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The protective effect of magnesium (Mg) supplementation against cisplatin (CDDP)-induced nephrotoxicity has been widely described; however, the optimal dose of Mg supplementation is unclear. The aim of this study was to investigate whether 20 mEq of Mg supplementation is more effective than 8 mEq Mg in preventing CDDP-induced nephrotoxicity, as well as the associated risk factors, in cancer patients treated with CDDP-based chemotherapy.Pooled data of 272 patients receiving 20 mEq or 8 mEq Mg supplementation to CDDP-based chemotherapy from a multicenter, retrospective, observational study were compared using propensity score matching. Separate multivariate logistic regression analyses were used to identify the risk factors for renal failure induced by each treatment dose.There was no significant difference in the incidence of nephrotoxicity between the 8 mEq and 20 mEq groups (P = 0.926). There was also no significant difference in the severity of nephrotoxicity, elevated serum creatinine levels, and decreased estimated creatinine clearance levels between the two groups. Cardiac disease and albumin levels were identified as independent risk factors for CDDP-induced nephrotoxicity.We did not find an advantage of 20 mEq over 8 mEq Mg supplementation in terms of a preventive effect against CDDP-induced nephrotoxicity. The optimal dose of Mg supplementation for the prevention of CDDP-induced nephrotoxicity remains unknown, and further studies are warranted.

Chemotherapy for multiple primary malignancies is challenging. We herein report a case of synchronous primary lung adenocarcinoma and hepatocellular carcinoma (HCC). A 72-year-old man was admitted for the evaluation of an abnormal shadow on his lung. Computed tomography revealed a lung nodule in the right upper lobe and multiple liver masses. He was diagnosed with synchronous primary lung adenocarcinoma and HCC. Atezolizumab, bevacizumab, carboplatin, and paclitaxel (ABCP) chemotherapy was efficacious for both tumors. ABCP chemotherapy may be a potential treatment option for synchronous primary lung adenocarcinoma and HCC.

Dexamethasone (DEX)-sparing strategies (one-day DEX) with palonosetron as doublet antiemetic prophylaxis have previously been studied. However, DEX-sparing regimens with 5-hydroxytryptamine-3 receptor antagonist (5-HT3RA) and aprepitant (APR), as triplet antiemetic prophylaxis, have not been evaluated. This study aimed to evaluate the efficacy of a combination of 5-HT3RA, APR, and DEX on day 1 of carboplatin (CBDCA)-based chemotherapy in patients with lung cancer. Data were pooled from a nationwide, multicenter, prospective observational study using propensity score–matched analysis to compare the incidence of chemotherapy-induced nausea and vomiting (CINV) between one- and multiple-day DEX regimens in combination with 5-HT3RA plus APR. Incidence of delayed nausea was significantly higher in the one-day than in the multiple-day DEX group. Incidence of nausea was also significantly higher in the one-day than in the multiple-day DEX group on days 3–5. Kaplan–Meier curves for nausea showed a significant difference between the two groups; however, there was no significant difference in the occurrence of vomiting or the Kaplan–Meier curves of time to vomiting. To the best of our knowledge, this study is the first to evaluate the efficacy of a DEX-sparing regimen by comparing one- and multiple-day DEX combined with 5-HT3RA and APR concerning CINV incidence in lung cancer patients receiving CBDCA-based chemotherapy. Antiemetic regimens of one-day DEX result in poor control of delayed nausea; therefore, we recommend the application of the DEX-sparing strategy only after careful patient selection while considering the development of nausea.

