Development of Quantitative Chemical Ionization Using Gas Chromatography/Mass Spectrometry and Gas Chromatography/Tandem Mass Spectrometry for Ambient Nitro- and Oxy-PAHs and Its Applications.

The concentration of polycyclic aromatic hydrocarbons (PAHs) in the atmosphere has been continually monitored since their toxicity became known, whereas nitro-PAHs (NPAHs) and oxy-PAHs (OPAHs), which are derivatives of PAHs by primary emissions or secondary formations in the atmosphere, have gained attention more recently. In this study, a method for the quantification of 18 NPAH and OPAH congeners in the atmosphere based on combined applications of gas chromatography coupled with chemical ionization mass spectrometry is presented. A high sensitivity and selectivity for the quantification of individual NPAH and OPAH congeners without sample preparations from the extract of aerosol samples were achieved using negative chemical ionization (NCI/MS) or positive chemical ionization tandem mass spectrometry (PCI-MS/MS). This analytical method was validated and applied to the aerosol samples collected from three regions in Northeast Asia-namely, Noto, Seoul, and Ulaanbaatar-from 15 December 2020 to 17 January 2021. The ranges of the method detection limits (MDLs) of the NPAHs and OPAHs for the analytical method were from 0.272 to 3.494 pg/m3 and 0.977 to 13.345 pg/m3, respectively. Among the three regions, Ulaanbaatar had the highest total mean concentration of NPAHs and OPAHs at 313.803 ± 176.349 ng/m3. The contribution of individual NPAHs and OPAHs in the total concentration differed according to the regional emission characteristics. As a result of the aerosol samples when the developed method was applied, the concentrations of NPAHs and OPAHs were quantified in the ranges of 0.016~3.659 ng/m3 and 0.002~201.704 ng/m3, respectively. It was concluded that the method could be utilized for the quantification of NPAHs and OPAHs over a wide concentration range.

Pharmacological Inhibition of Caspase-1 Ameliorates Cisplatin-Induced Nephrotoxicity through Suppression of Apoptosis, Oxidative Stress, and Inflammation in Mice.

Caspase-1 is a proinflammatory caspase responsible for the proteolytic conversion of the precursor forms of interleukin-1ß to its active form and plays an important role in the pathogenesis of various inflammatory diseases. It was reported that genetic deficiency of caspase-1 prevented cisplatin-induced nephrotoxicity. However, whether pharmacological inhibition of caspase-1 also has a preventive effect against cisplatin-induced kidney injury has not been evaluated. In this study, we examined the effect of Ac-YVAD-cmk, a potent caspase-1-specific inhibitor, on renal function and histology in cisplatin-treated mice and explored its underlying mechanisms. We found that administration of Ac-YVAD-cmk effectively attenuated cisplatin-induced renal dysfunction, as evidenced by reduced plasma levels of blood urea nitrogen and creatinine, and histological abnormalities, such as tubular cell death, dilatation, and cast formation. Administration of Ac-YVAD-cmk inhibited caspase-3 activation as well as caspase-1 activation and attenuated apoptotic cell death, as assessed by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling, in the kidneys of cisplatin-treated mice. Cisplatin-induced G2/M arrest of renal tubular cells was also reduced by caspase-1 inhibition. In addition, administration of Ac-YVAD-cmk reversed increased oxidative stress and depleted antioxidant capacity after cisplatin treatment. Moreover, increased macrophage accumulation and elevated expression of cytokines and chemokines were attenuated by caspase-1 inhibition. Taken together, these results suggest that caspase-1 inhibition by Ac-YVAD-cmk protects against cisplatin-induced nephrotoxicity through inhibition of renal tubular cell apoptosis, oxidative stress, and inflammatory responses. Our findings support the idea that caspase-1 may be a promising pharmacological target for the prevention of cisplatin-induced kidney injury.

Does Bladder Cancer Subtype Influence Pathologic Complete Response (pCR) and Pelvic Diffusion-Weighted Magnetic Resonance Imaging (DW-MRI) Response Evaluation After Neoadjuvant Chemotherapy? Pathological Perspective.

