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The present study investigated the biological effects of spot scanning and passive scattering proton therapies at the distal end region of the spread-out Bragg peak (SOBP) using single cell and multicell spheroids.The Geant4 Monte Carlo simulation was used to calculate linear energy transfer (LET) values in passive scattering and spot scanning beams. The biological doses of the two beam options at various points of the distal end region of SOBP were investigated using EMT6 single cells and 0.6-mm V79 spheroids irradiated with 6 and 15 Gy, respectively, by inserting the fractions surviving these doses onto dose-survival curves and reading the corresponding dose.LET values in the entrance region of SOBP were similar between the two beam options and increased at the distal end region of SOBP, where the LET value of spot scanning beams was higher than that of passive scattering beams. Increases in biological effects at the distal end region were similarly observed in single cells and spheroids; biological doses at 2-10 mm behind the distal end were 4.5-57% and 5.7-86% higher than physical doses in passive scattering and spot scanning beams, respectively, with the biological doses of spot scanning beams being higher than those of passive scattering beams (In single cells and spheroids, the effects of proton irradiation were stronger than expected from measured physical doses at the distal end of SOBP and were correlated with LET increases.

How to select optimal cord blood (CB) remains an important clinical question. We developed and validated an index of CB engraftment, the cord blood index (CBI), which uses three weighted variables representing cell doses and HLA mismatches. We modeled the neutrophil engraftment time with competing events by random survival forests for competing risks as a function of the predictors: total nucleated cells, CD34, colony-forming units for granulocytes/macrophages, and the number of HLA mismatches at the antigen and allele levels. The CBI defined three groups that had different neutrophil engraftment rates at day 30 (High, 83.7% [95% CI, 79.2-88.1%]; Intermediate, 77.0% [95% CI, 73.7-80.2%]; Low, 68.4% [95% CI, 63.6-73.2%]), platelet engraftment rates at day 60 (High, 70.4% [95% CI, 64.9-75.9%]; Intermediate, 62.3% [95% CI, 58.5-66.0%]; Low, 49.3% [95% CI, 44.2-54.5%]), and non-relapse mortality at day 100 (High, 14.1% [95% CI, 9.9-18.3%]; Intermediate, 16.4% [95% CI, 13.5-19.3%]; Low, 21.3% [95% CI, 17.1-25.5%]). This novel approach is clinically beneficial and can be adopted immediately because it uses easily obtained pre-freeze data of CB.

This study retrospectively investigated the efficacy and safety of image-guided proton therapy (IGPT) for elderly (&ge, 80 years old) hepatocellular carcinoma (HCC) patients. Proton therapy was performed using respiratory-gated and image-guided techniques. Seventy-one elderly HCC patients were treated using IGPT. The Child&ndash, Pugh score was A5 in 49 patients, A6 in 15, and B7-9 in 7. Forty-seven patients with a peripherally located tumor were administered 66 gray relative biological effectiveness (GyRBE) in 10 fractions, whereas 24 with a centrally located tumor received 72.6 GyRBE in 22 fractions. The median follow-up period of surviving patients was 33 months (range: 9&ndash, 68). Two-year overall survival (OS) and local control (LC) rates estimated by the Kaplan&ndash, Meier method were 76% (95% confidence interval: 66&ndash, 87%) and 88% (80&ndash, 97%), respectively. According to the Common Terminology Criteria for Adverse Events version 4.0, no grade 2 or higher radiation-induced liver disease was observed, and only 1 patient developed grade 3 dermatitis. The quality of life score (European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 version 3.0, QLQ-HCC18, and SF-36) did not change after 1 year, except for the three-mental component summary (SF-36, improvement). IGPT is a safe and effective treatment for HCC in elderly patients.