Background Patients with lung cancer who are treated with carboplatin-based chemotherapy regimens often experience chemotherapy-induced nausea and vomiting (CINV). However, knowledge on the effect of regimen and cofactors on the risk of CINV is limited. This study aimed to analyze and compare the incidence of CINV between lung cancer patients undergoing carboplatin plus pemetrexed (CBDCA+PEM) and those undergoing carboplatin plus paclitaxel (CBDCA+PTX) chemotherapy. Methods Pooled data of 240 patients from two prospective observational studies were compared using propensity score matching. Separate multivariate logistic regression analyses were used to identify risk factors for nausea and vomiting following chemotherapy. Results Delayed nausea was significantly more common in patients treated with CBDCA+PEM than in those treated with CBDCA+PTX (51.1% vs. 36.2%, P = 0.04), but the incidence of vomiting did not significantly differ between the two groups (23.4% vs. 14.9%, P = 0.14). The occurrence of CINV peaked on day 4 in the CBDCA+PTX group and on day 5 in the CBDCA+PEM group. Multivariate analysis showed that female sex, younger age, and CBDCA+PEM regimen were independent risk factors for delayed nausea, while female sex was an independent risk factor for delayed vomiting. Conclusions The CBDCA + PEM regimen has a higher risk of causing delayed nausea than the CBDCA + PTX regimen, and aggressive antiemetic prophylaxis should be offered to patients treated with CBDCA + PEM.

Delayed chemotherapy-induced nausea and vomiting (CINV) is not well controlled in colorectal cancer (CRC) patients undergoing oxaliplatin (L-OHP)-based chemotherapy. Whether neurokinin-1 receptor antagonist addition to a first-generation 5HT3 antagonist (1st 5-HT3 RA) and dexamethasone (DEX) is beneficial to these patients remains controversial. Furthermore, whether palonosetron (PALO) or aprepitant (APR) is more effective in controlling delayed CINV is unclear. We, therefore, investigated whether PALO+DEX or 1st 5-HT3 RA+DEX+APR was more effective in controlling delayed CINV, and the risk factors for delayed CINV, in CRC patients undergoing L-OHP-based chemotherapy. Data were pooled from two prospective observational Japanese studies and a phase III trial to compare CINV incidence between the PALO + DEX (PALO) and 5-HT3 RA+DEX+APR (APR) groups by propensity score-matched analysis. CINV risk factors were identified using logistic regression models. The CINV incidence was higher in the PALO group than in the APR group. Logistic regression analysis revealed alcohol consumption, motion sickness, and the PALO+DEX regimen as independent risk factors for delayed nausea, and female sex and the PALO+DEX regimen as those for delayed vomiting. Compared with prophylactic PALO + DEX, 1st 5-HT3 RA+DEX+APR was more effective in controlling delayed CINV. Thus, CRC patients receiving L-OHP-based chemotherapy should be treated with three antiemetics, including APR.

Delayed tissue plasminogen activator (tPA) treatment increases the risk of intracerebral hemorrhage in patients with ischemic stroke. We previously demonstrated that tPA treatment caused hemorrhagic complications in a 4-h middle cerebral artery occlusion (MCAO) mouse model when administered after reperfusion. In the present study, we administered an anti-high mobility group box 1 (αHMGB1) antibody to 4-h MCAO mice to evaluate the usability of αHMGB1 antibody treatment in the delayed phase of ischemia, beyond the therapeutic time window of tPA.αHMGB1 antibody, tPA and control IgG were dissolved in normal saline and administered intravenously into the tail vein of the mice after reperfusion. Infarct volume, hemorrhagic volume, brain swelling, functional outcomes and levels of pro-inflammatory cytokines, such as HMGB1, interleukin (IL)-6 and tumor necrosis factor (TNF)-α, were evaluated 24 h after MCAO.tPA treatment was not only ineffective but also caused a massive intracerebral hemorrhage. Treatment with αHMGB1 antibody reduced the infarct volume and swelling and ameliorated neurologic impairment and motor coordination without hemorrhagic complications by inhibiting HMGB1 activity. Moreover, the αHMGB1 antibody suppressed pathways of secondary inflammatory responses, such as IL-6 and TNF-α, after cerebral ischemia.These results indicate that αHMGB1 antibody may be therapeutically efficient in the delayed phase of ischemia, where tPA treatment is no longer an eligible option. Treatment with an αHMGB1 antibody may be an effective therapeutic option in patients who exceed the tPA therapeutic time window.

