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At least 1,405 records · Page 78

WE-FG-BRA-02: Docetaxel Eluting Brachytherapy Spacers for Local Chemo-Radiation Therapy in Prostate Cancer

Purpose: We propose an innovative combinatorial treatment strategy of Local ChemoRadiation Therapy (LCRT) using a sustained drug delivery platform in the form of a spacer to locally radio-sensitize the prostate with Docetaxel (DTX) enabling a synergistic cure with the use of lower radiation doses. These biodegradable spacers are physically similar to the inert spacers routinely used in prostate brachytherapy but are now loaded with formulations of DTX. Methods: Spacers were loaded with ∼500µg Docetaxel (DTX) for prostate cancer studies. The implants were characterized in vitro using SEM and HPLC. The release kinetic studies were carried out in buffer (pH 6.0) at 37°C. Subcutaneous PC3 tumors were xenografted in nude mice. Prostate cancer studies were done with and without radiation using SARRP at 5Gy, 10Gy, and 15Gy. Drug-loaded implants were injected once intratumorally using an 18G brachytherapy needle. Results: The release study in vitro showed a highly sustained release for multiple weeks at therapeutically relevant doses. The monotherapy with local DTX spacer showed sustained tumor inhibition compared to empty implants and an equivalent DTX dose given systemically. At 40 days, 89% survival was observed for mice treated with DTX implants compared with 0% in all other treatment groups. The combined treatment with local DTX spacer and radiation (10Gy) showed the highest degree of tumor suppression (significant tumor growth inhibition by day 90). The control mice showed continuous tumor growth and were scarified by day 56. Groups of mice treated with DTX-spacer or radiation alone showed initial tumor suppression but growth continued after day 60. A larger experiment is ongoing. Conclusion: This approach provides localized delivery of the chemotherapeutic sensitizer directly to the tumor and avoids the toxicities associated with both brachytherapy and current systemic delivery of docetaxel. Sustained release of DTX is an effective chemotherapy option alone or in combination with radiation therapy.

60 APPLIED LIFE SCIENCES↗

Strength, toughness, and reliability of a porous glass/biopolymer composite scaffold

Abstract Development of bioactive glass and ceramic scaffolds intended for the reconstruction of large segmental bone defects remains a challenge for materials science due to the complexities involved in clinical implantation, bone–implant reaction, implant degradation and the multiple loading modes the implants subjected to. A comprehensive evaluation of the mechanical properties of inorganic scaffolds and exploration of new ways to toughen brittle constructs are critical prior to their successful application in loaded sites. A simple and widely adopted approach involves the coating of an inorganic scaffold with a polymeric material. In this work, a systematic evaluation of the influence of a biopolymer, polycaprolactone (PCL), coating on the mechanical performance of bioactive glass scaffolds was carried out. Results from this work indicate that a biopolymer PCL coating was more effective in increasing the compressive strength and reliability of the glass scaffold under compression, but less effective in improving its flexural strength or fracture toughness. This is the first report that reveals the limited successfulness of a polymer coating in improving the toughness of strong scaffolds, suggesting that new and novel ways of toughening inorganic scaffolds should be future research directions for scaffolds applied in loaded sites. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1209–1217, 2018.

Fu, Qiang↗

Percutaneous Decompression of Lumbar Spinal Stenosis with a New Interspinous Device

