Partial Irradiation Research Articles

Shifting the Immune-Suppressive to Predominant Immune-Stimulatory Radiation Effects by SBRT-PArtial Tumor Irradiation Targeting HYpoxic Segment (SBRT-PATHY).

Simple SummaryThis review presents and summarizes the key components and outcomes of a novel, unconventional radiation approach aimed to exploit immune-stimulatory radiation effects which, being added to direct radiation tumor cell killing, may improve the therapeutic ratio of radiotherapy. This technique, as a product of translational oncology research, was intentionally developed for the induction of immune-mediated bystander and abscopal effects in the treatment of unresectable bulky tumors which have much fewer therapeutic options and show poor prognoses after conventional treatments. This review offers insights into a unique unconventional radiotherapy technique which, due to its higher immunogenic potential, may improve the prognosis of patients affected by highly complex malignancies, providing additional opportunities for future research in terms of combining novel immuno-modulating agents with more modern radiotherapy approaches.Radiation-induced immune-mediated abscopal effects (AE) of conventional radiotherapy are very rare. Whole-tumor irradiation leads to lymphopenia due to killing of immune cells in the tumor microenvironment, resulting in immunosuppression and weak abscopal potential. This limitation may be overcome by partial tumor irradiation sparing the peritumoral immune-environment, and consequent shifting of immune-suppressive to immune-stimulatory effect. This would improve the radiation-directed tumor cell killing, adding to it a component of immune-mediated killing. Our preclinical findings showed that the high-single-dose irradiation of hypoxic tumor cells generates a stronger bystander effect (BE) and AE than the normoxic cells, suggesting their higher “immunogenic potential”. This led to the development of a novel Stereotactic Body RadioTherapy (SBRT)-based PArtial Tumor irradiation targeting HYpoxic segment (SBRT-PATHY) for induction of the immune-mediated BE and AE. Encouraging SBRT-PATHY-clinical outcomes, together with immunohistochemical and gene-expression analyses of surgically removed abscopal-tumor sites, suggested that delivery of the high-dose radiation to the partial (hypoxic) tumor volume, with optimal timing based on the homeostatic fluctuation of the immune response and sparing the peritumoral immune-environment, would significantly enhance the immune-mediated anti-tumor effects. This review discusses the current evidence on the safety and efficacy of SBRT-PATHY in the treatment of unresectable hypoxic bulky tumors and its bystander and abscopal immunomodulatory potential.

Comparative metabolic profiles of total and partial body radiation exposure in mice using an untargeted metabolomics approach.

A large scale population exposure to ionizing radiation during intentional or unintentional nuclear accidents undoubtedly generates a complex scenario with partial-body as well as total-body irradiated victims. A high throughput technique based rapid assessment method is an urgent necessity for stratification of exposed subjects independent of whether exposure is uniform total-body or non-homogenous partial-body. Here, we used Nuclear Magnetic Resonance (NMR) based metabolomics approach to compare and identify candidate metabolites differentially expressed in total and partially irradiated mice model. C57BL/6 male mice (8-10weeks) were irradiated total-body or locally to thoracic, hind limbor abdominal regions with 10Gy of gamma radiation. Urine samples collected at 24h post irradiation were examined using high resolution NMR spectroscopy and the datasets were analysed using multivariate analysis. Multivariate and metabolic pathway analysis in urine samples collected at 24h post-radiation exhibited segregation of all irradiated groups from controls. Metabolites associated with energy metabolism, gut flora metabolism and taurine were common to partial and total-body irradiation, thus making them potential candidates for radiation exposure. Nevertheless, a distinct metabolic pattern was observed in partial-body exposed groups with maximum changes observed in the hind limb region indicating differential tissue associated radiation sensitivity. The organ-specific changes may provide an early warning regarding the physiological system at risk after radiation injury. The study affirms potentiality of metabolite markers and comparative analysis could be an important piece of information for an integrated solution to a complex research question in terms of radiation biomarkers.

