Skin dose investigations on a 0.5 T parallel rotating biplanar linac-MR using Monte Carlo simulations and measurements.

BACKGROUND: The Alberta rotating biplanar linac-MR has a 0.5 T magnetic field parallel to the beamline. When developing a new linac-MR system, interactions of charged particles with the magnetic field necessitate careful consideration of skin dose and tissue interface effects. PURPOSE: To investigate the effect of the magnetic field on skin dose using measurements and Monte Carlo (MC) simulations. METHODS: We develop an MC model of our linac-MR, which we validate by comparison with ion chamber measurements in a water tank. Additionally, MC simulation results are compared with radiochromic film surface dose measurements on solid water. Variations in surface dose as a function of field size are measured using a parallel plate ion chamber in solid water. Using an anthropomorphic computational phantom with a 2 mm-thick skin layer, we investigate dose distributions resulting from three beam arrangements. Magnetic field on and off scenarios are considered for all measurements and simulations. RESULTS: For a 20 × 20 cm2 field size, D 0.2 c c ${D_{0.2cc}}$ (the minimum dose to the hottest contiguous 0.2 cc volume) for the top 2 mm of a simple water phantom is 72% when the magnetic field is on, compared to 34% with magnetic field off (values are normalized to the central axis dose maximum). Parallel plate ion chamber measurements demonstrate that the relative increase in surface dose due to the magnetic field decreases with increasing field size. For the anthropomorphic phantom, D ∼ 0.2 c c ${D_{ \sim 0.2cc}}$ (minimum skin dose in the hottest 1 × 1 × 1 cm3 cube) shows relative increases of 20%-28% when the magnetic field is on compared to when it is off. With magnetic field off, skin D ∼ 0.2 c c ${D_{ \sim 0.2cc}}$ is 71%, 56%, and 21% for medial-lateral tangents, anterior-posterior beams, and a five-field arrangement, respectively. For magnetic field on, the corresponding skin D ∼ 0.2 c c ${D_{ \sim 0.2cc}}$ values are 91%, 67%, and 25%. CONCLUSIONS: Using a validated MC model of our linac-MR, surface doses are calculated in various scenarios. MC-calculated skin dose varies depending on field sizes, obliquity, and the number of beams. In general, the parallel linac-MR arrangement results in skin dose enhancement due to charged particles spiraling along magnetic field lines, which impedes lateral motion away from the central axis. Nonetheless, considering the results presented herein, treatment plans can be designed to minimize skin dose by, for example, avoiding oblique beams and using a larger number of fields.

Clinical reference dosimetry for the 0.5 T inline rotating biplanar Linac-MR.

BACKGROUND: The world's first clinical 0.5 T inline rotating biplanar Linac-MR system is commissioned for clinical use. For reference dosimetry, unique features to device, including an SAD = 120 cm, bore clearance of 60 cm × 110 cm, as well as 0.5 T inline magnetic field, provide some challenges to applying a standard dosimetry protocol (i.e., TG-51). PURPOSE: In this work, we propose a simple and practical clinical reference dosimetry protocol for the 0.5T biplanar Linac-MR and validated its results. METHODS: Our dosimetry protocol for this system is as follows: tissue phantom ratios at 20 and 10 cm are first measured and converted into %dd10x beam quality specifier using equations provided and Kalach and Rogers. The converted %dd10x is used to determine the ion chamber correction factor, using the equations in the TG-51 addendum for the Exradin A12 farmer chamber used, which is cross-calibrated with one calibrated at a standards laboratory. For a 0.5 T parallel field, magnetic field effect on chamber response is assumed to have no effect and is not explicitly corrected for. Once the ion chamber correction factor for a non-standard SAD (kQ,msr) is determined, TG-51 is performed to obtain dose at a depth of 10 cm at SAD = 120 cm. The dosimetry protocol is repeated with the magnetic field ramped down. To validate our dosimetry protocol, Monte Carlo (EGSnrc) simulations are performed to confirm the determined kQ,msr values. MC Simulations and magnetic Field On versus Field Off measurements are performed to confirm that the magnetic field has no effect. To validate our overall dosimetry protocol, external dose audits, based on optical simulated luminescent dosimeters, thermal luminescent dosimeters, and alanine dosimeters are performed on the 0.5 T Linac-MR system. RESULTS: Our EGSnrc results confirm our protocol-determined kQ,msr values, as well as our assumptions about magnetic field effects (kB = 1) within statistical uncertainty for the A-12 chamber. Our external dosimetry procedures also validated our overall dosimetry protocol for the 0.5 T biplanar Linac-MR hybrid. Ramping down the magnetic field has resulted in a dosimetric difference of 0.1%, well within experimental uncertainty. CONCLUSION: With the 0.5 T parallel magnetic field having minimal effect on the ion chamber response, a TPR20,10 approach to determine beam quality provides an accurate method to perform clinical dosimetry for the 0.5 T biplanar Linac-MR.