Objective: This study was designed to evaluate the feasibility of the implantation of a new interspinous device (Falena) in patients with lumbar spinal stenosis. The clinical outcomes and imaging results were assessed by orthostatic MR during an up to 6-month follow-up period. Methods: Between October 2008 and February 2010, the Falena was implanted at a single level in 26 patients (17 men; mean age, 69 (range, 54-82) years) who were affected by degenerative lumbar spinal stenosis. All of the patients were clinically evaluated before the procedure and at 1 and 3 months. Furthermore, 20 patients have completed a 6-month follow-up. Pain was assessed before and after the intervention using the Visual Analogue Scale score and the Oswestry Disability Index questionnaire. Orthostatic MR imaging was performed before the implantation and at 3 months to assess the correlation with the clinical outcome. Results: The mean ODI score decreased from 48.9 before the device implantation to 31.2 at 1 month (p < 0.0001). The mean VAS score decreased from 7.6 before to 3.9 (p < 0.0001) at 1 month and 3.6 at 3 months after the procedure (p = 0.0115). These values were stable at 6 months evaluation. No postimplantation major complications were recorded. MRI evaluation documented in most cases an increased size of the spinal canal area. Similarly a bilateral foraminal area improvement was found. The variation of the intervertebral space height measured on the posterior wall was not significant. Conclusions: In our preliminary experience with the Falena in a small cohort of patients, we obtained clinical and imaging results aligned to those reported with similar interspinous devices.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Comparison of 180-degree and 90-degree needle rotation to reduce wound size in PIT-injected juvenile Chinook salmon

Animal telemetry, which requires the implantation of passive transponders or active transmitters, is used to monitor and assess fish stock and conservation to gain an understanding of fish movement and behavior. As new telemetry technologies become available, studies of their effects on species of interest are imperative as is development of implantation techniques. In this study, we investigated the effects of bevel rotation (0-, 90-, 180-degree axis rotation) on wound extent, tag loss, and wound healing rates in juvenile Chinook salmon injected with an 8-gauge needle, which is required for implantation of the novel injectable Juvenile Salmon Acoustic Telemetry Systems (JSATS) acoustic transmitter or large passive integrated transponder (PIT) tags. Although the injection sites were not closed after injection (e.g., with sutures or glue), there were no mortalities, dropped tags, or indications of fungus, ulceration, and/or redness around the wound. On Day 0 and post-implantation Day 7, the 90-degree bevel rotation produced smaller wound extent than the 180-degree bevel rotation. No axis rotation (0-degrees) resulted in the PIT tag frequently misleading or falling out upon injection. The results of this study indicated the 90-degree bevel rotation was the more efficient technique, produced less wound extent. Given the wound extent compared to size of fish, we recommend researchers should consider a 90-degree rotation over the 180-degree rotation in telemetry studies. Highlights •Three degrees of needle rotation were examined for effects in Chinook salmon. •Mortality, tag loss, wound extent, healing, and infection indicators were measured. •There were no mortalities, tag loss, or indications of infection. •The 90-degree needle rotation through Day 7 produced the smallest wound extent.

acoustic telemetry↗

Feasibility of Electromagnetic Transponder Use to Monitor Inter- and Intrafractional Motion in Locally Advanced Pancreatic Cancer Patients

Purpose: The primary objective of this study was to determine the feasibility of electromagnetic transponder implantation in patients with locally advanced unresectable pancreatic cancer. Secondarily, the use of transponders to monitor inter- and intrafractional motion, and the efficacy of breath holding for limiting target motion, were examined. Methods and Materials: During routine screening laparoscopy, 5 patients without metastatic disease were implanted with transponders peri-tumorally. The Calypso System's localization and tracking modes were used to monitor inter- and intrafractional motion, respectively. Intrafractional motion, with and without breath holding, was also examined using Calypso tracking mode. Results: Transponder implantation was well tolerated in all patients, with minimal migration, aside from 1 patient who expulsed a single transponder. Interfractional motion based on mean shifts from setup using tattoos/orthogonal imaging to transponder based localization from 164 treatments was significant in all dimensions. Mean shift (in millimeters), followed by the standard deviation and p value, were as follows: X-axis: 4.5 mm (1.0, p = 0.01); Y axis: 6.4 mm (1.9, p = 0.03); and Z-axis 3.9 mm (0.6, p = 0.002). Mean intrafractional motion was also found to be significant in all directions: superior, 7.2 mm (0.9, p = 0.01); inferior, 11.9 mm (0.9, p < 0.01); anterior: 4.9 mm (0.5, p = 0.01); posterior, 2.9 mm (0.5, p = 0.02); left, 2.2 mm (0.4, p = 0.02); and right, 3.1 mm (0.6, p = 0.04). Breath holding during treatment significantly decreased tumor motion in all directions. Conclusions: Electromagnetic transponder implantation appears to be safe and effective for monitoring inter- and intrafractional motion. Based on these results a larger clinical trial is underway.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

