Degenerative Temporomandibular Disorders: An Assessment of Bone Trabecular Structure Using Fractal Analysis in Digital Panoramic Radiographs.

Introduction Fractal analysis has proved to be a salient tool to quantitatively assess the qualitative changes in the bone trabeculae of patients with hyperparathyroidism, osteoporosis, and various temporomandibular disorders, including osteoarthritis (OA) and rheumatoid arthritis of temporomandibular joint (TMJ), in several previous studies. The purpose of this study was to use fractal analysis to assess alterations in the trabecular pattern of the mandibular condyle in patients with degenerative temporomandibular disorders. Materials and methods This study comprised 98 subjects with 49 subjects in the study group and 49 subjects in the control group, aged 18-50 years. Age and sex in the control group were matched to those in the case group. The subjects were assessed clinically with the Diagnostic Criteria for Temporomandibular Disorders. Digital panoramic X-ray equipment with set parameters of 70 kvp, 8 mA, and 16-second exposure duration was used to take panoramic radiographs. Fractal analysis was done and the calculated fractal dimension value was obtained using ImageJ version 1.48 software (National Institutes of Health, Bethesda, MD). The same observer used Muir and Goss's method to rate the total degenerative changes in the condylar surfaces, which were substantiated by the calculated fractal dimension value. The data were statistically analyzed. Results The results revealed a significant difference (p-value = 0.041) between the mean fractal value in the case group's (1.35) and the control group's (1.38) left sides whereas the differences in the mean fractal values between the case and control groups on the right side was not significant (p-value = 0.49). Conclusion It is recommended to use the fractal dimension value and the total degenerative severity score together to quantify degenerative changes in the TMJ OA rather than exclusively relying on fractal value.

Molecular Property Diagnostic Suite for COVID-19 (MPDSCOVID-19): an open-source disease-specific drug discovery portal.

Molecular Property Diagnostic Suite (MPDS) was conceived and developed as an open-source disease-specific web portal based on Galaxy. MPDSCOVID-19 was developed for COVID-19 as a one-stop solution for drug discovery research. Galaxy platforms enable the creation of customized workflows connecting various modules in the web server. The architecture of MPDSCOVID-19 effectively employs Galaxy v22.04 features, which are ported on CentOS 7.8 and Python 3.7. MPDSCOVID-19 provides significant updates and the addition of several new tools updated after six years. Tools developed by our group in Perl/Python and open-source tools are collated and integrated into MPDSCOVID-19 using XML scripts. Our MPDS suite aims to facilitate transparent and open innovation. This approach significantly helps bring inclusiveness in the community while promoting free access and participation in software development. Availability & Implementation: The MPDSCOVID-19 portal can be accessed at https://mpds.neist.res.in:8085/.

Corrigendum: Absolute oxygen-guided radiation therapy improves tumor control in three preclinical tumor models.

[This corrects the article DOI: 10.3389/fmed.2023.1269689.].

Absolute oxygen-guided radiation therapy improves tumor control in three preclinical tumor models.

Background: Clinical attempts to find benefit from specifically targeting and boosting resistant hypoxic tumor subvolumes have been promising but inconclusive. While a first preclinical murine tumor type showed significant improved control with hypoxic tumor boosts, a more thorough investigation of efficacy from boosting hypoxic subvolumes defined by electron paramagnetic resonance oxygen imaging (EPROI) is necessary. The present study confirms improved hypoxic tumor control results in three different tumor types using a clonogenic assay and explores potential confounding experimental conditions. Materials and methods: Three murine tumor models were used for multi-modal imaging and radiotherapy: MCa-4 mammary adenocarcinomas, SCC7 squamous cell carcinomas, and FSa fibrosarcomas. Registered T2-weighted MRI tumor boundaries, hypoxia defined by EPROI as pO2 ≤ 10 mmHg, and X-RAD 225Cx CT boost boundaries were obtained for all animals. 13 Gy boosts were directed to hypoxic or equal-integral-volume oxygenated tumor regions and monitored for regrowth. Kaplan-Meier survival analysis was used to assess local tumor control probability (LTCP). The Cox proportional hazards model was used to assess the hazard ratio of tumor progression of Hypoxic Boost vs. Oxygenated Boost for each tumor type controlling for experimental confounding variables such as EPROI radiofrequency, tumor volume, hypoxic fraction, and delay between imaging and radiation treatment. Results: An overall significant increase in LTCP from Hypoxia Boost vs. Oxygenated Boost treatments was observed in the full group of three tumor types (p < 0.0001). The effects of tumor volume and hypoxic fraction on LTCP were dependent on tumor type. The delay between imaging and boost treatments did not have a significant effect on LTCP for all tumor types. Conclusion: This study confirms that EPROI locates resistant tumor hypoxic regions for radiation boost, increasing clonogenic LTCP, with potential enhanced therapeutic index in three tumor types. Preclinical absolute EPROI may provide correction for clinical hypoxia images using additional clinical physiologic MRI.

