(s), respectively. CONCLUSION: In this cohort, utilizing high dose rate proton therapy (10 Gy per second) did not result in a major decrease in acute and subacute toxicity. Longer follow-up and comparative studies with conventional dose rate are required to evaluate whether this approach offers a toxicity benefit.

The cerebral cortex is a substrate of multiple interactions between GABAergic interneurons and oligodendrocyte lineage cells.

In the cerebral cortex, GABAergic interneurons and oligodendrocyte lineage cells share different characteristics and interact despite being neurons and glial cells, respectively. These two distinct cell types share common embryonic origins and are born from precursors expressing similar transcription factors. Moreover, they highly interact with each other through different communication mechanisms during development. Notably, cortical oligodendrocyte precursor cells (OPCs) receive a major and transient GABAergic synaptic input, preferentially from parvalbumin-expressing interneurons, a specific interneuron subtype recently recognized as highly myelinated. In this review, we highlight the similarities and interactions between GABAergic interneurons and oligodendrocyte lineage cells in the cerebral cortex and suggest potential roles of this intimate interneuron-oligodendroglia relationship in cortical construction. We also propose new lines of research to understand the role of the close link between interneurons and oligodendroglia during cortical development and in pathological conditions such as schizophrenia.