Ku-band multichannel frequency comb Doppler reflectometer on the GAMMA 10/potential control and divertor simulating experiment (PDX) tandem mirror.

A Ku-band (12-18 GHz) multichannel Doppler reflectometer (DR) has been developed in the GAMMA 10/potential control and divertor simulating experiment (PDX) tandem mirror device to improve the applicability of DR measurement for simultaneous monitoring of velocity of electron density turbulence at different locations. Our previous single-channel DR circuit has been replaced by the multichannel microwave system using a nonlinear transmission line based comb generator with heterodyne technique. The multichannel DR system has been installed in the central cell of GAMMA 10/PDX. Initial results of application to GAMMA 10/PDX plasma are presented, showing Doppler frequency shifts during an additional ion cyclotron resonance frequency heating and gas-puffing experiment.

Improvement in multipass Thomson scattering system comprising laser amplification system developed in GAMMA 10/PDX.

The multipass Thomson scattering (MPTS) technique is one of the most useful methods for measuring low-electron-density plasmas. The MPTS system increases Thomson scattering (TS) signal intensities by integrating all multipass (MP) signals and improving the TS time resolution by analyzing each pass signal. The fully coaxial MPTS system developed in GAMMA 10/potential-control and diverter-simulator experiments has a polarization-based configuration with image-relaying optics. The MPTS system can enhance Thomson scattered signals for improving the measurement accuracy and megahertz-order time resolution. In this study, we develop a new MPTS system comprising a laser amplification system to obtain continuous MP signals. The laser amplification system can improve degraded laser power and return an amplified laser to the MP system. We obtain continuous MP signals from the laser amplification system by improving the laser beam profile adjuster in gas scattering experiments. Moreover, we demonstrate that more MP signals and stronger amplified MP signals can be achieved via multiple laser injections to the laser amplification system in the developed MP system comprising a laser amplification system.

Development of a laser amplification system for the multi-pass Thomson scattering system for GAMMA 10/PDX.

The multi-pass Thomson scattering (MPTS) system is a useful technique for increasing the Thomson scattering (TS) signal intensities and improving the TS diagnostic time resolution. The MPTS system developed in GAMMA 10/PDX has a polarization-based configuration with an image relaying system. The MPTS system has been constructed for enhancing the Thomson scattered signals for the improvement of measurement accuracy and the megahertz sampling time resolution. However, in the normal MPTS system, the MPTS signal intensities decrease with the pass number because of the damping due to the optical components. Subsequently, we have developed a new MPTS system with the laser amplification system. The laser amplification system can improve the degraded laser power after six passes in the multi-pass system to the initial laser power. For the first time worldwide, we successfully obtained the continued multi-pass signals after the laser amplification system in the gas scattering experiments.

Predictors of poor sleep quality in patients with systemic lupus erythematosus.