Accessing new avenues of photonic bandgaps using two-dimensional non-Moiré geometries.

Photonic crystals (PhC) formed by 2-D non-Moiré geometries are realized in this work. Non-Moiré (NM) tiles are the contours of trigonometric functions that generate exciting shapes and geometries. Photonic bandstructure calculations reveal that 2-D NM geometries exhibit new avenues of photonic bandgaps compared to the regular circular rod-based PhCs. The band structures are anisotropic and show, intriguing orientation-dependent partial bandgaps. A few of the orientation-dependent frequency selective properties of the realized NM geometry-based PhCs are demonstrated using full-wave electromagnetic simulations. The proposed geometries are practically realizable, and in this work, we experimentally demonstrate the fabrication process using the 3-D printing technique for microwave frequencies.

Oxygen Imaging of a Rabbit Tumor Using a Human-Sized Pulse Electron Paramagnetic Resonance Imager.

PURPOSE: Spatial heterogeneity in tumor hypoxia is one of the most important factors regulating tumor growth, development, aggressiveness, metastasis, and affecting treatment outcome. Most solid tumors are known to have hypoxia or low oxygen levels (pO2 ≤10 torr). Electron paramagnetic resonance oxygen imaging (EPROI) is an emerging oxygen mapping technology. EPROI utilizes the linear relationship between the relaxation rates of the injectable OX071 trityl spin probe and the partial oxygen pressure (pO2). However, most of the EPROI studies have been limited to mouse models of solid tumors because of the instrument-size limitations. The purpose of this work was to develop a human-sized 9-mT (250 MHz resonance frequency, 60 cm bore size) pulse EPROI instrument and evaluate its performance with rabbit VX-2 tumor oxygen imaging. METHODS: A New Zealand white rabbit with a 3.2-cm VX-2 tumor in the calf muscle was imaged using the human-sized EPROI instrument and a 2.25-in. ID volume coil. The animal received a ~8-min intravenous injection of OX071 (5.2 mL total volume at 72 mM concentration) and, after 75 min, an intratumoral injection (120 µL total at 5 mM OX071 concentration) and underwent EPROI. At the end of the experiments, MRI was performed using a preclinical 9.4-T MRI system to outline the tumor boundaries. RESULTS: For the first time, a human-sized pulse EPROI instrument with a 60-cm bore size/250-MHz frequency was built and evaluated using rabbit tumor oxygen imaging. For the first time, the systemic IV injection of the oxygen-sensitive trityl OX071 spin probe was used for an animal of this size. The resulting EPROI image from the IV injection showed complete tumor coverage. The image obtained after intratumoral injection showed localized coverage in the upper lobe of the tumor, demonstrating the need for improved intratumoral injection protocol. CONCLUSIONS: This study demonstrates the performance of the world's first human-sized pulse EPROI instrument. It also demonstrates that the EPROI of larger animals can be performed using the systemic injection of a manageable amount of the spin probe. This brings EPROI one step closer to clinical applications in cancer therapies. Oxygen imaging is a platform technology, and the instrument and techniques developed here will also be useful for other clinical applications.

Distribution, annual committed effective dose, and health safety assessment of 210Po in marine biota from Kalpakkam coast, Bay of Bengal.