Introduction In Japan, APSSM's founding president Shirai developed a silicon single rod that is inserted into the outside corpora in 1971. In the 1990s penile prostheses started to be sold in Japan. However, sales stopped in 2007. Since then, it has been up to doctors to order them individually. Objective we performed 141penile prothesis surgeries between 1992 and 2019.9. Age is 25-81 years average 62 ± 8 years old. the causes of ED are Diabetes 57 cases, arteriosclerosis (hypertension) 24 cases, failure of prosthesis surgery 17 cases, intrapelvic surgery (prostate ca, bladder Ca, rectal Ca) 16 cases, brain disease (bleeding, infarction, Parkinson, meningitis) 12 cases, Renal failure 7 cases, Peyronie ’s disease 5 cases, priapism 2 cases, wrong masturbation habit 1 case. Diabetes was the most common cause. Diagnosis is vasculogenic and neurogenic 88 cases, vasculogenic 54 cases, vasculogenic and curvature 3 cases, neurogenic 6 cases. Methods Anesthesia method is local anesthesia (penile block) 128 cases, general anesthesia 13 cases. Penile prostheses were AMS 700CXM 6 cases, Titan OTR narrow base (Coloplast) 2 case, hydroflex 1 case, AMS Dura II 26 cases, AMS 600 17 cases, Genesis (Coloplast) 84 cases, Koken (Japan) 5 cases. We have used AMS since 1992, The sale of penile protheses in Japan was halted in 2007. Since 2008, Our University doctors have been ordering Coloplast prostheses Implanted penile prosthesis size is 11-19.5cm length average 15.9cm, median 16cm. The diameter is Dura II 1cm (26 cases), AMS 600 0.95cm (15 cases) 1.15cm (2 cases), Genesis 1.1cm (28 cases), Genesis 0.95cm (56 cases). Day surgeries are popular therefore 94% of patients prefer a non-inflatable prosthesis. We devised a single-implant procedure and performed surgery for the following indications:1. Narrow cavernosum because of congenital abnomarity or re-operations. 2. Small penis. 3. Uncontrolled diabetes. 4. ED caused by corporal veno-occlusive dysfunction (CVOD) in a young man. 5. Patient preference for a warm erect penis (with a PDE5 inhibitor). Single implant surgery has a high satisfaction rate of 98% with no complications, but there are still many enlargement operations and use of PDE5 inhibitors. Results Intercourse was possible 137 cases (97.0%) and impossible 4 cases (3.0%). Ejaculation was possible 100cases (77%), impossible 32 cases (24%) (prostate or rectal surgery, retrograde ejaculation due to DM). Complication rate is 7.8%, exposure of one side prosthesis to urethra 2.8%, exposure of one side prosthesis to skin 0.7%, Exposure of tube (AMS700CXM) 0.7%, persistent pain 2.1%, infection 1.4%. Satisfaction rate is 95.0% Conclusions The penile prosthesis is still considered to be the surgical gold standard for treatment of ED. All other available treatments for ED should be compared with the results of penile prosthesis surgery. In Japan, 95% of day surgeries use non-inflatable prostheses. Disclosure Work supported by industry: no.

Background Prior ventricular tachycardia (VT) and low left ventricular ejection fraction (LVEF) are the most important prognostic factors in cardiac sarcoidosis (CS). Recently diagnosis of CS was renewed according to Japanese new guidelines. Patients with preserved cardiac function often have VT events, thus new guidelines recommends to assess the implantable cardioverter defibrillator (ICD) implantation for CS patients with preserved LVEF (35%≤LVEF Objective In CS patients with preserved LVEF, we evaluated the prognosis between VT manifestation and non-VT manifestation groups at CS diagnosis from Japanese nationwide questionnaire survey. Methods Total of 757 Japanese patients from 57 hospitals who diagnosed CS were examined. Patients who unsatisfied the criteria of the Japanese new guidelines, who had LVEF≤35%, LVEF>50%, or who underwent cardiac transplantations were excluded. 104 patients with LVEF 35–50% (67 females, mean age 60±15 years old, median follow-up periods 2134 days [interquartile range: 758–2935 days]) were analyzed. The prognosis between VT manifestation and non-VT manifestation groups at CS diagnosis were evaluated. Results 30 patients had VT manifestation at CS diagnosis and 24 patients (80%) received ICDs. 74 patients had no VT manifestation at CS diagnosis and 19 patients (44%) received ICDs during follow up period. All-cause mortality was not different between two groups (Figure). Appropriate ICD therapy of non-VT manifestation group was significantly lower compared with that of VT manifestation group (log-rank p=0.001), however considerable number (n=7, 15%) of non-VT manifestation group had appropriate ICD therapy event during follow-up period. Cox hazard analysis revealed that concomitant non-sustained VT (NSVT) with atrioventricular block (AVB) was a predictor of appropriate ICD therapy in non-VT manifestation group. Conclusion This nationwide survey showed that considerable number of CS patients with preserved LVEF had VT events, independent of VT manifestation. Concomitant NSVT with AVB was a predictor of VT events, and ICD implantation should be assessed. Funding Acknowledgement Type of funding source: None

Purpose Treatment of sinonasal malignant tumors is challenging, and evidence to establish a standard treatment is limited. Our objective was to evaluate the efficacy and safety of spot scanning proton therapy (SSPT) for sinonasal malignant tumors. Patients and Methods We retrospectively analyzed patients with sinonasal malignant tumors (T1-4bN0-2M0) who underwent SSPT between May 2014 and September 2019. The prescription dose was typically either 60 GyRBE in 15 fractions or 60.8 GyRBE in 16 fractions for mucosal melanoma and 70.2 GyRBE in 26 fractions for other histologic subtypes. Endpoints included local control (LC), progression-free survival, overall survival (OS), and incidence of toxicity. Prognostic factors were analyzed using the Kaplan-Meier method and log-rank test. Results Of 62 enrolled patients, the common histologic subtypes were mucosal melanoma (35%), squamous cell carcinoma (27%), adenoid cystic carcinoma (16%), and olfactory neuroblastoma (10%). Locally advanced stages were common (T3 in 42% and T4 in 53%). Treatment-naïve tumors and postsurgical recurrent tumors accounted for 73% and 27%, respectively. No patient had previous radiotherapy. The median follow-up was 17 months (range, 6-66) for all patients and 21.5 months (range, 6-66) for survivors. The 2-year LC, progression-free survival, and OS rates of all patients were 92%, 50%, and 76%, respectively. Univariate analysis revealed histology as a prognostic factor for OS, being higher in adenoid cystic carcinoma and olfactory neuroblastoma than in other tumors. Sixteen grade ≥3 late toxicities were observed in 12 patients (19%), including 11 events resulting in visual impairment; the most common was cataract. There was 1 grade 4 toxicity, and there were no grade 5 toxicities. Conclusion SSPT was well tolerated and yielded good LC for sinonasal malignant tumors. Although we consider SSPT to be a leading treatment modality, further studies are required to establish its status as a standard treatment.

