A pharmacokinetics and safety phase 1/1b study of oral ixazomib in patients with multiple myeloma and severe renal impairment or end-stage renal disease requiring haemodialysis.

Renal impairment (RI) is a major complication of multiple myeloma (MM). This study aimed to characterize the single-dose pharmacokinetics (PK) of the oral proteasome inhibitor, ixazomib, in cancer patients with normal renal function [creatinine clearance (CrCl) ≥90 ml/min; n = 20), severe RI (CrCl <30 ml/min; n = 14), or end-stage renal disease requiring haemodialysis (ESRD; n = 7). PK and adverse events (AEs) were assessed after a single 3 mg dose of ixazomib. Ixazomib was highly bound to plasma proteins (~99%) in all renal function groups. Unbound and total systemic exposures of ixazomib were 38% and 39% higher, respectively, in severe RI/ESRD patients versus patients with normal renal function. Total ixazomib concentrations were similar in pre- and post-dialyser samples collected from ESRD patients; therefore, ixazomib can be administered without regard to haemodialysis timing. Except for anaemia, the incidence of the most common AEs was generally similar across groups, but grade 3 and 4 AEs were more frequent in the severe RI/ESRD groups versus the normal group (79%/57% vs. 45%), as were serious AEs (43%/43% vs. 15%). The PK and safety results support a reduced ixazomib dose of 3 mg in patients with severe RI/ESRD

ハイキブツ ショブンジョウ ニ オケル ジュウキンゾク ノ イドウセイ ト ネンド ライナー ノ トウスイ ケイスウ ニ オヨボス サンカ カンゲン ハンノウ ノ エイキョウ

京都大学0048新制・課程博士博士(工学)甲第9554号工博第2140号新制||工||1234(附属図書館)UT51-2002-G312京都大学大学院工学研究科土木工学専攻(主査)教授 嘉門 雅史, 教授 大西 有三, 教授 森澤 眞輔学位規則第4条第1項該当Doctor of EngineeringKyoto UniversityDA

Microbial Redox Effects on the Attenuation of Fe and Zn in Landfill Leachate Plume

廃棄物処分場の浸出水に含まれる金属イオンを対象として, 微生物活動による還元反応およびpHが粘土層による亜鉛および鉄の緩衝作用に与える影響を実験的に検討した。その結果, 嫌気性/脱窒/鉄イオン還元条件下において, 亜鉛はpH=7以下の場合に溶解性を示し, pH=7.2以上の場合は水酸化亜鉛および炭酸亜鉛の沈殿を形成した。また, 硫酸還元状態下においては硫化亜鉛を形成した。一方, 鉄については嫌気性/脱窒/自然条件のpH下においては溶解性を示さず, 鉄イオン還元/硫酸還元条件において溶解性が上昇する傾向が観察された。このことは, pHが中性域で酸化還元電位が非常に低い環境下にある廃棄物処分場おいては, 鉄は溶解するものの、有害重金属である亜鉛は水溶性を示さないと推測できる。Modified batch tests were conducted to evaluate the bacteria-induced redox and pH effects on the attenuation of iron and zinc in landfill site. Test results show that under aerobic, denitrification, and Fe(III) reduction conditions, zinc was soluble when pH7.2. Under sulfate reduction conditions, zinc sulfides were formed. Iron was insoluble under aerobic, denitrification, and natural pH conditions. Elevated soluble iron was observed in Fe(III) reduction and sulfate reduction conditions. A combination of nearly neutral pH and extremely low Eh conditions tends to promote zinc insolubilization but iron solubilization in landfill sites.廃棄物処分場の浸出水に含まれる金属イオンを対象として,微生物活動による還元反応およびpHが粘土層による亜鉛および鉄の緩衝作用に与える影響を実験的に検討した。その結果,嫌気性/脱窒/鉄イオン還元条件下において,亜鉛はpH=7以下の場合に溶解性を示し,pH=7.2以上の場合は水酸化亜鉛および炭酸亜鉛の沈殿を形成した。また,硫酸還元状態下においては硫化亜鉛を形成した。一方,鉄については嫌気性/脱窒/自然条件のpH下においては溶解性を示さず,鉄イオン還元/硫酸還元条件において溶解性が上昇する傾向が観察された。このことは,pHが中性域で酸化還元電位が非常に低い環境下にある廃棄物処分場おいては,鉄は溶解するものの、有害重金属である亜鉛は水溶性を示さないと推測できる。Modified batch tests were conducted to evaluate the bacteria-induced redox and pH effects on the attenuation of iron and zinc in landfill site. Test results show that under aerobic, denitrification, and Fe(III) reduction conditions, zinc was soluble when pH7.2. Under sulfate reduction conditions, zinc sulfides were formed. Iron was insoluble under aerobic, denitrification, and natural pH conditions. Elevated soluble iron was observed in Fe(III) reduction and sulfate reduction conditions. A combination of nearly neutral pH and extremely low Eh conditions tends to promote zinc insolubilization but iron solubilization in landfill sites

Approach for Measuring Swelling Stress of Buffer Backfilling Material

Abstract: The characteristics of swelling stress of buffer backfilling material have been studied by forcebalance method and constant volume test method in this paper. The constant volume test apparatus was designed by the authors. Results show that swelling stress changing with time is a little different between the two methods. The value of swelling stress measured by constant volume test is more accurate; besides, uptaking water with time could also be monitored by constant volume test. The constant volume test method is more suitable for measuring the swelling stress of buffer backfilling material

Compacted sewage sludge as a barrier for tailings: the heavy metal speciation and total organic carbon content in the compacted sludge specimen.

