Low-dose ionizing γ-radiation elicits the extrusion of neutrophil extracellular traps.

PURPOSE: Cancer patients frequently undergo radiotherapy in their clinical management with unintended irradiation of blood vessels and copiously irrigated organs in which polymorphonuclear leukocytes circulate. Following the observation that such low doses of ionizing radiation are able to induce neutrophils to extrude neutrophil extracellular traps (NETs), we have investigated the mechanisms, consequences and the occurrence of such phenomena in patients undergoing radiotherapy. EXPERIMENTAL DESIGN: NETosis was analyzed in cultures of neutrophils isolated from healthy donors, cancer patients and cancer-bearing mice under confocal microscopy. Cocultures of radiation-induced NETs, immune effector lymphocytes and tumor cells were used to study the effects of irradiation-induced NETs on immune cytotoxicity. Radiation-induced NETs were intravenously injected to mice assessing their effects on metastasis. Circulating NETs in irradiated cancer patients were measured by ELISA methods detecting MPO-DNA complexes and citrullinated H3. RESULTS: Very low γ-radiation doses (0.5-1 Gy) given to neutrophils elicit NET formation in a manner dependent on oxidative stress, NADPH oxidase activity and autocrine interleukin-8. Radiation-induced NETs interfere with NK- and T-cell cytotoxicity. As a consequence, pre-injection of irradiation-induced NETs increases the number of successful metastases in mouse tumor models. Increases in circulating NETs were readily detected in two prospective series of patients following the first fraction of their radiotherapy courses. CONCLUSIONS: NETosis is induced by low-dose ionizing irradiation in a neutrophil-intrinsic fashion and radiation-induced NETs are able to interfere with immune-mediated cytotoxicity. Radiation-induced NETs foster metastasis in mouse models and can be detected in the circulation of patients undergoing conventional radiotherapy treatments.

Detailed dosimetric evaluation of inter-fraction and respiratory motion in lung stereotactic body radiation therapy based on daily 4D cone beam CT images.

Objective. Periodic respiratory motion and inter-fraction variations are sources of geometric uncertainty in stereotactic body radiation therapy (SBRT) of pulmonary lesions. This study extensively evaluates and validates the separate and combined dosimetric effect of both factors using 4D-CT and daily 4D-cone beam CT (CBCT) dose accumulation scenarios.Approach. A first cohort of twenty early stage or metastatic disease lung cancer patients were retrospectively selected to evaluate each scenario. The planned-dose (3DRef) was optimized on a 3D mid-position CT. To estimate the dosimetric impact of respiratory motion (4DRef), inter-fractional variations (3DAcc) and the combined effect of both factors (4DAcc), three dose accumulation scenarios based on 4D-CT, daily mid-cone beam CT (CBCT) position and 4D-CBCT were implemented via CT-CT/CT-CBCT deformable image registration (DIR) techniques. Each scenario was compared to 3DRef.A separate cohort of ten lung SBRT patients was selected to validate DIR techniques. The distance discordance metric (DDM) was implemented per voxel and per patient for tumor and organs at risk (OARs), and the dosimetric impact for CT-CBCT DIR geometric errors was calculated.Main results.Median and interquartile range (IQR) of the dose difference per voxel were 0.05/2.69 Gy and -0.12/2.68 Gy for3DAcc-3DRefand4DAcc-3DRef.For4DRef-3DRefthe IQR was considerably smaller -0.15/0.78 Gy. These findings were confirmed by dose volume histogram parameters calculated in tumor and OARs. For CT-CT/CT-CBCT DIR validation, DDM (95th percentile) was highest for heart (6.26 mm)/spinal cord (8.00 mm), and below 3 mm for tumor and the rest of OARs. The dosimetric impact of CT-CBCT DIR errors was below 2 Gy for tumor and OARs.Significance. The dosimetric impact of inter-fraction variations were shown to dominate those of periodic respiration in SBRT for pulmonary lesions. Therefore, treatment evaluation and dose-effect studies would benefit more from dose accumulation focusing on day-to-day changes then those that focus on respiratory motion.