INTRODUCTION: We aimed to provide a pathological perspective on the management of muscle-invasive bladder cancer (MIBC) by correlating the prechemotherapy transurethral resection of bladder tumor findings and postchemotherapy radiologic evaluation with final radical cystectomy (RC) findings. MATERIALS AND METHODS: This retrospective study included 79 MIBC patients treated with neoadjuvant chemotherapy (NAC) and RC. Pelvic diffusion-weighted magnetic resonance imaging (DW-MRI) and pathologic reports were retrieved from our institutional database. All pathology slides were reviewed based on diagnostic criteria with high interobserver reproducibility. RESULTS: Pathologic complete response (pCR) was confirmed in 32 patients (40.5%). The concordance and discordance between MRI and RC findings occurred in 68.3% and 31.7% of cases, respectively. The 21.5% of cases that were clinical CR (cCR) on MRI actually achieved pCR on RC specimens and 46.8% of cases that were non-cCR on MRI were actually non-pCR on RC specimens. In 19.0% of cases, RC findings were pCR, but MRI demonstrated residual tumor and the opposite was 12.7%. The greatest discrepancy between the 2 methods (75%, 3/4) was for the plasmacytoid subtype. Plasmacytoid histology was the most common histological subtype identified in RC specimens after NAC, followed by micropapillary and squamous histologies. CONCLUSIONS: We found that all cases with plasmacytoid and micropapillary subtypes, and squamous differentiation did not show pCR. In particular, the largest discrepancy between MRI findings and RC pathology after NAC was seen in the plasmacytoid subtype. An accurate pathologic diagnosis based on strict criteria to identify histological subtypes of MIBC is necessary for proper treatment.

Statistical comparison for assessing agreement between two mass spectrometric methods for the analysis of polychlorinated dibenzo-p-dioxins and furans (PCDDs/Fs) in contaminated soils.

A gas chromatography coupled to high-resolution mass spectrometry (GC-HR/MS) has been used as the standard method for the quantification of polychlorinated dibenzo-p-dioxins and furans (PCDDs/Fs), which are regulated at screening and action levels in the environment. However, several alternative methods have been attempted due to the disadvantage of its high cost. Although a gas chromatography with triple quadrupole mass spectrometry (GC-QqQ-MS/MS) has been used in a wide variety of sample matrices, showing that they are interchangeable, there has been a lack of comprehensive studies on statistical agreement with GC-HR/MS. In this study, a pairwise comparison of the total concentrations of PCDDs/Fs in 90 soil field samples obtained by two mass spectrometric methods was performed using the Passing-Bablok (P&B) regression and Bland-Altman (B&A) analysis for the method comparison. According to the result of the B&A analysis, the concentration range of PCDDs/Fs was between 98.2 and 1760 pg/g showed good agreement between two methods at the 95 % confidence level (CL). Although there was a large discrepancy between the two methods in the low concentrations (<16.5 pg/g of PCDDs/Fs), this result was similar to the P&B regression analysis. As the verification results by B&A and P&B regression analysis, the interchangeable concentration range between the two methods was confirmed to be adequate for the monitoring of PCDDs/Fs regulating levels in soils.

A scintillating-fiber detector for making high-time-resolution secondary D-T neutron measurements in KSTAR.

A scintillating fiber (Sci-Fi) detector for the middle neutron flux range was installed in KSTAR as part of a collaboration between the National Institute for Fusion Science and the Korea Institute of Fusion Energy. The detector could make relatively high-time-resolution measurements of secondary deuterium (D)-tritium (T) neutron fluxes to investigate the degradation of D-D-born triton confinement, which is crucial for demonstrating alpha particle confinement, particularly above 0.9 MA in KSTAR. The pulse-height spectrum of the Sci-Fi detector exhibited two peaks, the higher of which corresponded to D-T neutrons. A discrimination technique was applied to extract the D-T neutron signal, revealing the time evolution of the D-T neutron flux during relatively high plasma current discharges with a 50 ms temporal resolution. Future research will involve investigating the causes of the degradation of the triton burnup ratio above 0.9 MA in KSTAR.