Acid mine drainage (AMD) was the main environmental problem facing the mining industry. For AMD had high heavy metals content and low pH, the compacted sewage sludge might be a barrier for tailings whose oxidation and weathering produced AMD, with its own carbon source, microorganism reduction ability and impermeability. To study the heavy metals environmental risk, under the simulate AMD, the deionized water (DW), and the pH 2.1 sulfuric acid water (SA) seepage conditions, respectively, the changes of the chemical speciation of heavy metals Cd, Cu, Fe, Ni, Zn and total organic carbon (TOC) content in the compacted sewage sludge were assessed in the different periods. The results indicated according to the distribution of heavy metals, the potential mobility was for Cd: 6.08 under AMD, 7.48 under SA, ∞ under DW; for Cu: 0.08 under AMD, 0.17 under SA, 0.59 under DW; for Fe: 0.15 under AMD, 0.22 under SA, 0.22 under DW; for Ni: 2.60 under AMD, 1.69 under SA, 1.67 under DW; and for Zn: 0.15 under AMD, 0.23 under SA and 0.21 under DW at the second checking time. TOC content firstly decreased from 67.62±0% to 66.29±0.35%, then increased to 67.74±0.65% under the AMD seepage while TOC decreased to 63.30±0.53%, then to 61.33±0.37% under the DW seepage, decreased to 63.86±0.41%, then to 63.28±0.49% under SA seepage. That indicated under the AMD seepage, the suitable microorganisms communities in the compacted sewage sludge were activated. And the heavy metals environmental risk of compacted sewage sludge was lower with AMD condition than with other two. So the compacted sewage sludge as a barrier for tailings was feasible as the aspect of environmental risk assessment

Stability coefficient analysis of soil slopes with non-linear topography based on the ratio of internal to external power

The limit analysis of slope stability has a relatively higher calculation efficiency and accuracy because it ignores the constitutive relation of materials. Compared to the limit equilibrium method, its assumptions are strict and realistic. In the classical upper bound limit analysis, the slope surfaces are required to be a regular straight line. However, the surfaces of natural or cutting slopes are normally nonlinear. In addition, the stability number Ns=c/γH is used to calculate the critical height of slopes without considering the external power caused by pore pressure. Different from the static equilibrium conditions adopted by the traditional limit equilibrium method, this paper aimed to evaluate the stability of slopes with nonlinear surfaces based on kinetic analysis. First, a method for determining the rotation center of landslides with nonlinear surfaces based on upper bound limit analysis and the principle of virtual work was proposed. Second, it was assumed that the sliding surface was a logarithmic helix, and the virtual work under gravity and energy equilibrium equation of slopes were established. Third, the stability coefficient K defined by the ratio of internal power to external power was proposed to evaluate the stability of the slope, and the results were compared with the Bishop method to verify its effectiveness. The influences of slope degree (β), internal friction angle (φ), cohesion (c) and pore pressure coefficient (ru) on the stability coefficient K of different natural and cutting slopes were analyzed. The results confirmed that the stability of steep slopes would be improved by cutting. The stability coefficient K increased with increasing cohesion and decreased with increasing pore water pressure coefficient. When the impact of cohesion on the stability coefficient K was more significant than that on the pore water pressure coefficient, K increased with increasing internal friction angle (φ). In contrast, the stability coefficient K decreases with increasing internal friction angle (φ). The above results followed the general understanding of slope stability analysis, and the rationality of the model was verified. By comparing the calculation results with the Bishop method, it was found that the intension of the critical state represented by safety factor FS=1 was the same as the stability coefficient K=0 defined in this paper. The stability coefficient K increased nonlinearly with increasing cohesion, which was in line with the progressive failure mode of the soil slopes

On isolated singularities of Kirchhoff equations

In this note, we study isolated singular positive solutions of Kirchhoff equatio

Ressam Akdik dün vefat etti

Taha Toros Arşivi, Dosya No: 19-Akdik, Kamil-Şeref-Muhittin-SaraUnutma İstanbul projesi İstanbul Kalkınma Ajansı'nın 2016 yılı "Yenilikçi ve Yaratıcı İstanbul Mali Destek Programı" kapsamında desteklenmiştir. Proje No: TR10/16/YNY/010

Porewater salinity effect on flocculation and desiccation cracking behaviour of kaolin and bentonite considering working condition

International audienceCracking behaviour of clays at a local working climate and soils' evolution under seepage boundary is very important for the geological engineering. In coastal regions, pore water salinity is incorporated into above processes. In this study, the properties of typical clays (kaolin and bentonite) in saline environments, including the consistency limits, particle sedimentation and crack pattern, were investigated. The consistency limits of kaolin remain constant regardless of the pore water salinity, while the liquid limits of bentonite noticeably decrease with increasing salinity. Flocculation of kaolin occurs in both distilled water and NaCl solution, whereas the fine particles in bentonite disperse in distilled water but aggregate in saline water. At the end of the evaporation process, the total crack area of bentonite is obviously decreased, and the total crack length increases with pore water salinity, whilst that of kaolin is not influenced. In the subsequent wetting process, the bentonite clods disperse easily in saline environment, but the collapse of kaolin clods is not significantly influenced by the water salinity. The above observations are explained by the initial aggregation of clay platelets for the interactive forces between particles