Biological Guided Carbon-Ion Microporous Radiation to Tumor Hypoxia Area Triggers Robust Abscopal Effects as Open Field Radiation.

Recently, a growing number of studies focus on partial tumor irradiation to induce the stronger non-target effects. However, the value of partial volume carbon ion radiotherapy (CIRT) targeting hypoxic region of a tumor under imaging guidance as well as its effect of inducing radiation induced abscopal effects (RIAEs) have not been well investigated. Herein, we developed a technique of carbon ion microporous radiation (CI-MPR), guided by 18F-FMISO PET/computerized tomography (CT), for partial volume radiation targeting the hypoxia area of a tumor and investigated its capability of inducing abscopal effects. Tumor-bearing mice were inoculated subcutaneously with breast cancer 4T1 cells into the flanks of both hind legs of mouse. Mice were assigned to three groups: group I: control group with no treatment; group II: carbon ion open field radiation (CI-OFR group) targeting the entire tumor; group III: partial volume carbon ion microporous radiation (CI-MPR group) targeting the hypoxia region. The tumors on the left hind legs of mice were irradiated with single fraction of 20 Gy of CIRT. Mice treated with CI-MPR or CI-OFR showed that significant growth delay on both the irradiated and unirradiated of tumor as compared to the control groups. Tumor regression of left tumor irradiated with CI-OFR was more prominent as compared to the tumor treated with CI-MPR, while the regression of the unirradiated tumor in both CI-MPR and CI-OFR group was similar. Biological-guided CIRT using the newly developed microporous technique targeting tumor hypoxia region could induce robust abscopal effects similar to CIRT covering the entire tumor.

Probing spatiotemporal fractionation on the preclinical level

In contrast to conventional radiotherapy, spatiotemporal fractionation (STF) delivers a distinct dose distribution in each fraction. The aim is to increase the therapeutic window by simultaneously achieving partial hypofractionation in the tumour along with near uniform fractionation in normal tissues. STF has been studied in silico under the assumption that different parts of the tumour can be treated in different fractions. Here, we develop an experimental setup for testing this key assumption on the preclinical level using high-precision partial tumour irradiation in an experimental animal model. We further report on an initial proof-of-concept experiment. We consider a reductionist model of STF in which the tumour is divided in half and treated with two complementary partial irradiations separated by 24 h. Precise irradiation of both tumour halves is facilitated by the image-guided small animal radiation research platform X-RAD SmART. To assess the response of tumours to partial irradiations, tumour growth experiments are conducted using mice carrying syngeneic subcutaneous tumours derived from MC38 colorectal adenocarcinoma cells. Tumour volumes were determined daily by calliper measurements and validated by CT-volumetry. We compared the growth of conventionally treated tumours, where the whole tumour was treated in one fraction, to the reductionist model of STF. We observed no difference in growth between the two groups. Instead, a reduction in the irradiated volume (where only one half of the tumour was irradiated) resulted in an intermediate response between full irradiation and unirradiated control. The results obtained by CT-volumetry supported the findings of the calliper-derived measurements. An experimental setup for precise partial tumour irradiation in small animals was developed, which is suited to test the assumption of STF that complementary parts of the tumour can be treated in different fractions on the preclinical level. An initial experiment supports this assumption, however, further experiments with longer follow-up and varying fractionation schemes are needed to provide additional support for STF.