In order to achieve the ultimate goal of reducing coincidence time resolution (CTR) to 10 ps, thus enabling reconstruction-less positron emission tomography, a Cherenkov-radiator-integrated microchannel plate photomultiplier tube (CRI) reaching CTR of sub-50 ps full width at half maximum (FWHM) has been developed. However, a histogram of time differences between a pair of the CRIs shows undesirable side peaks, which are caused by gamma rays directly interacting with the micro channel plates (MCPs). Such direct interaction events are detrimental to the timing performance of the CRI. In this paper, we demonstrate an analytical method of deconvolving MCP direct interaction events from the timing histogram. Considering the information of the main and the two side peaks, the timing uncertainty caused by the MCP direct interaction events is deconvolved and the CTR of the CRI is analytically investigated. Consequently, the CTR is improved from 41.7 to 40.5 ps FWHM by the deconvolution. It means that a mixture of the Cherenkov radiator events and the MCP direct interaction events contribute to the CTR by a factor of 10 ps. The timing performance of the MCP direct interaction events are also evaluated. The CTR between the two MCPs is found to be 66.2 ps FWHM. This indicates that a photocathode-free radiation detector with high timing performance is possible. Elimination of the photocathode from the detector would make detector construction easier and more robust.

CAlcium fluoride for the study of Neutrinos and Dark matters by Low-energy Spectrometer (CANDLES) searches for neutrino-less double beta decay of $^{48}$Ca using a CaF$_2$ scintillator array. A high Q-value of $^{48}$Ca at 4,272 keV enabled us to achieve very low background condition, however, at the same it causes difficulties in calibrating the detector's Q-value region because of the absence of a standard high-energy $\gamma$-ray source. Therefore, we have developed a novel calibration system based on $\gamma$-ray emission by neutron capture on $^{28}$Si, $^{56}$Fe and $^{58}$Ni nuclei. In the paper, we report the development of the new calibration system as well as the results of energy calibration in CANDLES up to 9 MeV., Comment: 6 pages, 7 figures

The prefrontal cortex (PFC) is sensitive to the stress exposure and involved in stress coping. And the effects of gum chewing on the stress have been studied using NIRS. However, when measuring NIRS on PFC during gum chewing, blood flows in shallow tissues (scalp, skin, muscle) might be affected. A NIRS used in the present study first, which has a short distance (1 cm) and the usual (3 cm) source-detector (S-D) regression, can allow eliminating shallow tissues effect of gum chewing. The aim of this study was to investigate the hypothesis that gum chewing activates the right prefrontal cortex (PFC) in stress coping against negative sounds (NS) from the International Affective Digitized Sounds-2 (IADS) as a mental stress task. NS showed activation in the right PFC. There was a significant difference between NS, and NS with Gum, where NS with Gum showed an increased PFC activity, increased alpha wave appearance rate, a higher value in heart rate level, and a higher VAS score indicating 'pleasant'. Gum chewing activated right PFC activity while exposed to negative sounds from IADS as a mental stress task.

In a neutrinoless double-beta decay ($0\nu\beta\beta$) experiment, energy resolution is important to distinguish between $0\nu\beta\beta$ and background events. CAlcium fluoride for studies of Neutrino and Dark matters by Low Energy Spectrometer (CANDLES) discerns the $0\nu\beta\beta$ of $^{48}$Ca using a CaF$_2$ scintillator as the detector and source. Photomultiplier tubes (PMTs) collect scintillation photons. At the Q-value of $^{48}$Ca, the current energy resolution (2.6%) exceeds the ideal statistical fluctuation of the number of photoelectrons (1.6%). Because of CaF$_2$'s long decay constant of 1000 ns, a signal integration within 4000 ns is used to calculate the energy. The baseline fluctuation ($\sigma_{baseline}$) is accumulated in the signal integration, thus degrading the energy resolution. This paper studies $\sigma_{baseline}$ in the CANDLES detector, which severely degrades the resolution by 1% at the Q-value of $^{48}$Ca. To avoid $\sigma_{\rm baseline}$, photon counting can be used to obtain the number of photoelectrons in each PMT; however, a significant photoelectron signal overlapping probability in each PMT causes missing photoelectrons in counting and reduces the energy resolution. "Partial photon counting" reduces $\sigma_{baseline}$ and minimizes photoelectron loss. We obtain improved energy resolutions of 4.5-4.0% at 1460.8 keV ($\gamma$-ray of $^{40}$K), and 3.3-2.9% at 2614.5 keV ($\gamma$-ray of $^{208}$Tl). The energy resolution at the Q-value is estimated to be improved from 2.6% to 2.2%, and the detector sensitivity for the $0\nu\beta\beta$ half-life of $^{48}$Ca can be improved by 1.09 times., Comment: This manuscript is prepared for submission to IEEE Transaction on Nuclear Science. It contains 11 pages, 19 figures, and 1 table