Four versus six cycles of platinum-based chemotherapy for advanced Urothelial carcinoma in the era of immune checkpoint inhibitors: A retrospective cohort study (FOCUS, KCSG-GU23-08).

INTRODUCTION: This study aimed to assess the survival outcomes of four versus six cycles of first-line platinum-based chemotherapy (PBCT) in the era of immune checkpoint inhibitor (ICI) for patients with advanced urothelial carcinoma (UC). PATIENTS AND METHODS: Patients with histologically confirmed advanced UC were allocated to either the 4-cycle PBCT (C4) or 6-cycle PBCT (C6) groups and retrospectively analyzed. After the planned cycles, active surveillance was conducted every 6-8 weeks, followed by second-line treatments, including ICIs, upon progression. The primary endpoint was overall survival (OS). RESULTS: Of the 161 patients initiated with PBCT between September 2016 and February 2023, 27 were deemed ineligible, leaving 134 patients for analysis (C4, n = 58; C6, n = 77). Baseline characteristics, including cisplatin eligibility, were similar between the groups. With a median follow-up of 23.7 months (95 % confidence interval (CI), 20.3-27.1), no significant difference was observed in OS between the C6 and C4 groups (18.7 months vs. 17.0 months; hazard ratio (HR) 1.27, P = 0.343). In multivariate analysis adjusted for sex, initial presentation, metastatic lesion, and ECOG PS, no significant difference was observed between the C6 and C4 groups (HR 1.29, 95 % CI, 0.78-2.14, P = 0.315). CONCLUSIONS: This study showed that four cycles of PBCT do not differ from six cycles regarding OS.

Developing an Improved Strategy for the Analysis of Polychlorinated Dibenzo-p-Dioxins/Furans and Dioxin-like Polychlorinated Biphenyls in Contaminated Soils Using a Combination of a One-Step Cleanup Method and Gas Chromatography with Triple Quadrupole Mass Spectrometry.

Soils contaminated with polychlorodibenzo-p-dioxins (PCDDs), polychlorodibenzofurans (PCDFs), and dioxin-like (dl) polychlorinated biphenyls (PCBs), known as persistent organic pollutants (POPs), have garnered global attention because of their toxicity and persistence in the environment. The standard method for target analytes has been used; however, it is an obstacle in large-scale sample analysis due to the comprehensive sample preparation and high-cost instrumental analysis. Thus, analytical development of inexpensive methods with lower barriers to determine PCDDs/Fs and dl-PCBs in soil is needed. In this study, a one-step cleanup method was developed and validated by combining a multilayer silica gel column and Florisil micro-column followed by gas chromatography with triple quadrupole mass spectrometry (GC-QqQ-MS/MS). To optimize the separation and quantification of 17 PCDDs/Fs and 12 dl-PCBs in soils, the sample cleanup and instrumental conditions were investigated. For quantification method validation, spiking experiments were conducted to determine the linearity of the calibration, recovery, and method detection limit of PCDDs/Fs and dl-PCBs using isotopic dilution GC-QqQ-MS/MS. The applicability of the simultaneous determination of PCDDs/Fs and dl-PCBs was confirmed by the recovery of native target congeners and labeled surrogate congeners spiked into the quality-control and actual soil samples. The results were in good agreement with the requirements imposed by standard methods. The findings in this work demonstrated the high accessibility of the sample cleanup and analysis methods for the efficient determination of PCDDs/Fs and dl-PCBs in contaminated soils.

Protective Effects of Orexin A in a Murine Model of Cisplatin-Induced Acute Kidney Injury.

Cisplatin is a chemotherapeutic agent widely used in the treatment of various cancers, but its application is often limited due to complications such as acute kidney injury (AKI). Orexins are hypothalamic neuropeptides that modulate the sleep-wake cycle, neuroendocrine function, and the autonomic nervous system. Emerging evidence suggests that orexin A (OXA) has anti-inflammatory and neuroprotective effects in animal models of neuroinflammatory diseases of the central nervous system. However, the effect of OXA on kidney diseases has not been examined. Here, we investigated whether OXA has a protective effect in a murine model of cisplatin-induced AKI. Intraperitoneal administration of OXA ameliorated renal dysfunction, and histological abnormalities in mice injected with cisplatin. OXA inhibited cisplatin-induced oxidative stress through the modulation of prooxidant and antioxidant enzymes. This peptide reduced apoptotic cell death by inhibiting the p53-mediated pathway in mice injected with cisplatin. OXA also alleviated cisplatin-induced cytokine production and macrophage infiltration into injured kidneys. Taken together, these results showed that OXA ameliorates cisplatin-induced AKI via antioxidant, anti-apoptotic, and anti-inflammatory actions. This peptide could be a potential therapeutic agent for cisplatin-induced AKI.