Sleep problems are common in patients with systemic lupus erythematosus (SLE). This study aimed to examine the following: (1) predictors of sleep quality and (2) fluctuations in sleep quality in patients with SLE. Patients with SLE were recruited from three rheumatology centers in Japan. We collected demographic and clinical data and data on sleep quality as measured by the Pittsburgh Sleep Quality Index (PSQI), the Medical Outcome Study Short Form-12, and the Lupus Patient Reported Outcome Tool (LupusPRO). Fluctuations in sleep quality were examined by administering the PSQI a second time after a 2-week interval. We used multiple linear regression analysis to predict sleep quality. Of 205 patients who completed the survey, 62.9% showed poor sleep quality. The largest fluctuation in sleep quality was for "waking in the middle of the night or early morning." "LupusPRO pain/vitality" was a major predictor of poor sleep. The other significant predictors were mostly LupusPRO subscales and clinical variables and SF-12 subscales were mostly non-predictive. The majority of the participants had poor sleep quality. A lupus-specific QoL scale is important for understanding poor sleep quality in SLE patients. Symptom management appeared to play a key role in improving sleep quality.

MLL is essential for NUP98-HOXA9-induced leukemia.

Rearrangements involving the NUP98 gene resulting in fusions to several partner genes occur in acute myeloid leukemia and myelodysplastic syndromes. This study demonstrates that the second FG repeat domain of the NUP98 moiety of the NUP98-HOXA9 fusion protein is important for its cell immortalization and leukemogenesis activities. We demonstrate that NUP98-HOXA9 interacts with mixed lineage leukemia (MLL) via this FG repeat domain and that, in the absence of MLL, NUP98-HOXA9-induced cell immortalization and leukemogenesis are severely inhibited. Molecular analyses indicate that MLL is important for the recruitment of NUP98-HOXA9 to the HOXA locus and for NUP98-HOXA9-induced HOXA gene expression. Our data indicate that MLL is crucial for NUP98-HOXA9 leukemia initiation.

The Japanese LupusPRO: A cross-cultural validation of an outcome measure for lupus.

Objective This study aimed to validate the Japanese version of the LupusPRO questionnaire for use with systemic lupus erythematosus patients. Methods Participants were 205 lupus patients recruited from three rheumatology centers in Japan. Demographic data were collected and quality of life was assessed using the LupusPRO and the Short Form Health Survey-12. Disease activity was evaluated by physicians using the Systemic Lupus Erythematosus Activity Index. Some participants completed questionnaires 10-14 days after the first survey. Internal consistency reliability, test-retest reliability, content validity and convergent validity were examined, and confirmatory factor analysis was performed. Results Participants' mean age was 47.8 ± 13.6 years. Older participants scored lower on physical quality of life and higher on coping than younger participants. The LupusPRO showed satisfactory test-retest reliability ( n = 111). Test-retest reliability was lower for the mental and social aspects of quality of life, indicating fluctuations in quality of life during the two-week interval. Internal consistency reliability was good and convergent validity with the corresponding domains of the Short Form Health Survey-12 was satisfactory. Confirmatory factor analysis showed a good model fit. Conclusion The Japanese LupusPRO is a reliable and valid measure to evaluate treatment interventions for systemic lupus erythematosus.

Analysis method for Thomson scattering diagnostics in GAMMA 10/PDX.

We have developed an analysis method to improve the accuracies of electron temperature measurement by employing a fitting technique for the raw Thomson scattering (TS) signals. Least square fitting of the raw TS signals enabled reduction of the error in the electron temperature measurement. We applied the analysis method to a multi-pass (MP) TS system. Because the interval between the MPTS signals is very short, it is difficult to separately analyze each Thomson scattering signal intensity by using the raw signals. We used the fitting method to obtain the original TS scattering signals from the measured raw MPTS signals to obtain the electron temperatures in each pass.

A 60-GHz interferometer with a local oscillator integrated antenna array for divertor simulation experiments on GAMMA 10/PDX.

In conventional multichannel/imaging microwave diagnostics of interferometry, reflectometry, and electron cyclotron emission measurements, a local oscillator (LO) signal is commonly supplied to a receiver array via irradiation using LO optics. In this work, we present a 60-GHz interferometer with a new eight-channel receiver array, called a local oscillator integrated antenna array (LIA). An outstanding feature of LIA is that it incorporates a frequency quadrupler integrated circuit for LO supply to each channel. This enables simple and uniform LO supply to the receiver array using only a 15-GHz LO source and a coaxial cable transmission line instead of using an expensive 60-GHz source, LO optics, and a waveguide transmission line. The new interferometer system is first applied to measure electron line-averaged density inside the divertor simulation experimental module (D-module) on GAMMA 10/PDX tandem mirror device.