Simple and Autonomous Sleep Signal Processing System for the Detection of Obstructive Sleep Apneas.

Obstructive sleep apnea (OSA) is a common sleep disorder characterized by repetitive upper airway obstruction, intermittent hypoxemia, and recurrent awakenings during sleep. The most used treatment for this syndrome is a device that generates a positive airway pressure­Continuous Positive Airway Pressure (CPAP), but it works continuously, whether or not there is apnea. An alternative consists on systems that detect apnea episodes and produce a stimulus that eliminates them. Article focuses on the development of a simple and autonomous processing system for the detection of obstructive sleep apneas, using polysomnography (PSG) signals: electroencephalography (EEG), electromyography (EMG), respiratory effort (RE), respiratory flow (RF), and oxygen saturation (SO2). The system is evaluated using, as a gold standard, 20 PSG tests labeled by sleep experts and it performs two analyses. A first analysis detects awake/sleep stages and is based on the accumulated amplitude in a channel-dependent frequency range, according to the criteria of the American Academy of Sleep Medicine (AASM). The second analysis detects hypopneas and apneas, based on analysis of the breathing cycle and oxygen saturation. The results show a good estimation of sleep events, where for 75% of the cases of patients analyzed it is possible to determine the awake/asleep states with an effectiveness of >92% and apneas and hypopneas with an effectiveness of >55%, through a simple processing system that could be implemented in an electronic device to be used in possible OSA treatments.

Evaluation of the Ultrastructural and In Vitro Flow Properties of the PRESERFLO MicroShunt.

Purpose: To measure the in vitro flow properties of the PRESERFLO implant for comparison with the theoretical resistance to flow. Methods: The PRESERFLO was designed to control the flow of aqueous humor according to the Hagen-Poiseuille (HP) equation. Scanning electron microscopy (SEM) was performed to analyze the ultrastructure, and flow measurements were carried out using a gravity-flow setup. Results: SEM images of the PRESERFLO showed luminal diameters of 67.73 × 65.95 µm and 63.66 × 70.54 µm. The total diameter was 337.2 µm, and the wall was 154 µm wide. The theoretical calculation of the resistance to flow (R) for an aqueous humor (AH) viscosity of 0.7185 centipoises (cP) was 1.3 mm Hg/(µL/min). Hence, assuming a constant AH flow of 2 µL/min, the pressure differential across the device (ΔP) was estimated to be 2.6 mm Hg. The gravity-flow experiment allowed us to measure the experimental resistance to flow, which was RE = 1.301 mm Hg/(µL/min), in agreement with the theoretical resistance to flow R given by the HP equation. Conclusions: The experimental and theoretical flow testing showed that the pressure drop across this device would not be large enough to avoid hypotony unless the resistance to outflow of the sub-Tenon space was sufficient to control the intraocular pressure in the early postoperative period. Translational Relevance: The fluid properties of glaucoma subconjunctival drainage devices determine their specific bleb-forming capacity and ability to avoid hypotony and therefore their safety and efficacy profile.

A method using 4D dose accumulation to quantify the interplay effect in lung stereotactic body radiation therapy.