High energy γ rays with several MeV produced by (n,γ) reactions can be a trouble for low background measurements in the underground laboratories such as double beta decay experiments. In the CANDLES project, which aimed to observe the neutrino-less double beta decay from 48Ca, γ rays caused by (n,γ) reactions were found to be the most significant background. The profile of the background was studied by measurements with a neutron source and a simulation with a validity check of neutron processes in Geant4. The observed spectrum of γ rays from (n,γ) reactions was well reproduced by the simulated spectra, which were originated from the surrounding rock and a detector tank made of stainless steel. The environmental neutron flux was derived by the observed event rate of γ rays from (n,γ) reactions using the simulation. The thermal and non-thermal neutron flux were found to be ( 1.3 ± 0.6 ) × 10 − 6 cm − 2 s − 1 and ( 1.1 ± 0.5 ) × 10 − 5 cm − 2 s − 1 , respectively. It is necessary to install an additional shield to reduce the background from (n,γ) reaction to the required level.

Background This study aimed to investigate the safety of sorafenib for the treatment of unresectable hepatocellular carcinoma in Chinese patients. Methods A subgroup of 345 Chinese patients from the international database of the Global Investigation of therapeutic DEcisions in hepatocellular carcinoma and Of its treatment with sorafeNib (GIDEON) study was included in this analysis. Safety assessment measures were adverse events (AEs) and serious adverse events (SAEs) graded using the National Cancer Institute Common Terminology Criteria version 3.0. Results Of 331 evaluable patients, 98% started sorafenib at 800 mg/day. The median treatment duration was 22 weeks (range, 0.1–116 weeks), and median overall survival (OS) was 322 days (10.7 months). Approximately 50% of patients had at least one adverse event, and 6% had grade 3–4 adverse events. Drug-related adverse events were experienced by 29% of patients, and 3.6% had grade 3–4 drug-related adverse events. Overall, 23% of patients (n = 77) experienced serious adverse events, among which only 1 event was drug-related (0.3%). No differences in overall adverse events, serious adverse events, and deaths were observed between Child-Pugh A and Child-Pugh B patients. The most frequent drug-related adverse events were dermatological/skin (24%), hand-foot skin reaction (20%), gastrointestinal (11%), and diarrhea (11%). The majority of adverse events occurred within 30 days of beginning sorafenib. Conclusion Sorafenib has satisfactory efficacy and safety in Chinese Child-Pugh A and B patients with unresectable HCC using the recommended dosage of 800 mg/day, and the safety of sorafenib is not affected by liver function. Prophylaxis for gastrointestinal adverse events may help to decrease dose interruptions or discontinuation. Trial registration ClinicalTrials.gov; Identifier: NCT00812175. Date of registration: December 19, 2008. Electronic supplementary material The online version of this article (10.1186/s12885-018-4144-9) contains supplementary material, which is available to authorized users.

The atomic-scale and nanoscale scratch wear resistance of a Cu47Zr45Al8 bulk metallic glass is studied in the present work using an atomic force microscopy focusing on the role of surface oxide and thermally induced changes in the glassy matrix. The wear rate is found to be significantly reduced and the wear resistance drastically improved by the formation of native and artificially grown surface oxides. This finding makes the studied alloy a very promising candidate for application as a wear resistant part in a micro-electro-mechanical device.

Background AJM300 (INN; carotegrast methyl), an orally active small molecule antagonist of the α4 subunit of α4β1/α4β7 integrins, demonstrated the efficacy and safety in patients with moderately active ulcerative colitis (UC) in a phase 2 study. The phase 3 study (NCT 03531892) of AJM300 as induction therapy was conducted in patients with moderately active UC. Methods Eligible patients were moderately active Japanese UC, defined as total Mayo Clinic scores (MCS) of 6–10, endoscopic subscores (ES) ≥2, and rectal bleeding subscores (RBS) ≥1, who had inadequate response or intolerance to oral 5-ASA. Followed by a 2-week single-blind placebo (PBO) run-in phase, patients were randomized 1:1 to receive AJM300 960 mg or PBO 3 times daily for 8 weeks. Responders or remitters were allowed to receive AJM300 960 mg again at the subsequent relapse (open-label). The primary endpoint was clinical response at week 8, defined as reduction of the MCS of ≥3-pts and ≥30%, reduction in RBS of ≥1-pt or RBS of ≤1, and ES ≤1. Results The randomized 203 patients had moderately active endoscopic evidence at baseline with median UC duration of 6.1 years and MCS of 7.8. For the primary endpoint, 45.1% (46/102) and 20.8% (21/101) of patients in the AJM300 and PBO groups, respectively, achieved clinical response at week 8 (OR=3.30 [95% CI, 1.73–6.29]; p=0.0003). Symptomatic remission, endoscopic improvement and endoscopic remission were also statistically significant for AJM300 vs PBO (Table). In case of episodic AJM300 treatment, AJM300 exhibited similar response to initial treatment. Overall, the incidence of AEs and serious AEs were similar between AJM300 and PBO. There were no deaths or cases of progressive multifocal leukoencephalopathy. Conclusion AJM300 induced clinical response as well as endoscopic remission with good tolerability. AJM300 may become a novel therapeutic option for patients who had inadequate response or intolerance to oral 5-ASA.