SBRT-Partial Tumor Irradiation for The Treatment of Unresectable Bulky NSCLC

to report on the improved therapeutic ratio by partial tumor irradiation exploiting the bystander (BE) and abscopal effects (AE) for the treatment of bulky NSCLC. Unlike conventional (whole tumor + CTV + PTV) RT, in order to generate predominant immune-mediated tumor cell killing by radiation, we developed SBRT-PArtial Tumor irradiation targeting HYpoxic segment (SBRT-PATHY) while sparing and preserving the functionality of peritumoral immune microenvironment (PIM) and the regional lymphocytes necessary to mediate BE/AE. Our preclinical studies showed that the hypoxic tumor sub-volume if selectively irradiated was the “most-abscopal one” with highest inductive abscopal potential compared with normoxic segment. Our hypothesis is that SBRT-PATHY can improve the therapeutic ratio of unresectable bulky NSCLC by exploiting BE and AE. The primary endpoint was bulky tumor control rate. The secondary endpoints included AE rate, survival and toxicity. 20 patients with inoperable stage IIIB/IV bulky NSCLC considered unsuitable for conventional RT-chemotherapy due to comorbidities or tumor site and size were included. Combination of CT and 18F-FDG-PET was used per institutional protocol to define the hypovascularized (contrast-hypo-enhanced) and hypometabolic (SUV max < 3) tumor segment which was irradiated with 10Gy × 3 to the 70%-isodose. PIM was contoured as 1cm large peritumoral tissue that was spared from radiation (applied dose constraints: Dmin<1Gy/fraction, Dmax<5Gy/fraction, Dmean<3Gy/fraction). Immunohistochemistry and gene expression analysis were performed on the available tissue samples of 3 patients submitted to surgery following SBRT-PATHY in order to extract responding partially irradiated and unirradiated-abscopal tumor lesions. Median follow up was 12.9 months (range: 4-27). Mean bulky diameter was 8.4 cm (range: 6-14.5). On an average, the irradiated volume corresponded to 32% of the total tumor volume. The bulky tumor control rate was 95% (average bulky shrinkage 71%). AE was observed in 46% of patients. Overall, cancer-specific and progression-free survival were 55%, 75% and 65%, respectively. Multi-variate analysis for cancer specific survival was significant for SBRT-PATHY independent of age, sex, performance status, histology, stage, bulky site and volume (p < 0.001). 6 patients experienced fatigue grade 1. An effective antitumor immune response was activated in radiation-spared PIM leading to cell death of the partially irradiated tumors. CD20+ B-lymphocytes, CD3+/CD8+ T-lymphocytes densely infiltrated PIM and the border of the partially irradiated tumors. Apoptotic abscopal tumor sites showed a strong expression of the cell death-inducing cytokines, TGF-beta and FAS ligand and to a lesser degree of TRAIL and TNF-alpha. SBRT-PATHY for unresectable bulky NSCLC showed inspiring results that may potentially enhance the radiotherapy therapeutic ratio. A larger prospective trial is ongoing.

A Novel Mouse Model to Study Image-Guided, Radiation-Induced Cardiac Injury and Identify Clinically Relevant Predictors of Toxicity