Correlations between the structural properties and nonradiative recombination (NRR) behaviors of threading dislocations in freestanding hydride-vapor-phase-epitaxy (HVPE) GaN substrates were investigated using cathodoluminescence (CL), the etch pit method, transmission electron microscopy (TEM), and multiple-photon excitation photoluminescence (MPPL). A statistical analysis with a one-to-one comparison of 480 CL dark spots (prior to etching) with their corresponding etch pits shows that all dislocation types act as NRR centers with a strong correlation between the NRR rate at the dislocation cores and the pit size. Further TEM observations accurately determined the magnitude and direction of Burgers vectors for dislocations under each type of etch pit, which firmly links the NRR behaviors with the dislocation type. It is found that a dislocation pair composed of (a + c) and (−a + c) threading mixed-type dislocations (TMDs) is the strongest NRR center among the considered dislocation types. The pair runs along the c-axis with a stable distance of 42 nm between them. This is followed by other types of TMD pairs, a + c TMDs, ma + nc TMDs (m and n are integers, m > 1 or n > 1), 1c threading screw dislocations, and 1a threading edge dislocations in descending order of NRR rates. Three-dimensional (3D) dislocation images visualized by MPPL revealed that most of the dislocations are nearly parallel to the c-axis, while the a + c TMDs are susceptible to large tilting. MPPL also indicates that the ma + nc TMDs may result from several merging dislocations.

The frequency dispersion in admittance measurements in AlGaN/GaN high-electron-mobility transistors, which is typically interpreted to result from an interface trap density Dit, is also known to be caused by effects other than Dit. To study the origin of two peaks of conductance component “ Gp/ ω” as a function of frequency in lateral gated diodes using AlGaN/GaN structures on Si wafers grown by metal–organic chemical vapor deposition, we measured capacitance C and conductance Gp/ ω–voltage V as a function of angular frequency ω ( C– ω– V and Gp/ ω– ω– V, respectively) of long-gate field-effect transistors with a varied gate length. We also simulated the C– ω– V and Gp/ ω– ω– V curves using an equivalent circuit that consisted of actually measured component parameters without Dit. We confirmed that the Gp/ ω– ω curves show two peaks caused by the two-dimensional electron gas channel resistance and the gate current leakage and quantitatively determined the two ωpeak positions and intensities. We also discussed the effect of acceptor concentration in the GaN channel-layer on lowering of ωpeak at weak inversion.

To accomplish a high-temperature operation of GaN/InGaN multiple-quantum-well (MQW) UV photodetectors (UV-PDs), the investigation of device performances at high-temperature regimes is truly essential. Therefore, in the present work, GaN/InGaN MQW-based UV-PDs on sapphire are fabricated and their photovoltaic and carrier transit time characteristics are investigated at different temperatures. Our results suggest that the temperature has a strong impact on various photovoltaic properties: we noticed an increase in short circuit current density and a significant lowering in open circuit voltage and power conversion efficiency when the ambient temperature increases from 25 to 300 °C. The time-dependent photo-response characteristics at different temperatures suggest that both the rise time and fall time are reduced at high temperatures, indicating the thermal activation of localized charges at an exacerbated temperature.