Seafood, intertidal biota, beach sediment, and seawater from Kalpakkam coast, Bay of Bengal were analyzed for 210Po to evaluate the internal exposure and other radiological safety aspects. Kalpakkam houses various nuclear power generation facilities on its coast. The activity concentration of 210Po was more pronounced in the intertidal organisms. Pelagic planktivorous fishes have the highest activity of the non-technogenic radionuclide, followed by the detrital feeders, benthic planktivores, benthic carnivores, and pelagic carnivore fishes. The affinity of 210Po to organic detrital matter and planktonic organisms has led to a higher accumulation of radionuclide in planktivorous fishes. Activity concentration of 210Po in seafood ranged between 1.13 ± 0.3 and 96.71 ± 1.6 Bq kg-1 (Becquerel/kilogram). In seaweeds and gastropods, it ranged from 2.09 ± 0.2 to 8.21 ± 0.6 and from 9.31 ± 0.7 to 21.58 ± 1.2 Bq kg-1, respectively. The committed effective dose (CED) of 210Po in seafood varied from 31.18 to 456.68 µSv yr-1 (microSievert/year). Radiological hazard parameters, such as activity intake, CED in consumption, of the seafood from this coast are within the acceptable levels prescribed by the International Commission on Radiological Protection and US Environmental Protection Agency.

MODELING AND EXPERIMENTS TO ESTIMATE RADON EMANATION FACTOR IN SOIL-GRAIN SIZE AND MOISTURE EFFECT.

The influence of soil grain size on its radon emanation mechanism was investigated by developing a Monte-Carlo model. The proposed model supplements the previous formulations by accounting for the effect elicited by specific surface area of the sample. The specific surface area of a sample is governed by its grain size and it strongly influences the emanation rate which is a surface phenomenon. The emanation study was further extended to include the moisture effect. Experiments were carried out with two soil samples; Soil-2 and Soil-4 collected from different terrains, to analyze the role played by moisture in the emanation mechanism. The above model was augmented with provisions to include the moisture input. The model could reproduce the experimental results. There is an abrupt increase in the emanation factor when the moisture content changes from 0 to 2%. Thereafter, the increase is gradual and finally becomes steady when the moisture level reaches 10%. Soil-2 and Soil-4 showed sizeable difference in their radon emanation factor values. This could be explained based on the parent226Ra distribution pattern which stems from the mineralogical composition of the samples. Quartz was predominantly found in Soil-2, whereas Soil-4 shows peaks corresponding to minerals namely ilmenite, Rutile and Zircon confirming relatively higher concentration of heavy minerals than Soil-2. The emanation factor values of the individual minerals reported in the literature were used to decide upon the 226Ra distribution depth and with this input the model to ascertain the experimental observations.

Continuous Erector Spinae Plane Block for Refractory Chest Wall Pain in a Patient With Metastatic Breast Cancer: A Case Report.

In this case report, we described the use of the continuous erector spinae plane (ESP) block in a patient presenting with severe chest wall pain due to terminal metastatic breast cancer. Her pain was refractory to most treatment modalities despite being on huge doses of parenteral opioids for 6 months. A single shot ESP block was initially trialed, which provided her complete pain relief. This was followed by an ESP catheter insertion and continuous infusion of local anesthetic, which helped her wean off the parenteral opioids over the next 4 days. She was discharged home with the catheter in situ, attached to a delivery pump.

A systematic review on reported outcomes and outcome measures in female idiopathic chronic pelvic pain for the development of a core outcome set.

BACKGROUND: A core outcome set (COS) is required to address inconsistencies in outcome reporting in chronic pelvic pain (CPP) trials. OBJECTIVES: Evaluation of reported outcomes and selected outcome measures in CPP trials by producing a comprehensive inventory to inform a COS. SEARCH STRATEGY: Systematic review of randomised controlled trials (RCTs) identified from Cochrane Central Register of Controlled Trials (CENTRAL), Embase and MEDLINE databases. SELECTION CRITERIA: RCTs assessing efficacy and safety of medical, surgical and psychological interventions for women with idiopathic CPP. DATA COLLECTION AND ANALYSIS: Two independent researchers extracted outcomes and outcome measures. Similar outcomes were grouped and classified into domains to produce a structured inventory. MAIN RESULTS: Twenty-four trials were identified including 136 reported outcomes and outcome measures. Rates of reporting outcomes varied (4-100%) and pelvic pain was the most frequently reported outcome (100%). All trials reported the pain domain; however, only half reported quality of life, clinical effectiveness and adverse events. No differences in outcome reporting were observed in five high-quality trials (21%). Univariate analysis demonstrated an association between quality of outcome reporting and methodological quality of studies (rs  = 0.407, P = 0.048). CONCLUSION: There is wide variation in reported outcomes and applied outcome measures in CPP trials. While a COS is being developed and implemented, we propose the interim use of commonly reported outcomes in each domain: pain (pelvic pain, dyspareunia, dysmenorrhoea), life impact (quality of life, emotional functioning, physical functioning), clinical effectiveness (efficacy, satisfaction, cost effectiveness, return to daily activities) and adverse events (surgical, perioperative observations, nonsurgical). TWEETABLE ABSTRACT: There is significant variation in outcome reporting in CPP trials. Our systematic review forms the basis for the development of a core outcome set.