Radiation (RT)-induced cardiac injury is a significant concern in thoracic oncology patients. The aim of this study was to develop a novel mouse model for RT-induced cardiotoxicity, which could be used to identify molecular pathophysiology and clinically-targetable biomarkers of disease development. We hypothesized that partial heart +/- lung RT would elicit dose-dependent cardiac dysfunction, perfusion deficits, inflammation, and vascular injury. Female C57BL/6 mice aged 9-11 weeks were administered an intravenous contrast agent (fenestraVC, ART Advanced Research Technologies, Saint-Laurent, Q) to visualize the heart on cone-beam computed tomography imaging using the Small Animal Radiation Research Platform. A single dose of photon RT at 0, 20, 40, or 60 Gy was delivered to the cardiac apex +/- lung using a 3x3 mm collimator and stereotactic body RT, and gamma-H2AX staining was used to confirm targeting. Quantitative echocardiography and single positron emission computed tomography (SPECT) with Technicium-99 sestamibi were implemented to evaluate myocardial function and perfusion respectively. Cardiac tissue and plasma were collected for multiparametric analysis of biochemical markers of RT injury and tissue was harvested for histologic analysis. RT resulted in dose-dependent systolic and diastolic dysfunction as measured by regional hypokinesis, decreased left ventricular ejection fraction (LVEF) (p = 0.0001, 60 Gy), and increased E/E’ (ratio between early mitral inflow velocity and mitral annular early diastolic velocity) (p = 0.002, 60 Gy) on echocardiography 8 weeks post-RT. Compared to control, apical perfusion deficits were noted on SPECT 8 weeks post-RT only at a dose of 60 Gy, with quantitative analysis revealing a reduction in tracer uptake regionally (p = 0.003, 60 Gy) and globally (nonsignificant). At 2 weeks post-RT, increases in troponin T (TnT), placental growth factor (PLGF), interleukin (IL)-6, IL-10, and tumor necrosis factor alpha (TNFa) were observed in irradiated cardiac tissue or plasma, with more pronounced increases in all cytokine levels post 40 Gy partial heart and lung RT compared to 60 Gy partial heart RT alone. Histology demonstrated perivascular fibrosis (p<0.05) and vessel lumen narrowing. A mouse model of RT-induced cardiotoxicity can be generated by the in-situ focal irradiation of the heart, and can be used to integrate radiomic and biochemical markers of cardiotoxicity to inform early therapeutic intervention.Abstract 3256; TableSelect radiologic and biochemical dataPartial heart RT dose (Gy)LVEF (%)E/E’Lateral wall apical uptake on SPECT#TnT#PLGF#IL-2#IL-6#IL-10#TNFa#067.328.2-------4062.2*33.30.710.93.6***----6053.5***36.4**0.65**2.0**15.5**1.41.73.91.8*40+lung63.831.10.543.8*8.31.85.8*8.7*3.8*#Values normalized to 0 Gy *P < 0.05; **P < 0.005; ***P < 0.0005. Open table in a new tab

Palliative Irradiation of Sacral Metastases: Must the Entire Bone Be Treated?

The sacrum as radiation target, raises a conceptual question: should the structure be regarded as a single unit or 5 distinct bones. If the entire sacrum must be irradiated there is a higher risk of rectal morbidity. Images of 53 patients with sacral metastases were reviewed. The extent of sacral involvement was documented. The location of the rectum was recorded relative to the individual sacral bones. In 37.7% only S1 and S2 were involved by metastatic disease. In 41.5% there was metastatic involvement of S1-S3. In 1 patient there was involvement of S5 only. In 10 cases the entire sacrum was infested by metastatic disease. The rectum never extended to the height of S1. In 38% the upper pole of the rectum reached the S3 level. In toto, there were 64.2% where the inferior extension of sacral metastatic involvement did not overlap the upper pole of the rectum. Palliation of pain was achieved in 19/20 patients treated with partial sacral irradiation. The distal part of the sacrum is rarely involved in the metastatic process. Avoidance of radiation therapy to the lower sacrum simultaneously enables effective palliation and sparing of the adjacent rectum.

Abscopal Effect of Partial Versus Whole Tumor Irradiation With Anti-CD40 in Pancreas and Lung Tumor Mouse Models

Abscopal Effect of Partial Versus Whole Tumor Irradiation With Anti-CD40 in Pancreas and Lung Tumor Mouse Models

Post Radiation Cortical Thickness Variations In Brain "Association Areas"