The effect of helium on cavity swelling in dual-ion irradiated Fe and Fe-10Cr ferritic alloys

We report Ferritic-martensitic (FM) steels for in-vessel components in proposed fusion reactors are expected to suffer from high levels of displacement damage and helium (He) generation by neutron transmutation. However, a thorough understanding of the He synergistic effects on the cavity swelling in FM steels is still not well established. To gain fundamental insights into the He effect on cavity swelling, high purity Fe and Fe-10 wt.% Cr ferritic model alloys were irradiated with 8 MeV Ni ions and co-implanted He ions at 400 to 550 °C up to 30 displacements per atom (dpa) with He implantation rates of 0.1, 10 and 50 appm He/dpa. The current study focuses on the 50 appm He/dpa, 500 °C behavior vs. 0.1 and 10 appm He/dpa. Irradiation-induced defects, including cavities, dislocation loops, and dislocation networks were characterized using transmission electron microscopy (TEM). In the grain interior, a bimodal cavity size distribution was observed in the 10 and 50 appm He/dpa samples, but not for 0.1 appm He/dpa. Cavity swelling was maximized at intermediate He implantation rates of ~10 appm He/dpa for both ion-irradiated Fe and Fe-10Cr alloys. The cavity swelling behavior as a function of He implantation rate appears to be controlled by the He/dpa-dependent variation of cavity sink strengths. Treating small bubbles as biased sinks for interstitial absorption can significantly increase the ratio of biased to unbiased sink strengths (Q) and results in maximized cavity swelling for a Q ratio close to one.

36 MATERIALS SCIENCE↗

Microstructurally informed synchrotron x-ray analysis revealing helium defect transitions in ultrafine grained tungsten

The formation of insoluble gaseous defects in materials due to nuclear transmutation or ion implantation involves the diffusion of impurity atoms to form atomic defect clusters that coalesce into bubbles or cavities and ultimately degrade the material properties. Transmission electron microscopy (TEM) is limited in its ability to resolve sub-nanometer gas clusters whereas X-ray diffraction (XRD) provides information pertaining to local atomic changes. Here, in this study, helium (He) implanted ultrafine grained tungsten is explored through a multimodal defect characterization campaign combining TEM-informed Small Angle X-ray Scattering (SAXS) analysis, XRD lattice parameter measurements, and nanoscale He cluster quantification from a region of reciprocal space accessible via Wide Angle X-ray Scattering (WAXS). Moderate elevated temperature implantations are shown to produce high concentrations of sub-nanoscale He clusters and small, homogeneously distributed cavities, which collectively are linked to lattice expansion and further substantiated through complementary atomistic simulations. Increased implantation temperatures encourage the diffusion of these defects to the grain boundaries (GBs), leading to lattice relaxation and the growth of large GB cavities manifesting as bimodal size distributions in the SAXS analysis. Overall, our results demonstrate the utility of multimodal synchrotron X-ray analysis in bridging the gap between microscale He cavity quantification and atomic-scale defect analysis.

36 MATERIALS SCIENCE↗

Modeling of surface-state induced inter-electrode isolation of n -on- p devices in mixed-field and γ -irradiation environments

