Imaging Cherenkov emission for quality assurance of high-dose-rate brachytherapy.

With advances in high-dose-rate (HDR) brachytherapy, the importance of quality assurance (QA) is increasing to ensure safe delivery of the treatment by measuring dose distribution and positioning the source with much closer intervals for highly active sources. However, conventional QA is time-consuming, involving the use of several different measurement tools. Here, we developed simple QA method for HDR brachytherapy based on the imaging of Cherenkov emission and evaluated its performance. Light emission from pure water irradiated by an 192Ir γ-ray source was captured using a charge-coupled device camera. Monte Carlo calculations showed that the observed light was primarily Cherenkov emissions produced by Compton-scattered electrons from the γ-rays. The uncorrected Cherenkov light distribution, which was 5% on average except near the source (within 7 mm from the centre), agreed with the dose distribution calculated using the treatment planning system. The accuracy was attributed to isotropic radiation and short-range Compton electrons. The source positional interval, as measured from the light images, was comparable to the expected intervals, yielding spatial resolution similar to that permitted by conventional film measurements. The method should be highly suitable for quick and easy QA investigations of HDR brachytherapy as it allows simultaneous measurements of dose distribution, source strength, and source position using a single image.

TAZ activation by Hippo pathway dysregulation induces cytokine gene expression and promotes mesothelial cell transformation.

Malignant mesothelioma (MM) constitutes a very aggressive tumor that is caused by asbestos exposure after long latency. The NF2 tumor suppressor gene is mutated in 40-50% of MM; moreover, one of its downstream signaling cascades, the Hippo signaling pathway, is also frequently inactivated in MM cells. Although the YAP transcriptional coactivator, which is regulated by the Hippo pathway, can function as a pro-oncogenic protein, the role of TAZ, a paralog of YAP, in MM cells has not yet been clarified. Here, we show that TAZ is expressed and underphosphorylated (activated) in the majority of MM cells compared to immortalized mesothelial cells. ShRNA-mediated TAZ knockdown highly suppressed cell proliferation, anchorage-independent growth, cell motility, and invasion in MM cells harboring activated TAZ. Conversely, transduction of an activated form of TAZ in immortalized mesothelial cells enhanced these in vitro phenotypes and conferred tumorigenicity in vivo. Microarray analysis determined that activated TAZ most significantly enhanced the transcription of genes related to "cytokine-cytokine receptor interaction." Among selected cytokines, we found that IL-1 signaling activation plays a major role in proliferation in TAZ-activated MM cells. Both IL1B knockdown and an IL-1 receptor antagonist significantly suppressed malignant phenotypes of immortalized mesothelial cells and MM cells with activated TAZ. Overall, these results indicate an oncogenic role for TAZ in MMs via transcriptional induction of distinct pro-oncogenic genes including cytokines. Among these, IL-1 signaling appears as one of the most important cascades, thus potentially serving as a target pathway in MM cells harboring Hippo pathway inactivation.

Practical use of a plastic scintillator for quality assurance of electron beam therapy.

Quality assurance (QA) of clinical electron beams is essential for performing accurate and safe radiation therapy. However, with advances in radiation therapy, QA has become increasingly labor-intensive and time-consuming. In this paper, we propose a tissue-equivalent plastic scintillator for quick and easy QA of clinical electron beams. The proposed tool comprises a plastic scintillator plate and a charge-coupled device camera that enable the scintillation light by electron beams to be recorded with high sensitivity and high spatial resolution. Further, the Cerenkov image is directly subtracted from the scintillation image to discriminate Cerenkov emissions and accurately measure the dose profiles of electron beams with high spatial resolution. Compared with conventional methods, discrepancies in the depth profile improved from 7% to 2% in the buildup region via subtractive corrections. Further, the output brightness showed good linearity with dose, good reproducibility (deviations below 1%), and dose rate independence (within 0.5%). The depth of 50% dose measured with the tool, an index of electron beam quality, was within ±0.5 mm of that obtained with an ionization chamber. Lateral brightness profiles agreed with the lateral dose profiles to within 4% and no significant improvement was obtained using Cerenkov corrections. Field size agreed to within 0.5 mm with those obtained with ionization chamber. For clinical QA of electron boost treatment, a disk scintillator that mimics the shape of a patient's breast is applied. The brightness distribution and dose, calculated using a treatment planning system, was generally acceptable for clinical use, except in limited zones. Overall, the proposed plastic scintillator plate tool efficiently performs QA for electron beam therapy and enables simultaneous verification of output constancy, beam quality, depth, and lateral dose profiles during monthly QAs at lower doses of irradiation (small monitor units, MUs).

Validity and reliability of the Japanese version of the family needs survey.

Early intervention and disability services in Japan historically have focused on supporting the individual with a disability, with only secondary attention to family needs and priorities. Since the Basic Law for Persons with Disabilities was codified in 2011, the Japanese government has been responsible for supporting families with members who have disabilities. To assess the needs of these families, we evaluated the reliability and validity of the Family Needs Survey (FNS), initially developed in 1988 (Bailey & Simeonsson), to determine its usefulness for programs providing services for Japanese families who have a child with a disability. The FNS is a practical tool to assess family needs and is already used across many different cultures and populations. To evaluate the reliability and validity of the FNS, we conducted an anonymous survey with a self-administered questionnaire at 6 treatment and education institutions, 3 medical institutions mainly for children with disabilities, and 39 special needs schools in the Osaka area. We analyzed 1171 parents' survey responses: 452 fathers and 719 mothers of children with disabilities aged 0-15 years old who answered all items on the Japanese version of the FNS. Another survey was administered to 130 specialists who work with children with disabilities to assess the content validity of the Japanese version of the FNS. We verified the factor structure, content validity, and reliability of the Japanese version of the FNS as an assessment tool with 34 items among four factors that were based on the same items in the original FNS. The assessment could be used for families with school-age children as well as younger children, in contrast to the original version, which is not appropriate for school-age children. We also confirmed that it could be used without regard to type or degree of disability.