Higher order cognitive functions (attention and memory) performed by “association cortex” decline more compared to basic somatosensory defects performed by motor cortex to fractionated RT. Authors sought to evaluate the regional vulnerability subserving the higher order cognition to fractionated RT using Quantitative MRI. This retrospective single center study encompassed a cohort of 25 brain tumor patients treated using fractionated partial brain irradiation & underwent standard high-resolution volumetric MR protocol (T1-weighted; T2 FLAIR) pre-RT and one-year post-RT start (9-15 months). Semi-automated free surfer software was used to segment anatomic regions of the cerebral cortex for each patient. Mean Cortical thickness was measured for each region pre-RT and at one year. MRI voxels falling within 5mm of Gross tumor volume were excluded. Two higher-order cortical regions of interest (ROIs) were tested for association between radiation dose and cortical thinning: entorhinal (memory) and inferior parietal (attention/memory). For comparison, two primary cortex ROIs were also tested: pericalcarine (vision) and paracentral lobule (somatosensory/motor). Radiation dose data were projected onto the pre-RT cortical surface using FreeSurfer, and mean radiation dose was also calculated for each cortical region. The relationship of mean radiation dose and mean cortical thickness change was assessed by univariate linear regression for all instances of right or left entorhinal cortex & primary cortex areas in the patient cohort. All “association cortex” regions of interest (entorhinal or inferior parietal) that received greater than 40 Gy mean dose were tested for significant cortical thickness change via Student’s t-test. Cortical thinning was significantly associated with mean radiation dose for the entorhinal cortex (p = 0.01) and inferior parietal cortex (p = 0.02), both association cortex ROIs. Primary cortex ROIs showed no significant cortical thinning regardless of whether they received a high (>40 Gy) or low (<20 Gy) radiation dose. In the whole-cortex analysis, regions showed significant radiation dose-dependent atrophy, including areas responsible for memory, attention, and executive function (p≤0.002). Areas of cerebral cortex most vulnerable to radiation-related atrophy includes those performing higher-order cognition in brain "association areas ” thus leading to deficits in domains of memory, executive function, and attention.

Influence of particle rotation and partial irradiation on the particle heating up process

Particle heat transfer is important for the particle heating and combustion in solid fuels combustion reactors. A 3D particle conduction model is developed to investigate the mutual interactions of the partial surface irradiation and rotation speed on the particle heat transfer. The effects of particle diameter, thermal conductivity and particle shape are investigated. The lumped parameter (0D) model is also validated to determine its accuracy. Particle temperature contours, maximum, minimum and average temperatures are presented and analyzed in detail. Partial surface irradiation leads to non-uniform temperature distribution within the particle, especially for larger particles, while particle rotation tends to decrease the non-uniformity.

FLASH Investigations Using Protons: Design of Delivery System, Preclinical Setup and Confirmation of FLASH Effect with Protons in Animal Systems.

Extremely high-dose-rate irradiation, referred to as FLASH, has been shown to be less damaging to normal tissues than the same dose administrated at conventional dose rates. These results, typically seen at dose rates exceeding 40 Gy/s (or 2,400 Gy/min), have been widely reported in studies utilizing photon or electron radiation as well as in some proton radiation studies. Here, we report the development of a proton irradiation platform in a clinical proton facility and the dosimetry methods developed. The target is placed in the entry plateau region of a proton beam with a specifically designed double-scattering system. The energy after the double-scattering system is 227.5 MeV for protons that pass through only the first scatterer, and 225.5 MeV for those that also pass through the second scatterer. The double-scattering system was optimized to deliver a homogeneous dose distribution to a field size as large as possible while keeping the dose rate >100 Gy/s and not exceeding a cyclotron current of 300 nA. We were able to obtain a collimated pencil beam (1.6 × 1.2 cm2 ellipse) at a dose rate of ∼120 Gy/s. This beam was used for dose-response studies of partial abdominal irradiation of mice. First results indicate a potential tissue-sparing effect of FLASH.

Optimization of light-dependent resistor sensor for the application of solar energy tracking system