The purpose of this study was to devise and evaluate a method to quantify the dosimetric uncertainty produced by the interplay between the movement of multileaf collimator and respiratory motion in lung stereotactic body radiation therapy. The method calculates the dose distribution for all control points from a dynamic treatment in all respiratory phases. The methodology includes some characteristics of a patient's irregular breathing patterns. It selects, for each control point, the phases with maximum and minimum mean dose over the tumor and their corresponding adjacent phases, whenever necessary. According to this selection, the dose matrices from each control point are summed up to obtain two dose distributions in each phase, which are accumulated in the reference phase subsequently by deformable image registration (DIR). D 95 and [Formula: see text] were calculated over those accumulated dose distributions for Gross Tumor Volume (GTV), Planning Target Volume-based on Internal Target Volume approach-and Evaluation Target Volume (ETV), a novel concept that applies to 4D dose accumulation. With the ETV, DIR and interplay uncertainties are separated. The methodology also evaluated how variations in the breathing rate and field size affects the mean dose received by the GTV. The method was applied retrospectively in five patients treated with intensity modulated radiotherapy-minimum area defined by the leaves configuration at any control point was at least 4 cm2. Uncertainties in tumor coverage were small (in most patients, changes on D 95 and [Formula: see text] were below 2% for GTV and ETV) but significant over- and under-dosages near ETV, which can be accentuated by highly irregular breathing. Uncertainties in mean dose for GTV tended to decrease exponentially with increasing field size and were reduced by an increase of breathing rate. The implementation of this method would be helpful to assess treatment quality in patients with irregular breathing. Furthermore, it could be used to study interplay uncertainties when small field sizes are used.

A novel concept to include uncertainties in the evaluation of stereotactic body radiation therapy after 4D dose accumulation using deformable image registration.

PURPOSE: To use four-dimensional (4D) dose accumulation based on deformable image registration (DIR) to assess dosimetric uncertainty in lung stereotactic body radiation therapy (SBRT) treatment planning. A novel concept, the Evaluation Target Volume (ETV), was introduced to achieve this goal. METHODS: The internal target volume (ITV) approach was used for treatment planning for 11 patients receiving lung SBRT. Retrospectively, 4D dose calculation was done in Pinnacle v9.10. Total dose was accumulated in the reference phase using DIR with MIM. DIR was validated using landmarks introduced by an expert radiation oncologist. The 4D and three-dimensional (3D) dose distributions were compared within the gross tumor volume (GTV) and the planning target volume (PTV) using the D95 and Dmin (calculated as Dmin,0.035cc ) metrics. For lung involvement, the mean dose and V20 , V10 , and V5 were used in the 3D to 4D dose comparison, and Dmax (D0.1cc ) was used for all other organs at risk (OAR). The new evaluation target volume (ETV) was calculated by expanding the GTV in the reference phase in order to include geometrical uncertainties of the DIR, interobserver variability in the definition of the tumor, and uncertainties of imaging and delivery systems. D95 and Dmin,0.035cc metrics were then calculated on the basis of the ETV for 4D accumulated dose distributions, and these metrics were compared with those calculated from the PTV for 3D planned dose distributions. RESULTS: The target registration error (TRE) per spatial component was below 0.5 ± 2.1mm for all our patients. For five patients, dose degradation above 2% (>4% in 2 patients) was found in the PTV after 4D accumulation and attributed to anatomical variations due to breathing. Comparison of D95 and Dmin,0.035cc metrics showed that the ETV (4D accumulated dose) estimated substantially lower coverage than the PTV (3D planning dose): in six out of the 11 cases, and for at least for one of the two metrics, coverage estimated by ETV was at least 5% lower than that estimated by PTV. Furthermore, the ETV approach revealed hot and cold spots within its boundaries. CONCLUSIONS: A workflow for 4D dose accumulation based on DIR has been devised. Dose degradation was attributed to respiratory motion. To overcome limitations in the PTV for the purposes of evaluating DIR-based 4D accumulated dose distributions, a new concept, the ETV, was proposed. This concept appears to facilitate more reliable dose evaluation and a better understanding of dosimetric uncertainties due to motion and deformation.

Accuracy of a Laryngopharyngeal Endoscopic Esthesiometer (LPEER) for Evaluating Laryngopharyngeal Mechanosensitivity: A Validation Study in a Prospectively Recruited Cohort of Patients.