This article presents a method for precisely measuring the charge spread inside a silicon sensor, before it is sampled by the pixels of an X-ray imaging detector. The shape of the charge spread or pre-sampled point spread function (PSF) of the silicon sensor was demonstrated with a sub-micrometer resolution. The measurement setup comprises quasi-monochromatic X-ray beams emitted by a synchrotron radiation source, 5- μ m -diameter tungsten pinhole, sub- μ m -resolution X-ray beam profiler, and photodiode array in automation mode for step-scanning measurements. We obtained a value of 16.5–17.1 μ m (full width at half-maxima; sensor thickness: 650 μ m ; bias voltage: 750 V) based on preliminary experiments using 7.3 keV X-rays at BL19LXU of SPring-8. This value is consistent with the expected value obtained from the convolution of the beam profiles and pre-sampled PSFs corresponding to multiple photons for a dopant density of ∼ 1 0 12 cm − 3 within a range of approximately 1 μ m . We believe that our measurement method has sufficient potential for evaluating the pre-sampled PSF of a photodiode array with an accuracy of 1 μ m or less. The single-photon capability of imaging detectors depends on the detector noise as well as the pre-sampled PSF. Our measurement method, with high spatial resolution, is beneficial in the sense that it optimizes the pixel design of X-ray image sensors using a sample piece with a limited number of pixels.

The proposed Mitchell Institute Neutrino Experiment at Reactor (MINER) experiment at the Nuclear Science Center at Texas A&M University will search for coherent elastic neutrino-nucleus scattering within close proximity (about 2 m) of a 1 MW TRIGA nuclear reactor core using low threshold, cryogenic germanium and silicon detectors. Given the Standard Model cross section of the scattering process and the proposed experimental proximity to the reactor, as many as 5–20 events/kg/day are expected. We discuss the status of preliminary measurements to characterize the main backgrounds for the proposed experiment. Both in situ measurements at the experimental site and simulations using the MCNP and GEANT4 codes are described. A strategy for monitoring backgrounds during data taking is briefly discussed.

Background & Aim Aseptic processing is one of the most important issues in the production of cell-based products which are handled by opening the culture vessels. The practical level of aseptic processing depends on the design of aseptic environment where the equipment for research are installed in the cell manufacturing facility. An aseptic environment where biosafety cabinet (BSC) is installed as the aseptic processing area (Grade A) has vulnerability due to manual operations crossing between aseptic processing area and its surrounding area. Though robustness of an aseptic environment where isolator system is installed is much higher than that in the BSC, the facility cost of the isolator system may be more expensive. On the other hand, the facility with BSC has more lot out risks in production due to biological contamination, resulting in higher manufacturing cost. When the cost of goods for a cell-based product is calculated, it must be considered adding on the required resources with the failure probability of cell manufacturing caused by biological contamination. Methods, Results & Conclusion In this study, biological contamination risks depend on the design of aseptic environment construction has been assessed by introducing the method of work breakdown structure (WBS). Then the failure probability of cell manufacturing caused by biological contamination was simulated with consideration of the possibilities which is based on the particle contamination in the product depending on the equipment usage in facility. It is expected that the established assessment model will be useful for design of cell manufacturing facility.

The neutrino-less double beta decay (0νββ) is a powerful tool to probe the neutrino mass. The 0νββ is forbidden in Standard Model (SM) due to the violation of lepton number conservation. In experiments searching for 0νββ, the two-neutrino double beta decay (2νββ), which is an allowed process in SM, behaves as an irreducible background within the energy of interest. To discriminate the 0νββ from 2νββ, the energy resolution must be improved. The CANDLES experiment is searching for the 0νββ of 48Ca using CaF 2 (pure) scintillator as the detector and the source. Scintillation photons are collected by Photo Multiplier Tubes (PMTs) surrounding the crystals. A Flash Analog-to-Digital Converter records the waveform of each PMT. Because of the long decay time of CaF 2 (1 µsec), we make a signal integral of 4 µsec to calculate the obtained energy. Thus, the other fluctuation in the baseline is accumulated in the signal integration, and it makes the energy resolution worse. To reduce this fluctuation, we can count the number of photoelectrons in every PMT. Still, we have a significant overlapping probability of single photoelectron signals. This overlapping probability implies the photoelectrons lost, which causes terrible energy resolution. To improve the energy resolution, we introduce an alternative method named "partial photon counting" by dividing the waveform into two parts, then, perform signal integral in the prompt part and photon counting the second part. As a result, the energy resolution is reduced 4.0-3.5 % at 1460 keV (γ-ray of 40K) and 3-2.7 % at 2615 keV (γ-ray of 208Tl).