Optimization of cadmium sulfide light-dependent resistor (CdS-LDR) sensor is one of the suitable circuit elements to be used as the sun-pointing sensor. The sun-pointing sensor is used in solar energy tracking systems to capture maximum power by photovoltaic (PV) cells or systems at the time of uniform or partial irradiance of the sun and effect of shade during clouds. PV cells or modules’ generating power is affected due to partial shading. The PV cells are able to produce maximum power, as long as the sun’s irradiance is projected perpendicular to the panel’s surface. Optimization of light-dependent resistor CdS-LDR sensor is designed based on the intensity of the sun. A relation is obtained between intensity and photo-resistance of CdS-LDR sensor with coefficient of regression ( $${R}^{2}$$ ) value of 0.99. Maximum intensity of the sun is captured using CdS-LDR sensor which is designed with characteristic curve of intensity and photo-resistance using power algorithm. Minimum dull intensity of the sunlight is used to place the panel in initial position. In addition to that cloud effects with sudden transients are also analyzed using temperature humidity index term. The power gained by optimized dual axis solar tracking (DAST) system is 50.63% with reference to fixed panel. The generated power of DAST system is also analyzed under shading effect of cloud. Data are collected for every 2–3 s of time interval from 6:32:00 to 17:38:33 using real-time virtual instrumentation Parallax Data Acquisition tool.

Pilot study of neurologic toxicity in mice after proton minibeam therapy

Proton minibeams (MBs) comprised of parallel planar beamlets were evaluated for their ability to spare healthy brain compared to proton broad beams (BBs). Juvenile mice were given partial brain irradiation of 10 or 30 Gy integral dose using 100 MeV protons configured either as BBs or arrays of 0.3-mm planar MBs spaced 1.0 mm apart on center. Neurologic toxicity was evaluated during an 8-month surveillance: no overt constitutional or neurologic dysfunction was noted for any study animals. Less acute epilation was observed in MB than BB mice. Persistent chronic inflammation was noted along the entire BB path in BB mice whereas inflammation was confined to just within the MB peak regions in MB mice. The potential neurologic sparing, possibly via reduced volume of chronic inflammation, offers a compelling rationale for clinical advancement of this proton technique.

Radiotherapy Dose and Volume De-escalation in Ocular Adnexal Lymphoma.

Modern radiotherapy (RT) technique and therapy de-escalation have led to encouraging results in lymphoma management. In this study, we aimed to describe the oncological and toxicity outcome in patients with ocular adnexal lymphoma. A total of 45 patients with 52 orbital lesions who were treated at our Institution between 2003 and 2019 were considered. Clinical characteristics, treatment outcomes, and toxicity were assessed. Patients receiving 4-6 Gy were categorized as receiving ultra-low-dose RT, 24-30.6 Gy as standard-dose RT, and >30.6 Gy as high-dose RT. The predominant histological subtype was marginal zone lymphoma in 39 lesions (75%). Radiation dose ranged from 4-50.4 Gy. In the whole cohort, 11% of the lesions were treated with ultra-low-dose RT, 33% with standard-dose RT, and 56% with high-dose RT; 60% of lesions were treated using intensity-modulated RT (IMRT), while 44% of lesions were treated with partial orbital RT. The median duration of follow-up was 33 months. The overall response rate was 94% (complete response rate=83%). The 5-year local control rate, progression-free survival, and overall survival were 100%, 76%, and 92%, respectively. We did not detect any significant difference in progression-free or overall survival regarding different radiation doses and volumes. Ultra-low-dose RT was associated with a significantly lower rate of grade 2 late toxicities (0% vs. 6% and 31%, p=0.05) in comparison with standard-dose and high-dose RT, respectively. Patients who received IMRT had a significant fewer acute grade 2 (16% vs. 43%, p=0.05) and a trend towards lower late grade 2 toxicities (9% vs. 33%, p=0.06). Radiation dose and volume de-escalation seem to be safe and effective, with excellent local control and survival in the management of ocular adnexal lymphoma. IMRT seems to be associated with less toxicity.

PROLAPSE: survey about local prostate cancer relapse salvage treatment with external beam re-irradiation: results of the Italian Association of Radiotherapy and Clinical Oncology (AIRO).