Recent studies have shown an association between alterations in laryngopharyngeal mechanosensitivity (LPMS) and dysphagia, obstructive sleep apnea, and chronic cough hypersensitivity syndrome. A previous reliability study of a new laryngopharyngeal endoscopic esthesiometer and rangefinder (LPEER) showed high intra- and inter-rater reliability; however, its accuracy has not been tested. We performed an accuracy study of the LPEER in a prospectively and consecutively recruited cohort of 118 patients at two tertiary care university hospitals. Most of the patients were suffering from dysphagia, and all of them underwent a standard clinical evaluation and fiberoptic endoscopic evaluation of swallowing with sensory testing (FEESST) using a new sensory testing protocol. The sensory test included determinations of the laryngeal adductor reflex threshold (LART), the cough reflex threshold (CRT) and the gag reflex threshold (GRT). Abnormalities on these reflex thresholds were evaluated for associations with major alterations in swallowing safety (pharyngeal residues, penetration, and aspiration). We evaluated the discriminative capacity of the LPMS test using ROC curves and the area under the curve (AUC-ROC) and its relationship with the eight-point penetration-aspiration scale (PAS) using the Spearman's ρ correlation coefficient (SCC). We found a positive correlation between the PAS and LART (SCC 0.47; P < 0.001), CRT (SCC 0.46; P < 0.001) and GRT (SCC 0.34; P = 0.002). The AUC-ROC values for detecting a PAS ≥7 were as follows: LART, 0.83 (P < 0.0001); CRT, 0.79 (P < 0.0001); GRT, 0.72 (P < 0.0001). In this study, the LPEER showed good accuracy for evaluating LPMS. These results justify further validation studies in independent populations.

Commissioning of small field size radiosurgery cones in a 6-MV flattening filter-free beam.

This study aimed to describe the commissioning of small field size radiosurgery cones in a 6-MV flattening filter free (FFF) beam and report our measured values. Four radiosurgery cones of diameters 5, 10, 12.5, and 15 mm supplied by Elekta Medical were commissioned in a 6-MV FFF beam from an Elekta Versa linear accelerator. The extraction of a reference signal for measuring small fields in scanning mode is challenging. A transmission chamber was attached to the lower part of the collimators and used for percentage depth dose (PDD) and profile measurements in scanning mode with a stereotactic diode. Tissue-maximum ratios (TMR) and output factors (OF) for all collimators were measured with a stereotactic diode (IBA). TMR and the OF for the largest collimator were also acquired on a polystyrene phantom with a microionization chamber of 0.016 cm3 volume (PTW Freiburg PinPoint 3D). Measured TMR with diode and PinPoint microionization chamber agreed very well with differences smaller than 1% for depths below 20 cm, except for the smaller collimator, for which differences were always smaller than 2%. Calculated TMR were significantly different (up to 7%) from measured TMR. OF measured with diode and chamber showed a difference of 3.5%. The use of a transmission chamber allowed the measurement of the small-field dosimetric properties with a simple setup. The commissioning of radiosurgery cones in FFF beams has been performed with essentially the same procedures and recommended detectors used with flattened beams. Good agreement was found between TMR measurements acquired with the IBA stereotactic diode and the PinPoint 3D microionization chamber. The transmission chamber overcomes the problem of extracting a reference signal and is of great help for small-field commissioning.

Reliability of a laryngo-pharyngeal esthesiometer and a method for measuring laryngo-pharyngeal mechano-sensitivity in a prospectively recruited cohort of patients.

