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Aims To examine the effects of a 24-month treatment with ipragliflozin on carotid intima-media thickness (IMT) in type 2 diabetes patients. Methods and results In this multicenter, prospective, randomized, open-label, and blinded-endpoint investigator-initiated clinical trial, adults with type 2 diabetes and haemoglobin A1C (HbA1c) of 6.0–10.0% (42–86 mmol/mol) were randomized equally to ipragliflozin (50 mg daily) and non-sodium-glucose cotransporter-2 (SGLT2) inhibitor use of standard-care (control group) for type 2 diabetes and were followed-up to 24 months. The primary endpoint was the change in mean common carotid artery IMT (CCA-IMT) from baseline to 24 months. A total of 482 patients were equally allocated to the ipragliflozin (N = 241) and control (N = 241) groups, and 464 patients (median age 68 years, female 31.7%, median type 2 diabetes duration 8 years, median HbA1c 7.3%) were included in the analyses. For the primary endpoint, the changes in the mean CCA-IMT from baseline to 24 months were 0.0013 [95% confidence interval (CI), −0.0155–0.0182] mm and 0.0015 (95% CI, −0.0155–0.0184) mm in the ipragliflozin and control groups, respectively, with an estimated group difference (ipragliflozin-control) of −0.0001 mm (95% CI, −0.0191–0.0189; P = 0.989). A group difference in HbA1c change at 24 months was also non-significant between the treatment groups [−0.1% (95% CI, −0.2–0.1); P = 0.359]. Conclusion Twenty-four months of ipragliflozin treatment did not affect carotid IMT status in patients with type 2 diabetes recruited in the PROTECT study, relative to the non-SGLT2 inhibitor-use standard care for type 2 diabetes.

The emergence and prevalence of antimicrobial-resistant bacteria in wild animals are a great concern for public health. A total of 963 Escherichia coli isolates from 475 wild mammals (242 sika deers, 112 wild boars, 113 small mammals, 4 Japanese badger, 2 Tokara cows, and 2 Amani rabbits), collected between 2013 and 2017, were examined for antimicrobial susceptibility. Resistance to at least one antimicrobial was observed in 92 of 963 isolates (9.3%). No isolates exhibited resistance to carbapenem (meropenem). Resistance to third-generation cephalosporin (cefotaxime) and fluoroquinolone (ciprofloxacin) was observed in less than 1% of the isolates. Thus, low prevalence of bacterial antimicrobial resistance was observed in wild mammals between 2013 and 2017 in Japan.

The clinical dosing method for tolvaptan in patients with acute heart failure (HF) is still unclear. We aimed to compare the differences in clinical effect between two dosing regimens: once-daily 7.5mg and twice-daily 3.75mg.In this randomized trial, tolvaptan was administered within 12h from hospital admission. The primary outcome was the serial change in congestion scores measured every day from enrollment until dosing day 7. Outcomes including safety parameters were also evaluated.The subjects were assigned to either the once-daily 7.5mg dosing regimen (N=15) or the twice-daily 3.75mg dosing regimen (N=16). The time-course changes in body weight, serum sodium and creatinine levels, systolic blood pressure, daily urine output, and congestion scores were similar between the two groups. In the twice-daily 3.75mg dosing group, the serum sodium levels on days 3 and 4 were significantly (p0.05) increased compared with those on day 1. The congestion scores significantly (p0.05) decreased from day 2 to day 7 in both groups compared with those on day 1. However, the difference in the serial change in the congestion scores did not reach statistical significance.Our present results suggest that the early administration of tolvaptan within 12h after hospital admission significantly improved congestion from the first day after administration by either dosing regimen, i.e. once-daily 7.5mg or twice-daily 3.75mg in patients with acute HF.

This paper investigates the international business literature of the last forty years from the incorporation of the term global cities as a reference in the construction of new theoretical contributions. A bibliometric method was performed in two stages. In the first one, the main areas of knowledge and the seminal studies addressing the concept were identified. Most research focuses on economic geography and urban studies. In the second, the approaches used specifically in international business were organized in the main journals of the area. The results show that the studies on global cities are still incipient, highlighting, among the approaches, the relation between location advantages and specific aspects of the multinational company. In addition, there is a growing interest in the development of analyzes at the subnational level represented by global cities, from different aspects such as the choice of entry mode, the role of advanced service firms, the importance of networks and the process of knowledge transfer. The combination of the perspectives of economic geography and international business, although claimed by scholars from both areas, still lacks a more robust theoretical and empirical body in regard to cities as centers of attractiveness of foreign investment in global markets. In analyzing the importance of the phenomenon of global cities, this study contributes to a better understanding of the contemporary internationalization strategies of multinational companies, highlighting the interdisciplinary potential between international business theories and economic geography., Este artigo investiga a literatura de negócios internacionais dos últimos quarenta anos a partir da incorporação do termo cidades globais como referencial na construção de novos aportes teóricos. Foi realizada uma pesquisa bibliométrica em duas etapas. Na primeira, foram identificadas as principais áreas de conhecimento e os estudos seminais abordando o conceito. A maior parte das pesquisas concentram-se na geografia econômica e nos estudos urbanos. Na segunda, foram organizadas as abordagens utilizadas especificamente em negócios internacionais nos principais periódicos da área. Os resultados demonstram que os estudos sobre cidades globais são ainda incipientes destacando-se, dentre as abordagens, a relação entre vantagens de localização e aspectos específicos da empresa multinacional. Existe crescente interesse no desenvolvimento de análises em nível subnacional representado pelas cidades globais, a partir de diferentes aspectos como a escolha do modo de entrada, o papel das empresas de serviços avançados, a importância das redes e o processo de transferência de conhecimento. A combinação entre as perspectivas da geografia econômica e de negócios internacionais, embora reivindicada há algum tempo por estudiosos de ambas as áreas, ainda carece de um corpo teórico e empírico mais robusto no que se refere as cidades como centros de atratividade de investimentos estrangeiros em mercados globais. Ao analisar a importância do fenômeno das cidades globais, o estudo contribui para melhor compreensão das estratégias contemporâneas de internacionalização das empresas multinacionais, ressaltando o potencial interdisciplinar entre as teorias de negócios internacionais e geografia econômica.