Evaluation of filtration efficacy of various types of face-masks using ambient and PAO aerosols following with different sterilization methods

Due to the ongoing pandemic, various types of facemasks such as N-95, surgical mask and cloth masks are being used as an essential protective measure. The filtration efficiency of these masks were tested before and after sterilization by different methods for two flow rates conditions corresponding to normal breathe rate (20 lpm) and during sneezing (90 lpm). Sterilization techniques used here are autoclaving (30 and 60 minutes), dry oven heating (30 and 60 minutes), gamma irradiation (15 and 25 kGy), hot water washing with and without detergent and immersing in 10% concentration of liquid hydrogen peroxide for 30 minutes. As expected, the N-95 is the greatest filtering efficiency among all the other type face masks. The best method to sterilize N-95 masks without affecting its performance is by using dry heat with temperature ranging from 70-80{degrees}C. The cloth masks and surgical mask are performed more or less same for both flow conditions. As an affordable sterilization method hot water washing is highly recommended which does not deteriorate the efficiency of the masks and can be used for the general public. The use of double or triple layer cotton cloth masks in the general public serves fit for the purpose than surgical masks. The surgical mask can be sterilized only few times with the help of dry heat, hot water wash and/or autoclave.

Fabry-Pérot modes associated with hyperbolic-like dispersion in dielectric photonic crystals and demonstration of a bending angle sensor at microwave frequencies.

The dispersion properties of metamaterials and photonic crystals (PhCs) lead to an intensive research in the development of cavity resonators for the confinement of electromagnetic (e-m) radiation. In this work, we investigate the formation of Fabry-Pérot (FP) modes associated with hyperbolic-like dispersion (HLD) regimes in two-dimensional dielectric PhCs. Conventionally, FP modes are formed using an optical etalon, in which electromagnetic (e-m) waves reflecting from a partially reflecting mirror separated by a distance can interfere constructively and form a resonating mode. The FP mode observed in dielectric PhCs is formed due to the interference of cylindrical wavefronts inside the PhC interface at HLD frequencies. The FP modes in PhCs are surface localized, in which maxima/minima of the electric field lies along the air-PhC interface as a standing wave pattern and decays in air medium. Projected bandstructure, Eigen Frequency Contours (EFC), phase and group index calculations are carried out to explain the formation of FP modes in PhCs under different coupling cases. By varying the PhC dimension, FP modes with different spatial profiles are witnessed and the role of source position in exciting specific mode is demonstrated. The observed FP modes in PhCs are compared with the FP mode in an ideal indefinite slab. Based on the FP resonance in PhCs, a sensing device capable of detecting a bending angle less than [Formula: see text] is demonstrated numerically. The FP modes in PhCs are scalable to other parts of e-m spectra so that the bending angle sensing can be extendable to terahertz and optical domains.

Anisotropic asymmetric transmission of circularly polarized terahertz waves in a three-dimensional spline assembly.

Asymmetric transmission (AT) for circularly polarized (CP) electromagnetic (e-m) waves in chiral metamaterial (CMM) is a well-known phenomenon. However, most of the CMMs exhibit AT along only one direction. In this work, AT for CP waves with a magnitude of more than 0.5 along three principal directions of a newly made three-dimensional (3D) spline assembly is reported at terahertz frequencies. Surface current analysis is presented to explain the mechanism of AT for CP waves in the proposed 3D assembly.

QUANTIFICATION OF BACK DIFFUSION IN RADON AND THORON EXHALATION RATE MEASUREMENTS.