A crack-free indium gallium nitride (InGaN) based light emitting diode (LED) grown on silicon (Si) substrate was successfully demonstrated by introducing aluminium nitride/gallium nitride (AlN/GaN) superlattice structure (SLS) in the growth of the LED. The luminescence and the crystalline properties of the LED were discussed. From photoluminescence (PL) surface mapping measurement, the emission wavelength of the LED (453 nm) was almost uniform across the LED epi-wafer area. Temperaturedependent PL revealed that the dominant emission peak of the LED was 2.77 eV at all temperatures. The emission peak was related to the quantum wells of the LED. Some additional peaks were also observed, in particular at lower temperatures. These peaks were associated to alloy fluctuations in the In0.11Ga0.89N/ In0.02Ga0.98N multiquantum wells (MQWs) of the LED. Furthermore, the dependence of PL intensity and PL decay time on temperature revealed the evidence related to indium and/or interface fluctuations of the quantum wells. From X-ray diffraction (XRD) ω-scan measurements, fringes of the AlN/GaN SLS were clear, indicating the SLS were grown with good interface abruptness. However, the fringes for the MQWs were less uniform, indicating another evidence of the alloy fluctuations in the MQWs. XRD-reciprocal surface mapping (RSM) measurement showed that all epitaxial layers of the LED were grown coherently, and the LED was fully under strain.

Purpose The protective effect of magnesium (Mg) supplementation against cisplatin (CDDP)-induced nephrotoxicity has been widely described; however, the optimal dose of Mg supplementation is unclear. The aim of this study was to investigate whether 20 mEq of Mg supplementation is more effective than 8 mEq Mg in preventing CDDP-induced nephrotoxicity, as well as the associated risk factors, in cancer patients treated with CDDP-based chemotherapy. Methods Pooled data of 272 patients receiving 20 mEq or 8mEq Mg supplementation to CDDP-based chemotherapy from a multicenter, retrospective, observational study were compared using propensity score matching. Separate multivariate logistic regression analyses were used to identify the risk factors for renal failure induced by each treatment dose. Results There was no significant difference in the incidence of CDDP-induced nephrotoxicity between the 8 mEq and 20 mEq groups (18.4% vs. 20.6%, P = 0.760). There was also no significant difference in the severity of nephrotoxicity, elevated serum creatinine levels, and decreased estimated creatinine clearance levels between the two groups. Cardiac disease and albumin levels were identified as independent risk factors for CDDP-induced nephrotoxicity. Conclusion We did not find an advantage of 20 mEq over 8 mEq Mg supplementation in terms of a preventive effect against CDDP-induced nephrotoxicity. The optimal dose of Mg supplementation for the prevention of CDDP-induced nephrotoxicity remains unknown, and further studies are warranted.

This paper describes IEEE P7001, a new draft standard on transparency of autonomous systems1. In the paper, we outline the development and structure of the draft standard. We present the rationale for transparency as a measurable, testable property. We outline five stakeholder groups: users, the general public and bystanders, safety certification agencies, incident/accident investigators and lawyers/expert witnesses, and explain the thinking behind the normative definitions of “levels” of transparency for each stakeholder group in P7001. The paper illustrates the application of P7001 through worked examples of both specification and assessment of fictional autonomous systems.

Our previous study indicated that recombinant human soluble thrombomodulin (rhsTM) could attenuate brain damage when administered as a bolus in the cerebral ischaemic early phase. Then, we considered that treatment with rhsTM may show therapeutic effects even when administered in the ischaemic delayed phase, because rhsTM has an action of inhibiting high-mobility group box 1 (HMGB1) as a late mediator of lethal systemic inflammation. This study was performed to investigate the effects of delayed treatment with rhsTM on ischaemic brain damage induced by high HMGB1 level in mice subjected to 4-hour middle cerebral artery occlusion (MCAO). One day after MCAO, rhsTM was administered intraperitoneally at a dose of 1 or 5 mg/kg once a day for 7 days. Neurological score, motor coordination and HMGB1 levels were measured 1, 3 and 7 days after MCAO. The presence of activated microglia was evaluated 7 days after MCAO. Systemic HMGB1 levels increased 1 to 7 days after MCAO and were higher at 7 days compared with day 1. At the same time, survival rate decreased, and activated microglia increased in the infarct area. Treatment with rhsTM improved neurological score, motor coordination, survival and prevented brain damage. Moreover, rhsTM decreased both HMGB1 level and number of activated M1 microglia. The results of this study indicated that rhsTM improved functional outcomes via inhibition of HMGB1 up-regulation and M1 microglial activation in the cerebral ischaemic delayed phase. rhsTM may become a new therapeutic agent with a wide therapeutic time window in patients with cerebral ischaemia.