Position sensitive n-on-p silicon sensors will be utilized in the tracker and in the High Granularity Calorimeter (HGCAL) of the Compact Muon Solenoid (CMS) experiment at High Luminosity Large Hadron Collider (HL-LHC). The detrimental effect of the radiation-induced accumulation of positive net oxide charge on position resolution in n-on-p sensors has typically been countered by the application of isolation implants like p-stop or p-spray between n + -electrodes. In addition to the positively charged layer inside the oxide and close to the Si/SiO 2 -interface, surface damage introduced by ionizing radiation in SiO 2 -passivated silicon particle detectors includes the accumulation of trapped-oxide-charge and interface traps. A previous study of either n/γ (mixed field)- or γ-irradiated Metal-Oxide-Semiconductor (MOS) capacitors showed evidence of substantially higher introduction rates of acceptor- and donor-type deep interface traps (N it,acc/don ) in mixed-field environment. Here, in this work, an inter-pad and -strip resistance (or resistivity (ρ int )) simulation study of n-on-p sensors with and without p-stop isolation implants was conducted for both irradiation types. Higher levels of ρint showed correlation to higher densities of deep N it,acc/don , with the inter-pad isolation performance of the mixed-field irradiated sensors becoming independent of the presence of p-stop implant between the n + - electrodes up to about 100 kGy. The low introduction rates of deep N it,acc/don in γ-irradiated sensors resulted in high sensitivity of ρ int to the presence and peak doping of p-stop above the lowest dose of about 7 kGy in the study. As a consequence of the advantageous influence of radiation-induced accumulation of deep N it on the inter-electrode isolation, position sensitive n-on-p sensors without isolation implants may be considered for future HEP-experiments where the radiation is largely due to hadrons.

Akchurin, N. [Texas Tech Univ., Lubbock, TX (Unite↗

MeV Au Ion Irradiation in Silicon and Nanocrystalline Zirconia Film Deposited on Silicon Substrate

Nanocrystalline zirconia (ZrO2) film with thickness of 305 nm deposited on a silicon substrate was irradiated with 2 MeV Au ions to different fluences at different temperatures. The implanted ion profiles were measured by time-of-flight secondary ion mass spectrometry (ToF-SIMS) and simulated using the stopping and range of ions inmatter (SRIM) code, respectively. The experimental results show that a large fraction of the incident Au ions penetrates through the ZrO2 film and are deposited into the Si substrate. At the interface of ZrO2 and Si, a sudden decrease of Au concentration is observed due to the much larger scattering cross section of Au in ZrO2 than in Si. The depth profile of the Au ions is measured in both the ZrO2 films and the Si substrates, and the results show that the Au distribution profiles do not exhibit a dependence on irradiation temperature. The local Au concentration increases proportionally with the irradiation fluence, suggesting that no thermal or irradiation-induced redistribution of the implanted Au ions. However, the Au concentration in the ZrO2 films, as determined by SIMS, is considerably lower than that predicted by the SRIM results, and the penetration depth from the SIMS measurements is much deeper than that from the SRIM predictions. These observations can be explained by an overestimation of the electronic stopping power, used in the SRIM program, for heavy incident ions in light targets. Over-estimation of the heavy-ion electronic stopping power may lead to errors in local dose calculation and underestimation of the projected range of slow heavy ions in targets that contain light elements. A quick estimate based on a reduced target density may be used to compensate the overestimation of the electronic stopping power in the SRIM program to provide better ion profile prediction.

Environmental Molecular Sciences Laboratory↗

Isomer spectroscopy of neutron-rich 168 Tb 103

In-flight fission of a 345 MeV per nucleon 238U primary beam on a 2 mm thick 9Be target has been used to produce and study the decays of a range of neutron-rich nuclei centred around the doubly mid-shell nucleus 170Dy at the RIBF Facility, RIKEN, Japan. The produced secondary fragments of interest were identified event-by-event using the BigRIPS separator. The fragments were implanted into the WAS3ABI position sensitive silicon active stopper which allowed pixelated correlations between implants and their subsequent β-decay. Discrete γ-ray transitions emitted following decays from either metastable states or excited states populated following beta decay were identified using the 84 coaxial high-purity germanium (HPGe) detectors of the EURICA spectrometer, which was complemented by 18 additional cerium-doped lanthanum bromide (LaBr3) fast-timing scintillation detectors from the FATIMA collaboration. This paper presents the internal decay of a metastable isomeric excited state in the odd-odd nucleus 168Tb, which corresponds to a single proton-neutron hole configuration in the valence maximum nucleus 170Dy. These data represent the first information on excited states in this nucleus, which is the most neutron-rich odd-odd isotope of terbium (Z=65) studied to date. Nilsson configurations associated with an axially symmetric, prolate-deformed nucleus are proposed for the 168Tb ground state the observed isomeric state by comparison with Blocked BCS-Nilsson calculations.