We herein present the results of the first Italian Association of Radiotherapy and Clinical Oncology (AIRO) survey regarding salvage external beam re-irradiation of local prostate cancer relapse named PROLAPSE. A questionnaire with 12 items was administered to the 775 Italian radiation oncologist members of the AIRO. One hundred of the members completed the survey. The survey highlighted that 59% of the participants are currently performing prostate re-EBRT, while nearly two-thirds (65%) affirmed that they are taking into consideration the procedure in case of intraprostatic relapse. Regarding the clinical target volume (CTV), only a minority (16%) declared to always prefer the partial prostate re-irradiation, while a consistent portion (nearly two-thirds) relied on clinical considerations of the choice towards partial or whole gland irradiation. The main techniques used for re-irradiation resulted to be intensity-modulated RT (IMRT)/volumetric modulated arc therapy (VMAT) and SBRT, having received approximately 40% of responses each. Regarding the criteria for patients' selection, more than 75% of responders agreed on the use of positron emission tomography (PET)/computed tomography (CT)-choline to exclude distant metastases and of multiparametric magnetic resonance imaging (mp-MRI) to detect intraprostatic recurrence. A sufficient timeframe (> 3 years) between primary RT and reirradiation was indicated by more than half of participants as an important driver in decision-making, while histological confirmation of the relapse was considered not essential by more than two-thirds. For the use of concomitant androgen deprivation therapy (ADT), most AIRO members (79%) agreed that the prescription should be based on a case-by-case analysis. Extreme hypofractionation (> 5 Gy/fraction) was preferred by the majority (52%) of the AIRO members. In most centers (more than 74%), the planning dose-volume constraints were generally extrapolated from the published data. In half of the cases, the interviewed responders affirmed that no major gastrointestinal (GI) and genitourinary (GU) toxicities were registered in the follow-up of their re-EBRT patients. Bladder complications represented the most commonly observed form of toxicity, with an incidence of 67%. This first AIRO survey about salvage prostate re-EBRT provides an interesting snapshot and suggests increasing interest in re-EBRT patients in Italy. Consensus about some aspects of patients' selection, the necessity of biopsy, fractionation, and highly selective techniques seems feasible, but other key points such as irradiated volume, dosimetry parameters, and hormonal treatment association need to be clarified.

Effect of non-uniform proton irradiation on the critical current of REBCO tapes

Generally, uniformly-distributed irradiation defects such as artificial pinning centers improve the critical current, I c, of REBCO tapes in strong external field. On the other hand, at self-field or low field, irradiation is not effective for improving I c. However, if non-uniform pinning center distribution similar to vortex profile is assumed, this would increase I c at selffield. Therefore, in this study, we experimentally investigated the effect of partial irradiation on I c based on the assumption. We prepared REBCO tapes irradiated with trihydrogen cations in the c-axis direction. Three different patterns of defects were examined; overall, edge-only and center-only irradiations. We measured I c at 77 K, 25 K and 15 K using the four terminal method. Results showed that, while I c was not improved after the irradiations for each pattern, I c behaviour depends on the patterns; edge-only-irradiated tapes showed the highest I c and overall irradiation caused the largest I c degradation at 77 K. However, center-only-irradiated tapes showed the lowest critical current at 25 K and 15 K which may be due to enhancement of flux pinning effect at lower temperature. Moreover, pinning centers in the edge region might be more effective to increase I c, though further investigation on the effect of non-uniform pinning centers is required.

A Unified Shape-From-Shading Approach for 3D Surface Reconstruction Using Fast Eikonal Solvers

Object shape reconstruction from images has been an active topic in computer vision. Shape-from-shading (SFS) is an important approach for inferring 3D surface from a single shading image. In this paper, we present a unified SFS approach for surfaces of various reflectance properties using fast eikonal solvers. The whole approach consists of three main components: a unified SFS model, a unified eikonal-type partial differential image irradiance (PDII) equation, and fast eikonal solvers for the PDII equation. The first component is designed to address different reflectance properties including diffuse, specular, and hybrid reflections in the imaging process of the camera. The second component is meant to derive the PDII equation under an orthographic camera projection and a single distant point light source whose direction is the same as the camera. Finally, the last component is targeted at solving the resultant PDII equation by using fast eikonal solvers. It comprises two Godunov-based schemes with fast sweeping method that can handle the eikonal-type PDII equation. Experiments on several synthetic and real images demonstrate that each type of the surfaces can be effectively reconstructed with more accurate results and less CPU running time.