BACKGROUND: There are not reliable methods for measuring laryngo-pharyngeal mechano-sensitivity (LPMS). We aimed to determine the reliability of a new method for measuring LPMS using a new laryngo-pharyngeal esthesiometer (LPEER) in a prospective cohort of dysphagic stroke and non-dysphagic patients. The patients underwent clinical and endoscopic evaluations of swallowing (FESSST). The LPMS assessments consisted of measurements by an expert and a novel rater of the laryngeal-adductor reflex threshold (LART), cough reflex threshold (CRT) and gag reflex threshold (GRT) using the LPEER. We assessed the Bland-Altman limits of agreement, the intraclass correlation coefficients (ICCs) and Spearman correlation coefficients (SCCs). For the inter-rater comparisons, we contrasted the expert and novel raters. A total of 1608 measurements were obtained from 34 dysphagic stroke patients and 33 non-dysphagic patients. The intra-rater ICCs for all reflex thresholds were >0.90. The inter-rater ICCs were 0.87 for the LART, 0.79 for the CRT and 0.70 for the GRT. The intra-rater SCCs for all reflex thresholds were above 0.88 (P < 0.0001). The inter-rater SCC were 0.80 for the LART, 0.79 for the CRT and 0.70 for the GRT (all P < 0.0001). The Bland-Altman plots revealed good agreement for the LART and CRT and moderate agreement for the GRT. The median normal value was 0.14 mN for the LART, 4.4 mN for the CRT and 11.9 mN for the GRT. The median thresholds values in patients with aspiration were LART: 1.31 mN; CRT: 32.9 mN and GRT: 32.9 mN (all P < 0.006 vs normal thresholds). The LPEER exhibited substantial to excellent intra- and inter-rater reliability.

Bifurcation induced by the aspect ratio in a turbulent von Kármán swirling flow.

We evaluate the effect of the aspect ratio, i.e., the distance between the propellers H divided by the diameter D, on the slow dynamics of a von Kármán swirling flow driven by two propellers in a closed cylinder. We use a cell with a fixed diameter D but where the distance between the propellers can be turned continuously and where the inertia from the propellers can also be changed using different gears. No change on the dynamics is observed when the momentum of inertia is modified. Some dramatic changes of the shear layer position are observed modifying the aspect ratio Γ=H/D. A bifurcation of the shear layer position appears. Whereas for low Γ the shear layer position has a smooth evolution when turning the asymmetry between the rotation frequency of the propellers, for high Γ the transition becomes abrupt and a symmetry breaking appears. Secondly we observe that the spontaneous reversals with large residence times already observed in this experiment for Γ=1 [de la Torre and Burguete, Phys. Rev. Lett. 99, 054101 (2007)PRLTAO0031-900710.1103/PhysRevLett.99.054101] exist only in a narrow window of aspect ratio. We show using an experimental study of the mean flow structure and a numerical approach based on a Langevin equation with colored noise that the shear layer position seems to be decided by the mean flow structure, whereas the reversals are linked to the spatial distribution of the turbulent fluctuations in the cell.

Design, development and validation of a new laryngo-pharyngeal endoscopic esthesiometer and range-finder based on the assessment of air-pulse variability determinants.

BACKGROUND: Laryngo-pharyngeal mechano-sensitivity (LPMS) is involved in dysphagia, sleep apnea, stroke, irritable larynx syndrome and cough hypersensitivity syndrome among other disorders. These conditions are associated with a wide range of airway reflex abnormalities. However, the current device for exploring LPMS is limited because it assesses only the laryngeal adductor reflex during fiber-optic endoscopic evaluations of swallowing and requires a high degree of expertise to obtain reliable results, introducing intrinsic expert variability and subjectivity. METHODS: We designed, developed and validated a new air-pulse laryngo-pharyngeal endoscopic esthesiometer with a built-in laser range-finder (LPEER) based on the evaluation and control of air-pulse variability determinants and on intrinsic observer variability and subjectivity determinants of the distance, angle and site of stimulus impact. The LPEER was designed to be capable of delivering precise and accurate stimuli with a wide range of intensities that can explore most laryngo-pharyngeal reflexes. RESULTS: We initially explored the potential factors affecting the reliability of LPMS tests and included these factors in a multiple linear regression model. The following factors significantly affected the precision and accuracy of the test (P < 0.001): the tube conducting the air-pulses, the supply pressure of the system, the duration of the air-pulses, and the distance and angle between the end of the tube conducting the air-pulses and the site of impact. To control all of these factors, an LPEER consisting of an air-pulse generator and an endoscopic laser range-finder was designed and manufactured. We assessed the precision and accuracy of the LPEER's stimulus and range-finder according to the coefficient of variation (CV) and by looking at the differences between the measured properties and the desired values, and we performed a pilot validation on ten human subjects. The air-pulses and range-finder exhibited good precision and accuracy (CV < 0.06), with differences between the desired and measured properties at <3 % and a range-finder measurement error of <1 mm. The tests in patients demonstrated obtainable and reproducible thresholds for the laryngeal adductor, cough and gag reflexes. CONCLUSIONS: The new LPEER was capable of delivering precise and accurate stimuli for exploring laryngo-pharyngeal reflexes.