ß­catenin blockers enhance the effect of CDK4/6 inhibitors on stemness and proliferation suppression in endocrine­resistant breast cancer cells.

Wnt/ß­catenin signaling is involved in endocrine resistance and stem cell­like properties of hormone receptor­positive breast cancer cells. Palbociclib is a well­known inhibitor of cyclin­dependent kinase 4 and 6 (CDK4/6 inhibitor) that downregulates the activation of retinoblastoma protein, thereby inhibiting the cell cycle in breast cancer cells. The inhibitory effects of a combination of palbociclib and ICG­001, a ß­catenin small­molecule inhibitor, were investigated in tamoxifen­resistant breast cancer cell lines. Tamoxifen­resistant MCF­7 (TamR) cells were established by continuously exposing MCF­7 cells to tamoxifen. The characteristics associated with the stem cell­like property of cancer were assessed using western blotting, cell cycle analysis, and the mammosphere assay. The effects of the combination of palbociclib and ICG­001 were evaluated in control MCF­7 and TamR cell lines. Compared with control cells, TamR cells exhibited elevated levels of Nanog, Sox2, ALDH1, and p­STAT3, indicating stem cell­like characteristics, and elevated ß­catenin activity. TamR cells also showed significantly higher mammosphere­forming efficiency. Several markers of stem cell­like nature of TamR cells showed reduced levels upon treatment of cells with the drug combination; there was a greater reduction in the levels of these markers when the cells were treated with the combination than in the case where cells were treated with one of the drugs individually (combination index value for 25 µM palbociclib and 50 µM ICG­001 was 1.1±0.02). TamR cells treated with the palbociclib and ICG­001 combination demonstrated significantly reduced cell proliferation and mammosphere­forming efficiency compared with the cells treated with one of these drugs. The combination of the drugs could additively inhibit proliferation and suppress stem cell­like characteristics. These results suggest that ß­catenin plays a role in endocrine­resistant breast cancer; the inhibition of ß­catenin and CDK4/6 together can overcome endocrine resistance in breast cancer cells.

Gas chromatography-triple quadrupole mass spectrometry as a cost-effective method for the determination of polychlorinated dibenzo-p-dioxins and furans in contaminated soils.

The aim of this study was to evaluate the performance of gas chromatography (GC)-triple quadrupole mass spectrometry (QqQ, MS/MS) as an alternative to the standard GC-high resolution mass spectrometry (GC-HR/MS) for soils contaminated with polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs). GC-QqQ (MS/MS) using a dynamic multiple reaction monitoring (dMRM) mode was optimized for the quantitative analysis of 17 PCDD/Fs. A comparative study between GC-QqQ (MS/MS) and GC-HR/MS was carried out to validate the results of actual field soil samples. Although GC-HR/MS has excellent sensitivity and selectivity, the validation parameters obtained by GC-QqQ (MS/MS) also met the recommended criteria of the standard method. The results for total and I-TEQ (international toxic equivalent) value of the PCDD/F concentrations of over 86.0 pg/g and 4.3 pg I-TEQ/g, respectively, in actual field soil samples showed good agreement between the two methods, falling within ±25% relative difference. In consideration of the remediation goal (100 pg I-TEQ/g), GC-QqQ (MS/MS) can be an alternative cost-effective method for use in soil remediation research.

Limited role of interim PET/CT in patients with diffuse large B-cell lymphoma treated with R-CHOP.