COVID-19: hypofractionation in the Radiation Oncology Department during the 'state of alarm': first 100 patients in a private hospital in Spain.

During the COVID-19 pandemic, Spain declared a ‘state of alarm’ on 14 March 2020. In our Radiation Oncology Department, experienced in administering hypofractionated treatments (partial irradiation in breast cancer, moderate hypofractionation in localized prostate cancer, etc), we have increased the hypofractionated treatment indications. We are only deferring the start of non-urgent treatments such as prostate tumours under androgen deprivation or benign brain tumours which are candidates for radiosurgery such as meningiomas or acoustic neuroma.In this hypofractionation era we find that we have decreased the number of sessions per patient and that we can evaluate the last years with the fractionation index (FI) (calculated by dividing the total number of fractions administered in the department by the total number of patients treated). We have gone from 14.4 in 2018 to 13.78 in 2019, excluding brachytherapy.We report the results of the first 100 patients who have experienced radiotherapy treatment since the state of alarm (66 women and 34 men). In these patients, the FI is 12.12—lower than previous years.

Multi-Variable Perturb and Observe Algorithm for Grid-Tied PV Systems With Joint Central and Distributed MPPT Configuration

This article proposes a new control algorithm that improves the dynamic performance in distributed maximum power point tracking systems. Systems with these architectures allow to increase the photovoltaic power harvested in case of partial shading and irradiance mismatch. The classical approach adopts distributed DC/DC power electronics and control without any centralized action, which makes difficult to know whether the system is working on its optimal operating point or not. The new control algorithm presented in this paper exploits the benefits of the vectorial multi-variable perturb & observe logic and acts on the control sequence under varying irradiance conditions, reducing voltage stresses at the DC/DC converters output terminals. In addition, the matching with the DC-bus voltage control is discussed, providing a centralized control to the overall system, a fact barely addressed in literature. Simulation results and experimental measurements validate the proposed approach showing improved dynamic performance and system stability.

1-[(4-Nitrophenyl)sulfonyl]-4-phenylpiperazine treatment after brain irradiation preserves cognitive function in mice.

Normal tissue toxicity is an inevitable consequence of primary or secondary brain tumor radiotherapy. Cranial irradiation commonly leads to neurocognitive deficits that manifest months or years after treatment. Mechanistically, radiation-induced loss of neural stem/progenitor cells, neuroinflammation, and demyelination are contributing factors that lead to progressive cognitive decline. The effects of 1-[(4-nitrophenyl)sulfonyl]-4-phenylpiperazine (NSPP) on irradiated murine neurospheres, microglia cells, and patient-derived gliomaspheres were assessed by sphere-formation assays, flow cytometry, and interleukin (IL)-6 enzyme-linked immunosorbent assay. Activation of the hedgehog pathway was studied by quantitative reverse transcription PCR. The in vivo effects of NSPP were analyzed using flow cytometry, sphere-formation assays, immunohistochemistry, behavioral testing, and an intracranial mouse model of glioblastoma. We report that NSPP mitigates radiation-induced normal tissue toxicity in the brains of mice. NSPP treatment significantly increased the number of neural stem/progenitor cells after brain irradiation in female animals, and inhibited radiation-induced microglia activation and expression of the pro-inflammatory cytokine IL-6. Behavioral testing revealed that treatment with NSPP after radiotherapy was able to successfully mitigate radiation-induced decline in memory function of the brain. In mouse models of glioblastoma, NSPP showed no toxicity and did not interfere with the growth-delaying effects of radiation. We conclude that NSPP has the potential to mitigate cognitive decline in patients undergoing partial or whole brain irradiation without promoting tumor growth and that the use of this compound as a radiation mitigator of radiation late effects on the central nervous system warrants further investigation.