Gamma-ray spectroscopy and nuclear isomerism↗

DNA damage and apoptosis of endometrial cells cause loss of the early embryo in mice exposed to carbon disulfide

Carbon disulfide (CS{sub 2}) may lead to spontaneous abortion and very early pregnancy loss in women exposed in the workplace, but the mechanism remains unclear. We designed an animal model in which gestating Kunming strain mice were exposed to CS{sub 2} via i.p. on gestational day 4 (GD4). We found that the number of implanted blastocysts on GD8 was significantly reduced by each dose of 0.1 LD{sub 50} (157.85 mg/kg), 0.2 LD{sub 50} (315.7 mg/kg) and 0.4 LD{sub 50} (631.4 mg/kg). In addition, both the level of DNA damage and apoptosis rates of endometrial cells on GD4.5 were increased, showed definite dose–response relationships, and inversely related to the number of implanted blastocysts. The expressions of mRNA and protein for the Bax and caspase-3 genes in the uterine tissues on GD4.5 were up-regulated, while the expressions of mRNA and protein for the Bcl-2 gene were dose-dependently down-regulated. Our results indicated that DNA damage and apoptosis of endometrial cells were important reasons for the loss of implanted blastocysts induced by CS{sub 2}. - Highlights: • We built an animal model of CS2 exposure during blastocyst implantation. • Endometrial cells were used in the comet assay to detect DNA damage. • CS2 exposure caused DNA damage and endometrial cell apoptosis. • DNA damage and endometrial cell apoptosis were responsible for embryo loss.

60 APPLIED LIFE SCIENCES↗

Enhanced Magnetization of Cobalt Defect Clusters Embedded in TiO 2-δ Films

High magnetizations are desirable for spintronic devices that operate by manipulating electronic states using built-in magnetic fields. However, the magnetic moment in promising dilute magnetic oxide nanocomposites is very low, typically corresponding to only fractions of a Bohr magneton for each dopant atom. In this study, we report a large magnetization formed by ion implantation of Co into amorphous TiO 2-δ films, producing an inhomogeneous magnetic moment, with certain regions producing over 2.5 μ B per Co, depending on the local dopant concentration. Polarized neutron reflectometry was used to depth-profile the magnetization in the Co:TiO 2-δ nanocomposites, thus confirming the pivotal role of the cobalt dopant profile inside the titania layer. X-ray photoemission spectra demonstrate the dominant electronic state of the implanted species is Co 0 , with a minor fraction of Co 2+ . The detected magnetizations have seldom been reported before and lie near the upper limit set by Hund’s rules for Co 0 , which is unusual because the transition metal’s magnetic moment is usually reduced in a symmetric 3D crystal-field environment. Low-energy positron annihilation lifetime spectroscopy indicates that defect structures within the titania layer are strongly modified by the implanted Co. We propose that a clustering motif is promoted by the affinity of the positively charged implanted species to occupy microvoids native to the amorphous host. This provides a seed for subsequent doping and nucleation of nanoclusters within an unusual local environment.

73 NUCLEAR PHYSICS AND RADIATION PHYSICS↗

Alternating magnetic fields and antibiotics eradicate biofilm on metal in a synergistic fashion

Abstract Hundreds of thousands of human implant procedures require surgical revision each year due to infection. Infections are difficult to treat with conventional antibiotics due to the formation of biofilm on the implant surface. We have developed a noninvasive method to eliminate biofilm on metal implants using heat generated by intermittent alternating magnetic fields (iAMF). Here, we demonstrate that heat and antibiotics are synergistic in biofilm elimination. For Pseudomonas aeruginosa biofilm, bacterial burden was reduced >3 log with iAMF and ciprofloxacin after 24 h compared with either treatment alone ( p < 0.0001). This effect was not limited by pathogen or antibiotic as similar biofilm reductions were seen with iAMF and either linezolid or ceftriaxone in Staphylococcus aureus . iAMF and antibiotic efficacy was seen across various iAMF settings, including different iAMF target temperatures, dose durations, and dosing intervals. Initial mechanistic studies revealed membrane disruption as one factor important for AMF enhanced antibacterial activity in the biofilm setting. This study demonstrates the potential of utilizing a noninvasive approach to reduce biofilm off of metallic implants.