Experimental pencil beam kernels derivation for 3D dose calculation in flattening filter free modulated fields.

This paper presents a method to obtain the pencil-beam kernels that characterize a megavoltage photon beam generated in a flattening filter free (FFF) linear accelerator (linac) by deconvolution from experimental measurements at different depths. The formalism is applied to perform independent dose calculations in modulated fields. In our previous work a formalism was developed for ideal flat fluences exiting the linac's head. That framework could not deal with spatially varying energy fluences, so any deviation from the ideal flat fluence was treated as a perturbation. The present work addresses the necessity of implementing an exact analysis where any spatially varying fluence can be used such as those encountered in FFF beams. A major improvement introduced here is to handle the actual fluence in the deconvolution procedure. We studied the uncertainties associated to the kernel derivation with this method. Several Kodak EDR2 radiographic films were irradiated with a 10 MV FFF photon beam from two linacs from different vendors, at the depths of 5, 10, 15, and 20cm in polystyrene (RW3 water-equivalent phantom, PTW Freiburg, Germany). The irradiation field was a 50mm diameter circular field, collimated with a lead block. The 3D kernel for a FFF beam was obtained by deconvolution using the Hankel transform. A correction on the low dose part of the kernel was performed to reproduce accurately the experimental output factors. Error uncertainty in the kernel derivation procedure was estimated to be within 0.2%. Eighteen modulated fields used clinically in different treatment localizations were irradiated at four measurement depths (total of fifty-four film measurements). Comparison through the gamma-index to their corresponding calculated absolute dose distributions showed a number of passing points (3%, 3mm) mostly above 99%. This new procedure is more reliable and robust than the previous one. Its ability to perform accurate independent dose calculations was demonstrated.

Development and clinical evaluation of a simple optical method to detect and measure patient external motion.

A simple and independent system to detect and measure the position of a number of points in space was devised and implemented. Its application aimed to detect patient motion during radiotherapy treatments, alert of out-of-tolerances motion, and record the trajectories for subsequent studies. The system obtains the 3D position of points in space, through its projections in 2D images recorded by two cameras. It tracks black dots on a white sticker placed on the surface of the moving object. The system was tested with linear displacements of a phantom, circular trajectories of a rotating disk, oscillations of an in-house phantom, and oscillations of a 4D phantom. It was also used to track 461 trajectories of points on the surface of patients during their radiotherapy treatments. Trajectories of several points were reproduced with accuracy better than 0.3 mm in the three spatial directions. The system was able to follow periodic motion with amplitudes lower than 0.5 mm, to follow trajectories of rotating points at speeds up to 11.5 cm/s, and to track accurately the motion of a respiratory phantom. The technique has been used to track the motion of patients during radiotherapy and to analyze that motion. The method is flexible. Its installation and calibration are simple and quick. It is easy to use and can be implemented at a very affordable price. Data collection does not involve any discomfort to the patient and does not delay the treatment, so the system can be used routinely in all treatments. It has an accuracy similar to that of other, more sophisticated, commercially available systems. It is suitable to implement a gating system or any other application requiring motion detection, such as 4D CT, MRI or PET.

Application of spherical diodes for megavoltage photon beams dosimetry.