Positron emission tomography (PET) has been found useful in monitoring response to treatment of malignant lymphoma. We investigated the ability of interim PET to monitor response to standard dose R-CHOP chemotherapy in chemotherapy-naïve patients with diffuse large B-cell lymphoma (DLBCL). Between March 2004 and April 2009, 155 DLBCL patients treated with R-CHOP and available for interim and post-treatment PET/CT were identified and included in this analysis. Response, progression-free survival (PFS), and overall survival (OS) were compared between interim PET/CT-negative and positive group, and among three patient groups which were categorized based on their interim and post-treatment PET/CT: those with early metabolic complete response (mCR), delayed mCR, and never mCR. Interim PET/CT-negative patients (n=100) showed superior CR rates to interim PET/CT-positive patients (n=55; 93% vs 62%, P<0.001). However, there was no difference in PFS (P=0.07) and OS (P=0.24) between interim PET/CT-negative and positive group. We categorized patients into three groups, with 100 (64%) in the early mCR group, 35 (23%) in the delayed mCR group, and 20 (13%) in the never mCR group. Early mCR and delayed mCR group did not differ significantly in PFS (P=0.84) or OS (P=0.20). However, the survival outcome in the never mCR group was significantly inferior to the combined early and delayed mCR group. The result from this study suggests that interim PET/CT might be an inappropriate tool for designing risk-adaptive therapy in chemotherapy-naïve DLBCL patients treated with R-CHOP. Prospective trials should be performed to clearly determine the role of interim PET/CT.

Kahweol Ameliorates Cisplatin-Induced Acute Kidney Injury through Pleiotropic Effects in Mice.

Cisplatin is an effective chemotherapeutic agent, but its clinical use is frequently limited by its nephrotoxicity. The pathogenesis of cisplatin-induced acute kidney injury (AKI) remains incompletely understood, but oxidative stress, tubular cell death, and inflammation are considered important contributors to cisplatin-induced renal injury. Kahweol is a natural diterpene extracted from coffee beans and has been shown to possess anti-oxidative and anti-inflammatory properties. However, its role in cisplatin-induced nephrotoxicity remains undetermined. Therefore, we investigated whether kahweol exerts a protective effect against cisplatin-induced renal injury. Additionally, its mechanisms were also examined. Administration of kahweol attenuated renal dysfunction and histopathological damage together with inhibition of oxidative stress in cisplatin-injected mice. Increased expression of nicotinamide adenine dinucleotide phosphate oxidase 4 and decreased expression of manganese superoxide dismutase and catalase after cisplatin treatment were significantly reversed by kahweol. Moreover, kahweol inhibited cisplatin-induced apoptosis and necroptosis in the kidneys. Finally, kahweol reduced inflammatory cytokine production and immune cell accumulation together with suppression of nuclear factor kappa-B pathway and downregulation of vascular adhesion molecules. Together, these results suggest that kahweol ameliorates cisplatin-induced renal injury via its pleiotropic effects and might be a potential preventive option against cisplatin-induced nephrotoxicity.

Inhibition of p300 by Garcinol Protects against Cisplatin-Induced Acute Kidney Injury through Suppression of Oxidative Stress, Inflammation, and Tubular Cell Death in Mice.

Emerging evidence suggests that epigenetic mechanisms such as histone modification are crucially involved in the pathophysiology of acute kidney injury (AKI). The histone acetyltransferase p300 regulates several biological processes through the acetylation of histones or transcription factors. However, the role of p300 in cisplatin-induced AKI remains poorly understood. Therefore, we investigated the effects of garcinol, a potent p300 inhibitor, on cisplatin-induced AKI and explored the mechanisms. Administration of garcinol significantly reversed the upregulation of p300 and increased acetylation of histone H3, along with amelioration of renal dysfunction and histopathological injury in the kidneys of cisplatin-injected mice. Garcinol also attenuated oxidative stress and reduced expression of pro-oxidant enzymes. In addition, garcinol reduced the elevated production of cytokines and chemokines and suppressed immune cell accumulation together with downregulation of vascular adhesion molecules. These beneficial effects of garcinol were associated with a reduction in acetylation of the p65 subunit of nuclear factor kappa-B. Further, garcinol significantly inhibited apoptosis and caspase-3 activation, with a decrease in p53 acetylation in cisplatin-injected mice. Taken together, we demonstrated that the inhibition of p300 by garcinol ameliorated cisplatin-induced renal injury, presumably through epigenetic mechanisms. These results suggest that garcinol might be a potential preventive agent for cisplatin-induced AKI.