Background and aims Ultrasound-guided erector spinae block (ESPB) has recently been used for postoperative pain or chronic pain in abdominal area. In patients with spinal cord injury, the management of spasticity might improve patient’s discomfort and quality of life. After obtaining the written consent, we planned ultrasound-guided ESPB with phenol injection for abdominal spasticity, causing dyspnea. Methods The patient was a 34-year-old male with a spinal cord injury at C4. He was suffering from abdominal spasticity followed by light dyspnea. the patient was set in sitting position and the Th8-11 was obtained with ultrasound machine with 15 MHz linear type probe. a 25-gauge, 25-mm needle was inserted to the posterior side of transverse processes. the needle tip was directed to the plane deep to the erector spinae muscle and superficial to the transverse processes. In both site of Th8-11, 3 ml of 8% phenol was injected. Results No complications were observed through this procedure. Patient’s self-assessment 2 weeks after the block was that spasticity of the back muscle was reduced to one-third and dyspnea had improved. the positive effect of the block for spasticity lasted for more than 6 months. Conclusions Ultrasound guided ESPB with phenol for abdominal spasticity was effective for a period longer than expected. ESPB can be applied to the treatment for spasticity of spinal cord injury patients.

The aim of this study was to investigate the expression of tumour endothelial marker 8 (TEM8) in canine mammary gland tumours (MGTs) by immunohistochemistry and to evaluate the association between tumour cell TEM8 expression and tumour histological features, histological grades and expression of luminal and basal/myoepithelial cell markers. TEM8 expression was detected in60 % of neoplastic epithelial cells in all simple adenomas (n = 25), simple carcinomas (n = 43) and invasive micropapillary carcinomas (n = 5) studied. Six of the 18 solid carcinomas studied showed TEM8 expression in60% of carcinoma cells present in solid structures and in 12 of the 18 solid carcinomas,30% of the luminal structure-forming carcinoma cells showed TEM8 expression. TEM8 expression in the neoplastic cells was not associated with histological malignancy in canine MGTs. TEM8

Achieving direct imaging of the annihilation position of a positron on an event-by-event basis using an ultrafast detector would have a great impact on the field of nuclear medicine. Cherenkov emission is the most attractive physical phenomenon for realizing such an ultrafast timing performance. Moreover, a microchannel-plate photomultiplier tube (MCP-PMT) is one of the most promising photodetectors for fully exploiting the fast timing properties of Cherenkov emission owing to its excellent single photon time resolution of 25 ps full width at half maximum (FWHM). However, as the MCP structure generally contains a lead compound, the gamma rays frequently and directly interact with the MCP, resulting in the degradation of its timing performance and generation of undesirable side peaks in its coincidence timing histogram. To overcome this problem, we have developed a new MCP-PMT based on an MCP consisting of borosilicate glass, thus drastically reducing the probability of the photoelectric effect occurring in the MCP. To evaluate its insensitivity to gamma rays and its timing performance, a coincidence experiment was performed and showed that the probability of direct interactions was reduced by a factor of 3.4. Moreover, a coincidence time resolution of 35.4 ± 0.4 ps FWHM, which is equivalent to a position resolution of 5.31 mm, was obtained without any pulse height/area cut, improving to 28.7 ± 3.0 ps when selecting on the highest amplitude events by careful optimization of the voltage divider circuit of the new MCP-PMT. The timing performance of this new MCP-PMT presents an important step toward making direct imaging possible.

Metallic glasses are found to be applicable in micromechanical systems. When the size of the mechanical components is reduced to the micrometer and sub-micrometer level, the native surface oxide layer starts playing an important role in contact mechanical applications of metallic glasses. The nanoscale and atomic-scale scratch wear resistance of metallic glasses is studied in the present work using an atomic force microscopy at different loads. The wear rate is correlated with the properties of the metallic glasses studied and their respective surface oxides.

International audience; Purpose: To evaluate transarterial chemoembolization (TACE) use prior to and concomitantly with sorafenib in patients with unresectable hepatocellular carcinoma (HCC) across different global regions.Materials and Methods: GIDEON is an observational registry study of more than 3000 HCC patients. Patients with histologically, cytologically, or radiographically diagnosed HCC, and for whom a decision had been made to treat with sorafenib, were eligible. Patients were enrolled into the registry from 39 countries beginning in January 2009, with the last patient follow-up in April 2012. Detailed data on treatment history, treatment patterns, adverse events, and outcomes were collected. All treatment decisions were at the discretion of the treating physicians. Documented approval from local ethics committees was obtained, and all patients provided signed informed consent. Descriptive statistics, including minimum, median, and maximum, were calculated for metric data, and frequency tables for categorical data. Kaplan-Meier estimates with 95% confidence intervals were calculated for survival end points.Results: A total of 3202 patients were eligible for safety analysis, of whom 2631 (82.2%) were male. Median age was 62 years (range, 15-98 years). A total of 1511 (47.2%) patients underwent TACE prior to sorafenib; 325 (10.1%) underwent TACE concomitantly. TACE prior to sorafenib was more common in Japan and Asia- Pacific compared with all other regions (362 [71.3%] and 560 [60.3%] vs 12-209 [13.3%-37.1%]). Adverse events were reported in 2732 (85.3%) patients overall, with no notable differences in the incidence of adverse events, regardless of TACE treatment history. Overall survival was 12.7 months in prior-TACE patients, 9.2 months in non-prior-TACE patients, 21.6 months in concomitant-TACE patients, and 9.7 months in non-concomitant-TACE patients.Conclusion: Global variation exists in TACE use in sorafenib-treated HCC patients. The combination of TACE with sorafenib appears to be a well-tolerated and viable therapeutic approach.