First results of electron temperature measurements by the use of multi-pass Thomson scattering system in GAMMA 10.

A multi-pass Thomson scattering (TS) has the advantage of enhancing scattered signals. We constructed a multi-pass TS system for a polarisation-based system and an image relaying system modelled on the GAMMA 10 TS system. We undertook Raman scattering experiments both for the multi-pass setting and for checking the optical components. Moreover, we applied the system to the electron temperature measurements in the GAMMA 10 plasma for the first time. The integrated scattering signal was magnified by approximately three times by using the multi-pass TS system with four passes. The electron temperature measurement accuracy is improved by using this multi-pass system.

Successful hyperbaric oxygen therapy for refractory BK virus-associated hemorrhagic cystitis after cord blood transplantation.

BK virus-associated hemorrhagic cystitis (BKV-HC) is a common and major cause of morbidity in recipients of allogeneic hematopoietic stem cell transplantation. A 32-year-old woman developed severe BKV-HC on day 24 after cord blood transplantation (CBT). Despite supportive therapies - such as hyperhydration, forced diuresis, and urinary catheterization - macroscopic hematuria and bladder irritation persisted for over a month. Hyperbaric oxygen (HBO) therapy at 2.1 atmospheres for 90 min per day was started on day 64 after CBT. Macroscopic hematuria resolved within a week, and microscopic hematuria was no longer detectable within 2 weeks. Hematuria did not recur after 11 sessions of HBO therapy, and no significant side effects were observed during or after treatment. HBO therapy could thus be useful in controlling refractory BKV-HC after CBT.

Retention of tocilizumab and anti-tumour necrosis factor drugs in the treatment of rheumatoid arthritis.

OBJECTIVES: The retention of the anti-rheumatic agent tocilizumab (TCZ) has not been well documented in patients with rheumatoid arthritis (RA). We conducted an observational study to compare the retention of TCZ and anti-tumour necrosis factor (TNF) drugs in the treatment of patients with RA. METHOD: We reviewed continuation rates and causes of discontinuation of biological agents (biologics) by assessing medical records of patients with RA who were administered biologics at our institute from September 1999 to April 2012, using the Osaka University Biologics for Rheumatic Diseases (BiRD) registry. RESULTS: A total of 401 patients were included. TCZ, infliximab (IFX), etanercept (ETN), and adalimumab (ADA) were administered to 97, 103, 143, and 58 patients, respectively. There were some differences between the baseline characteristics of the groups. The median duration (range) of TCZ, IFX, ETN, and ADA administration was 2.5 (0.1-12.6), 1.9 (0.0-7.7), 2.9 (0.0-11.3), and 1.3 (0.0-3.4) years, respectively. Continuation rates for TCZ and ETN were significantly higher than those for IFX and ADA. Multivariate analyses showed that discontinuation due to lack or loss of efficacy was significantly less common in the TCZ group than in the other groups. Discontinuation due to overall adverse events was not significantly different between treatment groups. CONCLUSION: TCZ and ETN show better retention than IFX or ADA in the treatment of RA.

A new frequency-multiplied interferometer system in the GAMMA 10 tandem mirror.

A new interferometer is installed on the west anchor cell of the GAMMA 10 tandem mirror. In GAMMA 10, we have used a heterodyne-type interferometer with a 70-GHz IMPATT oscillator and a 150-MHz oscillator for frequency modulation. The new interferometer consists of a 17.5-GHz phase locked dielectric resonator oscillator and a 37.5-MHz temperature-compensated crystal oscillator, as well as frequency multipliers. The main motivation for the new interferometer using frequency multipliers is to achieve a stable and cost effective interferometer. Direct anchor heating experiments with new anchor ion cyclotron range of frequency antennas in both the west and the east anchor cells are carried out. Density increases in both anchor cells are clearly observed using the new interferometer.