PURPOSE: External beam radiation therapy (EBRT) usually uses heterogeneous dose distributions in a given volume. Designing detectors for quality control of these treatments is still a developing subject. The size of the detectors should be small to enhance spatial resolution and ensure low perturbation of the beam. A high uniformity in angular response is also a very important feature in a detector, because it has to measure radiation coming from all the directions of the space. It is also convenient that detectors are inexpensive and robust, especially to perform in vivo measurements. The purpose of this work is to introduce a new detector for measuring megavoltage photon beams and to assess its performance to measure relative dose in EBRT. METHODS: The detector studied in this work was designed as a spherical photodiode (1.8 mm in diameter). The change in response of the spherical diodes is measured regarding the angle of incidence, cumulated irradiation, and instantaneous dose rate (or dose per pulse). Additionally, total scatter factors for large and small fields (between 1 × 1 cm(2) and 20 × 20 cm(2)) are evaluated and compared with the results obtained from some commercially available ionization chambers and planar diodes. Additionally, the over-response to low energy scattered photons in large fields is investigated using a shielding layer. RESULTS: The spherical diode studied in this work produces a high signal (150 nC/Gy for photons of nominal energy of 15 MV and 160 for 6 MV, after 12 kGy) and its angular dependence is lower than that of planar diodes: less than 5% between maximum and minimum in all directions, and 2% around one of the axis. It also has a moderated variation with accumulated dose (about 1.5%/kGy for 15 MV photons and 0.7%/kGy for 6 MV, after 12 kGy) and a low variation with dose per pulse (± 0.4%), and its behavior is similar to commercial diodes in total scatter factor measurements. CONCLUSIONS: The measurements of relative dose using the spherical diode described in this work show its feasibility for the dosimetry of megavoltage photon beams. A particularly important feature is its good angular response in the MV range. They would be good candidates for in vivo dosimetry, and quality assurance of VMAT and tomotherapy, and other modalities with beams irradiating from multiple orientations, such as Cyberknife and ViewRay, with minor modifications.

Inverse cascades sustained by the transfer rate of angular momentum in a 3D turbulent flow.

The existence of energy cascades as signatures of conserved magnitudes is one of the universal characteristics of turbulent flows. In homogeneous 3D turbulence, the energy conservation produces a direct cascade from large to small scales, although in 2D, it produces an inverse cascade pointing towards small wave numbers. In this Letter, we present the first evidence of an inverse cascade in a fully developed 3D experimental turbulent flow where the conserved magnitude is the angular momentum. Two counterrotating flows collide in a central region where very large fluctuations are produced, generating a turbulent drag that transfers the external torque between different fluid layers.

Impact of time-dependent nonaxisymmetric velocity perturbations on dynamo action of von Kármán-like flows.

We present numerical simulations of the kinematic induction equation in order to examine the dynamo efficiency of an axisymmetric von Kármán-like flow subject to time-dependent nonaxisymmetric velocity perturbations. The numerical model is based on the setup of the French von Kármán-sodium dynamo (VKS) and on the flow measurements from a water experiment conducted at the University of Navarra in Pamplona, Spain. The principal experimental observations that are modeled in our simulations are nonaxisymmetric vortexlike structures which perform an azimuthal drift motion in the equatorial plane. Our simulations show that the interactions of these periodic flow perturbations with the fundamental drift of the magnetic eigenmode (including the special case of nondrifting fields) essentially determine the temporal behavior of the dynamo state. We find two distinct regimes of dynamo action that depend on the (prescribed) drift frequency of an (m=2) vortexlike flow perturbation. For comparatively slowly drifting vortices we observe a narrow window with enhanced growth rates and a drift of the magnetic eigenmode that is synchronized with the perturbation drift. The resonance-like enhancement of the growth rates takes place when the vortex drift frequency roughly equals the drift frequency of the magnetic eigenmode in the unperturbed system. Outside of this small window, the field generation is hampered compared to the unperturbed case, and the field amplitude of the magnetic eigenmode is modulated with approximately twice the vortex drift frequency. The abrupt transition between the resonant regime and the modulated regime is identified as a spectral exceptional point where eigenvalues (growth rates and frequencies) and eigenfunctions of two previously independent modes collapse. In the actual configuration the drift frequencies of the velocity perturbations that are observed in the water experiment are much larger than the fundamental drift frequency of the magnetic eigenmode that is obtained from our numerical simulations. Hence, we conclude that the fulfillment of the resonance condition might be unlikely in present day dynamo experiments. However, a possibility to increase the dynamo efficiency in the VKS experiment might be realized by an application of holes or fingers on the outer boundary in the equatorial plane. These mechanical distortions provoke an anchorage of the vortices at fixed positions thus allowing an adjustment of the temporal behavior of the nonaxisymmetric flow perturbations.