We have studied the neutrino-less double beta decay(0νββ) of 48Ca with the CANDLES III system, which consists of CaF2(pure) scintillators. Rejection analyses for background events from radioactive contaminations in the CaF2(pure) scintillators were effective to reduce backgrounds in Qββ -value region. As the results, no events were observed in the region for the data of 131 days × 86 kg. It gave a lower limit 6.2 × 1022 year (90 % C.L.) for the half-life of 0νββ of 48Ca. For higher sensitive measurement of 48Ca 0νββ, we have developed new techniques for 48Ca enrichment and CaF2 scintillating bolometer. In this paper, we will also show current status of these techniques.

Background:Adult-onset Still’s disease (AOSD), a systemic inflammatory disorder, is characterized by high fever, evanescent rash, arthritis, and hyperferritinaemia. AOSD is also reported to be associated with other skin lesions, including persistent pruritic papules and plaques.Objectives:This study aimed to assess the significance of dyskeratotic skin lesions in Japanese AOSD patients.Methods:We retrospectively assessed the histology of persistent pruritic skin lesions and evanescent rashes and the relationship between dyskeratotic cells, serum markers, and outcomes in 20 Japanese AOSD patients, comparing AOSD histology with that of dermatomyositis (DM), drug eruptions, and graft-versus-host disease (GVHD).Results:Persistent pruritic lesions were characterized by scattered single keratinocytes with an apoptotic appearance confined to the upper layer of the epidermis and horny layer without inflammatory infiltrate. In contrast to AOSD, the histology of DM, drug eruption, and GVHD demonstrated dyskeratotic cells in all layers of the epidermis with inflammatory infiltrate. AOSD with evanescent rash showed no dyskeratotic cells. The dyskeratotic cells in pruritic AOSD lesions stained positive for ssDNA and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling, indicating apoptosis. Serum IL-18 was significantly higher in AOSD patients with dyskeratotic cells than those without, and generally required higher doses of glucocorticoids, immunosuppressants, and biologic agents. Two of ten AOSD patients with dyskeratotic cells died from haemophagocytic lymphohistiocytosis.Conclusion:Persistent pruritic AOSD skin lesions are characterized by dyskeratotic cells with apoptotic features, involving the upper layers of the epidermis. There may be a link to elevated IL-18. This dyskeratosis may be a negative prognostic indicator.Disclosure of Interests:None declared

The clinical superiority of proton therapy over photon therapy has recently gained recognition; however, the biological effects of proton therapy remain poorly understood. The lack of in vivo evidence is especially important. Therefore, the goal of this study was to validate the usefulness of Drosophila melanogaster as an alternative tool in proton radiobiology. To determine whether the comparative biological effects of protons and X rays are detectable in Drosophila, we assessed their influence on survival and mRNA expression. Postirradiation observation revealed that protons inhibited their development and reduced the overall survival rates more effectively than X rays. The relative biological effectiveness of the proton beams compared to the X rays estimated from the 50% lethal doses was 1.31. At 2 or 24 h postirradiation, mRNA expression analysis demonstrated that the expression patterns of several genes (such as DNA-repair-, apoptosis- and angiogenesis-related genes) followed different time courses depending on radiation type. Moreover, our trials suggested that the knockdown of individual genes by the GAL4/UAS system changes the radiosensitivity in a radiation type-specific manner. We confirmed this Drosophila model to be considerably useful to evaluate the findings from in vitro studies in an in vivo system. Furthermore, this model has a potential to elucidate more complex biological mechanisms underlying proton irradiation.

CANDLES(CAlcium fluoride for the study of Neutrinos and Dark matters by Low Energy Spectrometer) is the experiment to search for the neutrino-less double beta decay(0vββ) of 48Ca with CaF2 scintillator. 48Ca has the highest Q ββ -value (4.3 MeV) among all isotope candidates for 0vββ. It enables us to measure signals with very low background condition. After rejection analysis with 131 days × 86 kg data for background events from radioactive contaminations in the CaF2 scintillators, no events are observed in the Q ββ -value region. As a result, the half-life of 48Ca is greater than 6.2 × 1022 yr (90% confidence level). For further high sensitive measurement of 48Ca 0vββ search, we have been developing the 48Ca enrichment and CaF2 scintillating bolometer techniques. In this paper, the latest result for CANDLES and the status of scintillating bolometer development are described.