Melatonin Attenuates Cisplatin-Induced Acute Kidney Injury through Dual Suppression of Apoptosis and Necroptosis.

Melatonin is well known to modulate the sleep-wake cycle. Accumulating evidence suggests that melatonin also has favorable effects such as anti-oxidant and anti-inflammatory properties in numerous disease models. It has been reported that melatonin has therapeutic effects against cisplatin-induced acute kidney injury (AKI). However, mechanisms underlying the therapeutic action of melatonin on the renal side-effects of cisplatin therapy remain poorly understood. In this study, we showed that melatonin treatment significantly ameliorates cisplatin-induced acute renal failure and histopathological alterations. Increased expression of tubular injury markers was largely reduced by melatonin. Melatonin treatment inhibited caspase-3 activation and apoptotic cell death. Moreover, protein levels of key components of the molecular machinery for necroptosis were decreased by melatonin. Melatonin also attenuated nuclear factor-κB activation and suppressed expression of pro-inflammatory cytokines. Consistent with in vivo findings, melatonin dose-dependently decreased apoptosis and necroptosis in cisplatin-treated mouse renal tubular epithelial cells. Collectively, our findings suggest that melatonin ameliorates cisplatin-induced acute renal failure and structural damages through dual suppression of apoptosis and necroptosis. These results reveal a novel mechanism underlying the therapeutic effect of melatonin against cisplatin-induced AKI and strengthen the idea that melatonin might be a promising therapeutic agent for the renal side-effects of cisplatin therapy.

Pharmacological Activation of Sirt1 Ameliorates Cisplatin-Induced Acute Kidney Injury by Suppressing Apoptosis, Oxidative Stress, and Inflammation in Mice.

Sirtuin 1 (Sirt1) is an essential modulator of cellular metabolism and has pleiotropic effects. It was recently reported that Sirt1 overexpression in kidney tubule ameliorates cisplatin-induced acute kidney injury (AKI). However, whether pharmacological activation of Sirt1 also has a beneficial effect against the disease remains unclear. In this study, we aimed to evaluate whether SRT1720, a potent and specific activator of Sirt1, could ameliorate cisplatin-induced AKI. We found that SRT1720 treatment ameliorated cisplatin-induced acute renal failure and histopathological alterations. Increased levels of tubular injury markers in kidneys were significantly attenuated by SRT1720. SRT1720 treatment also suppressed caspase-3 activation and apoptotic cell death. Increased expression of 4-hydroxynonenal, elevated malondialdehyde level, and decreased ratio of reduced glutathione/oxidized glutathione after cisplatin injection were significantly reversed by SRT1720. In addition, SRT1720 treatment decreased renal expression of pro-inflammatory cytokines and prevented macrophage infiltration into damaged kidneys. We also showed that the therapeutic effects of SRT1720 were associated with reduced acetylation of p53 and nuclear factor kappa-B p65 and preservation of peroxisome function, as evidenced by recovered expression of markers for number and function of peroxisome. These results suggest that Sirt1 activation by SRT1720 would be a useful therapeutic option for cisplatin-induced AKI.

High detection efficiency scintillating fiber detector for time-resolved measurement of triton burnup 14 MeV neutron in deuterium plasma experiment.

The behavior of the 1 MeV triton has been studied in order to understand the alpha particle confinement property in the deuterium operation of toroidal fusion devices. To obtain time evolution of the deuterium-tritium (D-T) neutron emission rate where the secondary DT neutron emission rate is approximately 1012 n/s, we designed two high detection efficiency scintillating fiber (Sci-Fi) detectors: a 1 mm-diameter scintillation fiber-based detector Sci-Fi1 and a 2 mm-diameter scintillation fiber-based detector Sci-Fi2. The test in an accelerator-based neutron generator was performed. The result shows that the directionality of each detector is 15° and 25°, respectively. It is found that detection efficiency for DT neutrons is around 0.23 counts/n cm2 for the Sci-Fi1 detector and is around 1.0 counts/n cm2 for the Sci-Fi2 detector.