The radon (222Rn) and thoron (220Rn) fluxes from the soil and building materials are the major contributors to their indoor levels. Hence, the measurement of radon and thoron exhalation rates from the source matrix becomes the foremost step in controlling the indoor radon and thoron exposure. It is a challenge to measure the exhalation rates without disturbing the natural conditions. The back-diffusion phenomenon modifies the exhalation rate. The work presented here is to measure the back-diffusion coefficient and takes it into consideration while estimating the exhalation rate. For radon measurements, the back-diffusion coefficient and the free exhalation rates were simultaneously estimated by adopting a novel methodology. The leak rate of the experimental setup measured by this methodology was agreeable with the value measured by adopting the standard technique. In the case of thoron, the back-diffusion effect was found to be negligible for the present experimental conditions and it is duly explained. The above results were obtained by analyzing two soil samples with high 238U and 232Th content collected from monazite-rich coastal area.

The effect of DTPA on calcium carbonate scale deposition on copper and aluminium surfaces.

Calcium carbonate (CaCO3) scale inhibition by Diethylenetriaminepentaacetic acid (DTPA) on copper and aluminium metal surfaces was studied at 60 and 100 °C. The samples were characterized using X-ray diffraction (XRD), Scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR). The results revealed a novel pot like morphology for calcite which was resulted from the transformation of dumbbell morphology. The pot like morphology exposed the possibility of hollow structures for other polymorphs and is resulted from the breaking apart of the dumbbell structures at the middle, followed by fluffing of the separated parts.

Realization of Bidirectional, Bandwidth-Enhanced Metamaterial Absorber for Microwave Applications.

The ever-increasing interest towards metamaterial absorbers owes to its remarkable features such as ultra-thin nature and design flexibility. Subduing the inherent narrow bandwidth of such absorbers is the prime goal in metamaterial absorber research, as this can widen the applications areas. A greater challenge is to construct bidirectional absorber, which provides direction-insensitive absorption, as most of the existing designs exhibit single sided absorption due to the complete metal film used in the design. This work presents the realization of a bidirectional, bandwidth-enhanced metamaterial absorber with basic elements such as strips and squares optimized to have adjacent resonances leading to a bandwidth-enhanced absorption. The structural evolution of the constituent metallic components towards the formation of bandwidth-enhanced absorption is described. The bidirectional absorber exhibits more than 90% absorption between 13.40 GHz and 14.25 GHz from the two incident directions. The mechanism of absorption is studied with the surface current analysis and the effective parameters of the structure. The choice of the metallic components with four-fold rotation symmetry renders the proposed design to be polarization independent and wide-angle receptive. The numerical studies are verified experimentally at microwave frequencies, which shows a good agreement between them.

Monte Carlo simulation of an HPGe detector for detection of 239Pu in waste assay system.

This paper discusses the modeling of HPGe detector used in waste assay system using Monte Carlo code FLUKA to determine its detection limits. The modeled detector is validated using experimental point sources efficiencies in the energy range 60 keV-2000 keV. The numerical estimation of efficiency values for 239Pu present inside a 230 L cotton filled waste drum at various locations along the axis of the detector is discussed. Estimation of the minimum detectable activity (MDA) for 239Pu at these locations in the presence of 1 MBq of 137Cs/60Co again along the axis of the detector is examined. The efficiency of 239Pu decreases from 6.1 × 10-10 to 7.5 × 10-11 cps/Bq as the location of 239Pu moves away from the detector. MDA of 239Pu increases as the position of 239Pu and 137Cs/60Co in the waste drum shifts away from the detector while it decreases as the location of 137Cs/60CO moves away from 239Pu along measurement axis. It is observed that for all locations of 137Cs/60Co with 239Pu located up to 200 mm from the edge of the drum, the detection limit is within 140.3 mg (allowed limit).

Commissioning of portal dosimetry using a novel method for flattening filter-free photon beam in a nontrue beam linear accelerator.