489 Background: Aberrant activation of fibroblast growth receptor (FGFR) signaling plays a role in UC. Rogaratinib, a pan-FGFR1-4 inhibitor, has promising efficacy and safety in pts with advanced muscle-invasive UC, selected based on FGFR1-3 mRNA overexpression and/or FGFR3-activating mutations/translocations. This Phase II/III, randomized, open-label study evaluated the efficacy of rogaratinib vs CT in pts with FGFR-positive advanced or metastatic UC who received prior platinum CT. We present an ORR analysis for rogaratinib vs CT. Methods: FGFR1/3 mRNA was tested by in situ hybridization of archival tissue. Pts were randomized 1:1 to 800 mg rogaratinib p.o. BID continuously or CT Q3W (i.v., docetaxel 75 mg/m2, paclitaxel 175 mg/m2, or vinflunine 320 mg/m2), and stratified by PIK3CA/ RAS-activating mutations, prior immunotherapy, and modified 4-factor Bellmunt risk score. Results: 87 pts were assigned to rogaratinib and 88 to CT. Overall, 82.9% were male, median age was 69.0 yrs (range: 36-89), 96.6% had stage IV disease, and 2.3% were stage IIIB. PIK3CA/ RAS-activating mutations were present in 11.4% of pts. ORRs of 19.5% and 19.3% (1-sided p=0.56) and disease control rates of 49.4% and 55.7% (p=0.84) were observed for rogaratinib and CT, respectively; median progression-free survival was 2.7 months (95% CI 1.6, 4.2) and 2.9 months (95% CI 2.6, 4.2). Grade 3-4 treatment-emergent adverse events occurred in 40/86 pts (47%) treated with rogaratinib and 46/82 pts (56%) with CT, most commonly anemia (3% vs 15%), neutropenia (1% vs 17%), asthenia (9% vs 1%), lipase increase (8% vs 2%), fatigue (2% vs 6%), and urinary tract infection (2% vs 6%). Exploratory analysis of pts with FGFR3 DNA alterations (4 spot mutations and fusions) showed ORRs of 52.4% with rogaratinib and 26.7% with CT. Conclusions: In pts with FGFR1/3 tumor mRNA-positive UC, rogaratinib had efficacy comparable with standard CT and an acceptable safety profile. Subgroup analysis suggests rogaratinib may be more active in pts with an FGFR3 DNA alteration. Sensitivity analysis of biomarker subgroups is ongoing. Clinical trial information: NCT03410693.

564 Background: REG is a multikinase inhibitor with immunomodulatory activity and PEMBRO is an anti-PD-1 monoclonal antibody. Both are approved as monotherapy for patients (pts) with HCC previously treated with sorafenib. Based on their potential synergistic effects, we conducted a phase 1b study of REG plus PEMBRO for first-line treatment of advanced HCC. Methods: This is an ongoing, open-label, dose-escalation study in pts with advanced HCC who had no prior systemic therapy. In the first cohort, pts received REG 120 mg/day PO for 3 weeks on/1 week off plus PEMBRO 200 mg IV q 3 weeks. In later cohorts, the REG dose could be escalated (160 mg) or reduced (80 mg) based on the modified toxicity probability interval design; the PEMBRO dose is fixed. The primary objective is safety and tolerability. Secondary objectives are to define the maximum tolerated dose (MTD) and recommended phase 2 dose, and to assess antitumor activity. Results: As of August 23, 2019, 29 pts have been treated at the REG 120 mg level. Median age is 65 years (range 32–81); 41%/55% of pts are BCLC stage B/C; 100% are Child–Pugh A; ECOG status 0/1 is 72%/28%. Dose-limiting toxicities occurred in 4/18 evaluable pts: grade (Gr) 3 increased ALT/AST with Gr 2 increased bilirubin (n = 2); Gr 3 rash (n = 2). The MTD of REG in the combination was 120 mg. Most common Gr 3 or 4 treatment-emergent adverse events (TEAEs) are shown (n = 29). There were no Gr 5 TEAEs. 59%/31% of pts had REG/PEMRO-related Gr 3 or 4 TEAEs. Dose modifications (reductions or interruptions) of REG/PEMBRO for drug-related TEAEs occurred in 59%/31% of pts. Of 23 evaluable pts, 7 (30%) had a partial response (PR) and 14 (61%) had stable disease (RECIST v1.1); 1 additional pt had PR by mRECIST. Conclusions: The combination of REG plus PEMBRO for first-line treatment of advanced HCC showed no unexpected safety signals and encouraging antitumor activity. Accrual is continuing at REG 120 mg dose and an expansion cohort evaluating REG 80 mg plus PEMBRO is planned. Clinical trial information: NCT03347292. [Table: see text]

We have studied the neutrino-less double beta decay(0νββ) of 48Ca by using CaF2(pure) scintillators. Analysis for rejection of backgrounds(212Bi→ 212Po events and 208Tl events) was effective to reduce backgrounds in Qββ-value region. No events are observed in the Qββ-value region for the data of 131 days × 86 kg. It gives a lower limit (90% confidence level) of (math) > 6.2 × 1022 year (preliminary) for the half-life of 0νββ of 48Ca.

Sodium tetraphenylborate (NaBPh 4 ) induces the highly ordered structures, such as multi-lamellar vesicles, in the water/3-methylpridine mixture. In this sense, NaBPh 4 can behave as a surfactant in the organic solvent mixtures. It is then expected that NaBPh 4 also behaves as a surfactant in neat water. To examine this assumption, the effects of NaBPh 4 on the surface structure and the bulk structure of the water were measured. It was shown that the surface tension of water decreases by dissolving NaBPh 4 . Additionally, micelle-like structure was confirmed in the water/NaBPh 4 mixtures.