Initial operation results of NE213 scintillation detector for time-resolved measurements on triton burnup in KSTAR.

In time-resolved measurement for triton burnup in Korea Superconducting Tokamak Advanced Research (KSTAR) deuterium plasmas, an NE213 liquid scintillation detector was installed and operated during the 2017 KSTAR campaign. The detector is composed of an NE213 scintillator (50 mm in diameter and 10 mm in thickness) and a photomultiplier tube (PMT). The PMT anode signal was processed under a data acquisition system which contains a field programmable gate array circuit and pulse processing software that is capable of discriminating gamma-ray and neutron pulse signals. In order to determine an appropriate threshold level for the 14 MeV neutron signal resulting from triton burnup, the NE213 scintillation detector was calibrated by using d-d and d-t neutron generators at the National Fusion Research Institute and Intense 14 MeV Neutron Source Facility, OKTAVIAN, Osaka University, Japan. The detector was installed on KSTAR with a 10 mm thick soft-iron stray magnetic field shield and a radiation shield which consists of 100 mm thick lead blocks and 200 mm thick borated polyethylene blocks. A discrimination range for d-t neutron was determined based on test results from neutron generators and KSTAR. Data points selected from the discrimination range were consistent with the classical triton confinement characteristics. In conclusion, under condition of an input counting rate of 1.9 × 105 counts per second (CPS), the detector is able to measure triton burnup signals up to 500 CPS for various plasma parameters.

Characterization of photo-multiplier tube as ex-vessel radiation detector in tokamak.

Feasibility of using conventional photo-multiplier tubes (PMTs) without a scintillator as an ex-vessel radiation detector in a tokamak environment is studied. Basic irradiation tests using standard gamma ray sources and a d-d neutron generator showed that the PMT is responding both to gamma photons and neutrons, possibly due to the direct generation of secondary electrons inside the PMT by the impingement of high energy photons. Because of the selective sensitivity of the PMT to hard x-ray and neutrons in ohmic and neutral beam injected plasmas, respectively, it is shown that the PMT with certain configuration can be utilized either to monitor the fluctuation in the fusion neutron generation rate or to study the behavior of runaway electrons in tokamaks.

Clinical significance of systemic chemotherapy after curative resection of metachronous pulmonary metastases from colorectal cancer.

PURPOSE: The use of systemic chemotherapy after resection remains controversial in patients with resectable metachronous pulmonary metastases from colorectal cancer (CRC). This retrospective study compared systemic chemotherapy with observation alone after resection of pulmonary metastases from CRC. METHODS: Between 2001 and 2015, 91 patients with metachronous pulmonary metastases underwent curative surgical resection at five centers. Patients with stage IV at diagnosis were excluded. Overall survival (OS) was defined as the time from pulmonary resection until death. The disease-free interval (DFI) was defined as the time from pulmonary resection until recurrence or death. RESULTS: Among the 91 patients, 63 were in the chemotherapy group, while 28 were in the observation alone group. The characteristics were similar between the two groups, except for the carcinoembryonic antigen level after pulmonary metastases and the use of adjuvant treatment after resection of the primary tumor. With a median follow-up duration of 46 months (11-126), the estimated 5-year DFI and OS rates were 32.8 and 61.4%, respectively. The chemotherapy following pulmonary resection was not significantly associated with the DFI (p = 0.416) and OS (p = 0.119). CONCLUSION: Systemic chemotherapy after pulmonary resection was not found to have a significant effect on survival.

Coordinated underground measurements of gamma-ray emitting radionuclides for plasma physics research.

Forty-eight samples made of CaF2, LiF and YVO4 were placed inside the KSTAR Tokamak and irradiated by neutrons and charged particles from eight plasma pulses. The aim was to provide information for plasma diagnostics. Due to the short pulse durations, the activities induced in the samples were low and therefore measurements were performed in five low-background underground laboratories. Details of the underground measurements, together with data on the quality control amongst the radiometric laboratories, are presented.