AIM: The aim of this study is to commission and validate the portal dosimetry (PD) system using an indirect method for flattening filter free (FFF) photon beam of the upgraded c-series linear accelerator. BACKGROUND: Varian Medical System clinacs with amorphous-silicon portal imager panel (aSi-1000) do not have PD for FFF beams. Recently, our c-series linear accelerator was upgraded to deliver 6MV FFF (6MVFFF) photon beam with the highest dose rate of 1400 monitor unit (MU)/min. The study, therefore, focuses on the commissioning and validation of PD for the 6MVFFF beam. MATERIALS AND METHODS: An indirect method was implemented to predict the portal dose for FFF beam in Eclipse as the treatment planning system does not have direct prediction algorithm for FFF beam (version. 11). Dosimetrical characteristics of aSi-electronic portal imaging device (EPID) were evaluated for 6MVFFF beam and validation of PD for 6MVFFF beam was performed for open fields along with pretreatment quality assurance of intensity-modulated radiation therapy (IMRT), volumetric-modulated arc therapy (VMAT), and stereotactic radiosurgery (SRS) techniques for 30 patients planned with 6MVFFF beam. RESULTS: ASi-EPID saturates between 100 and 130 cm source to detector distance (SDD) for 6MVFFF beam and resolved at more than 140 cm SDD. The squared correlation coefficient (R2) for MU linearity was found to be 1 (R2 = 1), and instantaneous dose response linearity at different SDD's was found to be 0.999 (R2 = 0.999) for the 6MVFFF beam. Maximum gamma area index (GAI) for 3% dose difference and 3 mm distance-to-agreement criteria for IMRT, VMAT, and SRS/stereotactic radiotherapy plans was 97.9% ± 0.3%, 96.3% ± 0.5%, and 98.2% ± 0.2%, respectively. CONCLUSION: The results reveal that this novel method can be used to commission portal dosimetry for 6MVFFF beam as it is a convenient, faster, and accurate method.

Heparin-binding EGF-like growth factor (HB-EGF) antisense oligonucleotide protected against hyperlipidemia-associated atherosclerosis.

BACKGROUND AND AIMS: Heparin-binding EGF-like growth factor (HB-EGF) is a representative EGF family member that interacts with EGFR under diverse stress environment. Previously, we reported that the HB-EGF-targeting using antisense oligonucleotide (ASO) effectively suppressed an aortic aneurysm in the vessel wall and circulatory lipid levels. In this study, we further examined the effects of the HB-EGF ASO administration on the development of hyperlipidemia-associated atherosclerosis using an atherogenic mouse model. METHODS AND RESULTS: The male and female LDLR deficient mice under Western diet containing 21% fat and 0.2% cholesterol content were cotreated with control and HB-EGF ASOs for 12 weeks. We observed that the HB-EGF ASO administration effectively downregulated circulatory VLDL- and LDL-associated lipid levels in circulation; concordantly, the HB-EGF targeting effectively suppressed the development of atherosclerosis in the aorta. An EGFR blocker BIBX1382 administration suppressed the hepatic TG secretion rate, suggesting a positive role of the HB-EGF signaling for the hepatic VLDL production. We newly observed that there was a significant improvement of the insulin sensitivity by the HB-EGF ASO administration in a mouse model under the Western diet as demonstrated by the improvement of the glucose and insulin tolerances. CONCLUSION: The HB-EGF ASO administration effectively downregulated circulatory lipid levels by suppressing hepatic VLDL production rate, which leads to effective protection against atherosclerosis in the vascular wall.

Oxygen-Guided Radiation Therapy.

PURPOSE: It has been known for over 100 years that tumor hypoxia, a near-universal characteristic of solid tumors, decreases the curative effectiveness of radiation therapy. However, to date, there are no reports that demonstrate an improvement in radiation effectiveness in a mammalian tumor on the basis of tumor hypoxia localization and local hypoxia treatment. METHODS AND MATERIALS: For radiation targeting of hypoxic subregions in mouse fibrosarcoma, we used oxygen images obtained using pulse electron paramagnetic resonance pO2 imaging combined with 3D-printed radiation blocks. This achieved conformal radiation delivery to all hypoxic areas in FSa fibrosarcomas in mice. RESULTS: We demonstrate that treatment delivering a radiation boost to hypoxic volumes has a significant (P = .04) doubling of tumor control relative to boosts to well-oxygenated volumes. Additional dose to well-oxygenated tumor regions minimally increases tumor control beyond the 15% control dose to the entire tumor. If we can identify portions of the tumor that are more resistant to radiation, it might be possible to reduce the dose to more sensitive tumor volumes without significant compromise in tumor control. CONCLUSIONS: This work demonstrates in a single, intact mammalian tumor type that tumor hypoxia is a local tumor phenomenon whose treatment can be enhanced by local radiation. Despite enormous clinical effort to overcome hypoxic radiation resistance, to our knowledge this is the first such demonstration, even in preclinical models, of targeting additional radiation to hypoxic tumor to improve the therapeutic ratio.