59 BASIC BIOLOGICAL SCIENCES↗

A versatile apparatus for on-line emission channeling experiments

The concept and functionality of an apparatus dedicated to emission channeling experiments using short-lived isotopes on-line at ISOLDE/CERN is described. The setup is assembled in two functional blocks – (a) base stand including beam collimation, implantation and measurement chamber, cryogenic extension, and vacuum control system and (b) Panmure goniometer extension including maneuvering cradle and sample heating furnace. This setup allows for in situ implantation and sample analysis in the as-implanted state and upon cooling down to 50 K and during annealing up to 1200 K. The functionality of the setup will be illustrated with the example of establishing the lattice location of {sup 56}Mn probes implanted into GaAs.

43 PARTICLE ACCELERATORS↗

Statistical investigations on nitrogen-vacancy center creation

Quantum information technologies require networks of interacting defect bits. Color centers, especially the nitrogen vacancy (NV{sup −}) center in diamond, represent one promising avenue, toward the realisation of such devices. The most successful technique for creating NV{sup −} in diamond is ion implantation followed by annealing. Previous experiments have shown that shallow nitrogen implantation (<10 keV) results in NV{sup −} centers with a yield of 0.01%–0.1%. We investigate the influence of channeling effects during shallow implantation and statistical diffusion of vacancies using molecular dynamics and Monte Carlo simulation techniques. Energy barriers for the diffusion process were calculated using density functional theory. Our simulations show that 25% of the implanted nitrogens form a NV center, which is in good agreement with our experimental findings.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗

Hydrogen decoration of radiation damage induced defect structures

The defect complexes that are formed when protons with energies in the MeV-range were implanted into high-purity silicon were investigated. After implantation, the samples were annealed at 400 °C or 450 °C for times ranging between 15 minutes and 30 hours. The resistivity of the samples was then analyzed by Spreading Resistance Profiling (SRP). The resistivity shows minima where there is a high carrier concentration and it is possible to extract the carrier concentration from the resistivity data. Initially, there is a large peak in the carrier concentration at the implantation depth where most of the hydrogen is concentrated. For longer anneals, this peak widens as the hydrogen diffuses away from the implantation depth. Following the changes in resistivity as a function of annealing time allows us to characterize the diffusion of hydrogen through these samples. Differences in the diffusion were observed depending on whether the silicon was grown by the magnetic Czochralski (m:Cz) method or the Float zone (Fz) method.

75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND↗

Reducing the uncertainties in particle therapy

The use of fundamental Nuclear Physics in Nuclear Medicine has a significant impact in the fight against cancer. Hadrontherapy is an innovative cancer radiotherapy method using nuclear particles (protons, neutrons and ions) for the treatment of early and advanced tumors. The main goal of proton therapy is to deliver high radiation doses to the tumor volume with minimal damage to healthy tissues and organs. The purpose of this work was to investigate the dosimetric errors in clinical proton therapy dose calculation due to the presence of metallic implants in the treatment plan, and to determine the impact of the errors. The results indicate that the errors introduced by the treatment planning systems are higher than 10% in the prediction of the dose at isocenter when the proton beam is passing directly through a metallic titanium alloy implant. In conclusion, we recommend that pencil-beam algorithms not be used when planning treatment for patients with titanium alloy implants, and to consider implementing methods to mitigate the effects of the implants.

62 RADIOLOGY AND NUCLEAR MEDICINE↗