While sorafenib (SFN) is the established worldwide standard therapeutic agent for advanced hepatocellular carcinoma (HCC), hepatic arterial infusion chemotherapy (HAIC) is also considered a favorable treatment for some advanced HCCs. This study aimed to evaluate each treatment and provide an optimal therapeutic choice for advanced HCCs. We analyzed 72 patients treated with SFN and 128 patients receiving HAIC. Both treatment groups were analyzed for prognostic and disease progression factors, and matched pair analysis was performed using the propensity score matching method. The preferable status of intrahepatic lesions, that is, no lesions or only a single (5 cm) and low albumin (≤3.4 g/dL) were poor prognostic and disease progression factors in the HAIC group. Analysis of 53 patients selected from each of the SFN and HAIC groups based on the propensity score matching method showed no significant differences in survival or disease progression between the two matched subgroups. On the other hand, progression-free survival (PFS) in the HAIC-matched subgroup was significantly longer than in the SFN-matched subgroup, particularly in patients with portal vein invasion (PVI) and/or without extrahepatic spread (EHS). The treatment efficacy of HAIC is similar to that of SFN regarding survival and disease progression. Longer PFS might be expected for HAIC compared with SFN, particularly in patients with PVI and/or without EHS.

複合酸化物, Sr0.14Ca0.86CuO2, SrCuO2およびCaCuO2をSrCO3, CaCO3およびCuOから焼結法によって作製した。試料粉末は粘度の異なるパラフィン系鉱油に添加し, 油境界潤滑下におけるこれらの潤滑特性を Falex 型試験機で評価した。その結果, これら複合酸化物粉末を鉱油に添加することで, 低粘度油でもその潤滑性が改善された。また, その時の添加量は2～5mass%の低濃度で効果を示し, 耐焼付き性および低摩擦係数が得られた。これらの潤滑特性は油性剤および分散剤としてのオレイン酸をともに用いることでさらに向上する。特に, 無限層構造をもつSr0.14Ca0.86CuO2は, 低粘度基油でさえもオレイン酸を併用することで, よりよい摩擦摩耗特性を示した。

A numerical simulation method has been developed for predicting the maneuvering motion of blunt ships by solving the equations of motion with the Navier-Stokes equations. Since coordinate system is fixed to an arbitrarily moving ship, inertia forces must be incorporated into the NS equation as body forces. The hydrodynamic forces acting on the hull of the ship are obtained by solving the incompressible and time-dependent NS equations numerically. The hydrodynamic forces caused by rudder and propeller and their interactions with the hull are calculated by the mathematical model. This method was applied to the simulations of the 10-degree Z maneuvering motion of two VLCC models with the same principal dimensions and different aft-part frame lines, that is, one is so-called V-shaped and the other is U-shaped. The results of the simulations agreed well with those of model tests and revealed the typical difference in maneuverability between the two ships.

To investigate the effect of attention and novelty change of stimulus, modulation of evoked potentials following electrical tooth stimulus (EP-TS) and finger stimulus (EP-FS) by selective attention task were studied in 17 healthy adult volunteers. Stimulus in this study were electrical tooth and finger stimulus, tone beep in constant (2.0 sec.) interval in random order, and delivering percentage of tooth and finger stimulus was 10, 20, 30, 40, and 50% and tone beep was 80, 60, 40, 20, and 0%. The results were as follows: 1) P2 latency and N 2-P2 amplitude were increased while the subject's attention was toward each stimulus (attention), decreased while the subject's attention was not toward each stimulus (non-attention) at EP-TS and EP-FS. 2) When paying attention, P 2 latency and N 2-P 2 amplitude were increased as delivering percentage of tooth and finger stimulus were decreased. These findings suggested that attention and novelty change of stimulus when paying attention were one of the factors that influence psychological factors and modulate EP-TS and EP-FS results.