300-nm-thick AlInN films with InN molar fractions ranging from 0.114 to 0.197 were grown by metalorganic chemical vapor deposition on c-plane GaN on sapphire. It was confirmed that no lattice relaxation occurred for samples with InN molar fractions from 0.144 to 0.197, and the InAlN films with low InN molar fractions showed a relative smooth surface. However, it turned into a granular surface morphology resulting from a columnar polycrystalline structure when the InN molar fraction exceeded a compositional boundary of in-plane lattice matching. As for the smooth-surface AlInN single-layers, the optical constants as well as energy bandgaps were determined.

As one of the strategies for the early detection and treatment of osteoporosis, we have recommended visiting a hospital, based on the Fracture Risk Assessment Tool (FRAX®) and evaluation questionnaire for osteoporotic fracture risk. In this study, we evaluated the impact of intervention by community pharmacists by integrating our data for the FRAX® and questionnaire. The measurement of FRAX® and the questionnaire survey were conducted through participation in health seminars organized by a community general support center from June 2018 to December 2019. Participants with a FRAX® score more than 15% and at least one item in the questionnaire were considered to have "suspected osteoporosis" were recommended medical consultation. The medical treatment status for the participants considered to have "suspected osteoporosis" aged 40-90 years were analyzed. Of the 84 participants, 54 had a FRAX® score more than 15%, and 44 participants fulfilled at least one item in the questionnaire. Medical consultation was recommended to 26 of these 44 participants, excluding 18 under treatment. Of the 25 participants, six (excluding one who disagreed) received consultation, and medical treatment was started for four of them (66.7%). However, consultation with the attending physician was recommended to five of the 18 participants who were initially on treatment but discontinued it at the time of the survey. Consequently, two participants resumed their osteoporosis treatment. Our data suggest advantages of community pharmacists' intervention using FRAX® and a questionnaire for osteoporotic fracture risk measurement for early detection and medical treatment.

Delayed chemotherapy‐induced nausea and vomiting (CINV) is not well controlled in colorectal cancer (CRC) patients undergoing oxaliplatin (L‐OHP)‐based chemotherapy. Whether neurokinin‐1 receptor antagonist addition to a first‐generation 5HT3 antagonist (1st 5‐HT3RA) and dexamethasone (DEX) is beneficial to these patients remains controversial. Furthermore, whether palonosetron (PALO) or aprepitant (APR) is more effective in controlling delayed CINV is unclear. We, therefore, investigated whether PALO+DEX or 1st 5‐HT3RA+DEX+APR was more effective in controlling delayed CINV, and the risk factors for delayed CINV, in CRC patients undergoing L‐OHP–based chemotherapy. Data were pooled from two prospective observational Japanese studies and a phase III trial to compare CINV incidence between the PALO + DEX (PALO) and 5‐HT3RA+DEX+APR (APR) groups by propensity score–matched analysis. CINV risk factors were identified using logistic regression models. The CINV incidence was higher in the PALO group than in the APR group. Logistic regression analysis revealed alcohol consumption, motion sickness, and the PALO+DEX regimen as independent risk factors for delayed nausea, and female sex and the PALO+DEX regimen as those for delayed vomiting. Compared with prophylactic PALO + DEX, 1st 5‐HT3RA+DEX+APR was more effective in controlling delayed CINV. Thus, CRC patients receiving L‐OHP–based chemotherapy should be treated with three antiemetics, including APR., This study demonstrates that the triplet antiemetic prophylaxis with first‐generation 5HT3 receptor antagonist plus dexamethasone plus aprepitant was more effective in controlling delayed chemotherapy‐induced nausea and vomiting (CINV) compared with prophylaxis with palonosetron plus dexamethasone in colorectal cancer patients receiving oxaliplatin‐based chemotherapy.