Intensity modulated dose calculation with an improved experimental pencil-beam kernel.

PURPOSE: This article presents an improved pencil-beam dose calculation formalism based on an experimental kernel obtained by deconvolution. The new algorithm makes it possible to calculate the absorbed dose for all field sizes. METHODS: The authors have enhanced their previous work [J. D. Azcona and J. Burguete, Med. Phys. 35, 248-259 (2008)] by correcting the kernel tail representing the contribution to the absorbed dose far from the photon interaction point. The correction was performed by comparing the calculated and measured output factors. Dose distributions and absolute dose values calculated using the new formalism have been compared to measurements. The agreement between calculated and measured dose distributions was evaluated according to the gamma-index criteria. In addition, 35 individual intensity-modulated radiation therapy (IMRT) fields were calculated and measured in polystyrene using an ionization chamber. Furthermore, a series of 541 IMRT fields was calculated using the algorithm proposed here and using a commercial IMRT optimization and calculation software package. Comparisons were made between the calculations at single points located at the isocenter for all the beams, as well as between beams grouped by anatomic location. RESULTS: The percentage of points passing the gamma-index criteria (3%, 3 mm) when comparing calculated and measured dose distributions is generally greater than 99% for the cases studied. The agreement between the calculations and the experimental measurements generally lies in the +/- 2% interval for single points, with a mean value of 0.2%. The agreement between calculations using the proposed algorithm and using a commercial treatment planning system is also between +/- 5%. CONCLUSIONS: An improved algorithm based on an experimental pencil-beam kernel obtained by deconvolution has been developed. It has been validated clinically and promises to be a valuable tool for IMRT quality assurance as an independent calculation system for monitor units and dose distributions. An important point is that the algorithm presented here uses an experimental kernel, which is therefore independent of Monte-Carlo-calculated kernels.

A system for intensity modulated dose plan verification based on an experimental pencil beam kernel obtained by deconvolution.

The number of intensity modulated radiation therapy (IMRT) procedures is continuously growing worldwide and it is necessary to develop tools for patient specific quality assurance (QA) that avoid using machine time that could be employed in treating additional patients. One way of achieving this goal is to perform a multileaf collimator quality assurance periodically in the linear accelerator and check the treatment planning system (TPS) calculation by employing an independent calculation system. Within the work frame of the pencil beam kernel approach, a new system was developed for obtaining an experimental kernel. This new technique is based on a deconvolution procedure using the Hankel transform. The resulting kernel is obtained in a way completely independent of those employed in commercial treatment planning systems, usually calculated by Monte Carlo simulations. Also provided are comparisons between calculated and measured doses with radiographic film, linear array of diodes, and ionization chamber. Measurements taken in polystyrene and water for clinical IMRT plans demonstrate that this method can calculate IMRT dose distributions, as well as treatment times, with great accuracy. Apart from other applications, it can be used as a double-check algorithm for IMRT QA.

Entrainment of a spatially extended nonlinear structure under selective forcing.

The response of a nonlinear state to a variable forcing periodic in space is studied in an extended dynamical system consisting of a liquid crystal layer driven to convection. Both the statics and the dynamics of the entrainment and the locking effects are analyzed. The dynamics of the evolution are controlled by topological singularities that allow a diffusion of the phase. The mechanisms involved are related to the role of the defects in systems undergoing spontaneous symmetry breakings.