Design of the polarization multi-pass Thomson scattering system.

A novel configuration of the multi-pass Thomson scattering (TS) system is proposed to improve the time resolution and accuracy of electron temperature measurements by use of a polarization control technique. This configuration can realize a perfect coaxial multi-passing at each pass, and the number of round trips is not limited by the optical configuration. To confirm the feasibility of the new method, we installed this system in the GAMMA 10 plasma system. As a result, the integrated scattering signal of the double-pass configuration is about two times larger than that of the single-pass configuration. These results are in good agreement with the design.

Development of polarization-controlled multi-pass Thomson scattering system in the GAMMA 10 tandem mirror.

In the GAMMA 10 tandem mirror, the typical electron density is comparable to that of the peripheral plasma of torus-type fusion devices. Therefore, an effective method to increase Thomson scattering (TS) signals is required in order to improve signal quality. In GAMMA 10, the yttrium-aluminum-garnet (YAG)-TS system comprises a laser, incident optics, light collection optics, signal detection electronics, and a data recording system. We have been developing a multi-pass TS method for a polarization-based system based on the GAMMA 10 YAG TS. To evaluate the effectiveness of the polarization-based configuration, the multi-pass system was installed in the GAMMA 10 YAG-TS system, which is capable of double-pass scattering. We carried out a Rayleigh scattering experiment and applied this double-pass scattering system to the GAMMA 10 plasma. The integrated scattering signal was made about twice as large by the double-pass system.

Identification of AFAP1L1 as a prognostic marker for spindle cell sarcomas.

Spindle cell sarcomas consist of tumors with different biological features, of which distant metastasis is the most ominous sign for a poor prognosis. However, metastasis is difficult to predict on the basis of current histopathological analyses. We have identified actin filament-associated protein 1-like 1 (AFAP1L1) as a candidate for a metastasis-predicting marker from the gene expression profiles of 65 spindle cell sarcomas. A multivariate analysis determined that AFAP1L1 was an independent factor for predicting the occurrence of distant metastasis (P=0.0001), which was further confirmed in another set of 41 tumors by a quantitative mRNA expression analysis. Immunohistochemical staining using paraffin-embedded tumor tissues revealed that the metastasis-free rate was significantly better in tumors negative for AFAP1L1 (P=0.0093 by log-rank test). Knocking down the AFAP1L1 gene in sarcoma cells resulted in inhibition of the cell invasion, and forced expression of AFAP1L1 in immortalized human mesenchymal stem cells induced anchorage-independent growth and increased cell invasiveness with high activity levels of matrix metallopeptidase. Furthermore, tumor growth in vivo was accelerated in AFAP1L1-transduced sarcoma cell lines. These results suggest that AFAP1L1 has a role in the progression of spindle cell sarcomas and is a prognostic biomarker.

Urinary ß-2-microglobulin as an alternative marker for fetal inflammatory response and development of bronchopulmonary dysplasia in premature infants.

OBJECTIVE: To evaluate the clinical utility of urinary ß-2-microglobulin (B2M) at birth, an alternative to proinflammatory cytokines, as an indicative marker of fetal inflammatory response and subsequent higher risk of bronchopulmonary dysplasia (BPD) in premature infants. STUDY DESIGN: The relationship between urinary B2M at birth and the occurrence of BPD was examined in 96 premature infants with a description of perinatal backgrounds. Constructing a receiver-operating characteristic curve to determine the cutoff value of urinary B2M at birth for the development of BPD, a multivariate logistic regression analysis was performed to evaluate whether elevated urinary B2M at birth can be used as a predictor of BPD. RESULTS: BPD was diagnosed in 34% (33/96) of the infants. Neonates with BPD had a significantly higher occurrence rate of chorioamnionitis and greater levels of median urinary B2M at birth than did those without BPD. The selected cutoff value of urinary B2M at birth correlated with the development of BPD, even after adjusting for gestational age and other confounding factors. CONCLUSIONS: Elevated urinary B2M levels at birth can be used as an alternative marker of fetal inflammatory response and subsequent higher risk of BPD in premature infants.