Search

Atezolizumab plus bevacizumab combination therapy (Atezo + Beva) is currently positioned as the first-line therapy for unresectable hepatocellular carcinoma (u-HCC). It may be difficult to decide whether to continue this treatment if radiological response is assessed as stable disease (SD). Therefore, the relationship between radiological response and prognosis was analyzed. A total of 109 patients with u-HCC and Child–Pugh Score of 5–7 received this treatment. Radiological response was assessed using Response Evaluation Criteria in Solid Tumors (RECIST) and modified RECIST at the first and second evaluations. Of SD patients (n = 71) at the first RECIST evaluation, partial response, SD, and progressive disease (PD) were seen in 10, 55, and 6 patients, respectively, at the second evaluation. On multivariate analysis, in patients with SD at the first RECIST evaluation, a 25% or greater increase in the alpha-fetoprotein (AFP) value from initiation of treatment (odds ratio, 7.38; p = 0.037) was the independent factor for PD at the second evaluation. In patients with SD (n = 59) at the second RECIST evaluation, decreased AFP from initiation of treatment (hazard ratio, 0.46; p = 0.022) was the independent factor related to progression-free survival on multivariate analysis. AFP trends could help decide the Atezo + Beva treatment strategy.

Background Sepsis occurs as a result of dysregulated host response to infection. However, cytokine adsorption therapy may restore the balance of proinflammatory and anti-inflammatory mediator responses in patients with sepsis. This study aimed to determine the cytokine adsorption ability of two different types of continuous renal replacement therapy (CRRT) hemofilters for polyethyleneimine-coated polyacrylonitrile (AN69ST) (surface-treated) and polymethylmethacrylate (PMMA) CRRT. Methods We performed a randomized controlled trial among sepsis patients undergoing CRRT, who were randomly assigned (1:1) to receive either AN69ST or PMMA-CRRT. The primary outcome was cytokine clearance of hemofilter adsorption (CHA). The secondary endpoints were the intensive care unit (ICU) and 28-day mortalities. Results We randomly selected 52 patients. Primary outcome data were available for 26 patients each in the AN69ST-CRRT and PMMA-CRRT arms. The CHA of high-mobility group box 1, tumor necrosis factor, interleukin (IL)-8, monokine induced by interferon-γ, and macrophage inflammatory protein were significantly higher in the AN69ST-CRRT group than in the PMMA-CRRT group (P P P P P P P = 0.26). Conclusion AN69ST and PMMA membranes have different cytokine CHA in patients with sepsis. Therefore, these two hemofilters may have to be used depending on the target cytokine. Trial registration This study was registered in the University Hospital Medical Information Network on November 1, 2017 (Trial No: UMIN000029450, https://center6.umin.ac.jp).

Background Endoscopic injection sclerotherapy (EIS) and endoscopic variceal ligation (EVL) are hallmark treatments for esophageal varices. Protein energy malnutrition can worsen when dietary restrictions are a required part of these treatments for patients with liver cirrhosis (LC). The aim of this study was to evaluate the effect of supplemental branched-chain amino acid-enriched nutrients (BCAA-EN) during EIS or EVL. Methods We retrospectively analyzed patients with LC who underwent EIS or EVL in our hospital from November 2008 to January 2016. Of the 55 eligible patients, 15 received a restricted diet and the remaining 40 patients received a restricted diet plus supplemental BCAA-EN during EIS or EVL. To reduce selection bias, we used one-to-two propensity score matching; 14 patients were assigned to a control group, and 28 were assigned to a BCAAEN group. Various blood chemistry parameters were measured and compared before and after treatment. Results Albumin concentrations in serum declined significantly in the control group but not in the BCAA-EN group. In patients with a Child-Pugh score of 5, albumin in serum did not decrease significantly in either group, although it did decrease in patients with a Child-Pugh score of 6 or more in the control group and was maintained in the BCAA-EN group. Multivariate analysis showed that only supplemental BCAA-EN was associated with the maintenance of albumin in serum. Conclusions Supplemental BCAA-EN would be effective in the maintenance of albumin in the serum of patients undergoing EIS or EVL, particularly for patients with advanced liver dysfunction.

The structure design of mechanical parts and components has been a significant theme of design automation. Today, topology optimization techniques have become relevant for effectively embodying optimal geometries of structures. However, their optimality is restricted to a particular category through design conditions, parameters, and optimization settings. When viewing the structure design as conceptual design, identifying the optimal category is essential rather than precise details. The category means configuration, morphology, or form rather than shape or geometry. This paper proposes a conceptual structure design framework for overcoming this gap. The framework considers that conceptual design results from classifying potentially possible geometries and identifying the best appropriate category from them. In detail, a topology optimization technique generates diverse optimal geometries under various settings of conditions and parameters, a deep clustering technique, i.e., the variational deep embedding, clusters them into several categories, and a logistic regression technique retrieves the criteria that distinct respective categories as design knowledge. A designer can interactively identify the relevant criteria that lead to the optimal structure for the design requirement by simultaneously revealing and refining those criteria under the retrieved knowledge. This paper applies the framework to a simple bridge design problem to demonstrate its validity and possibilities.

A 32–year–old man with dry cough was admitted to a hospital for suspected coronavirus disease–induced pneumonia. The SARS–CoV–2 PCR test showed positive results on day 3 after symptom onset. Mechanical ventilation and venovenous extracorporeal membrane oxygenation (VV ECMO) were initiated for respiratory function deterioration on day 8 after symptom onset. However, ECMO did not maintain adequate oxygenation, and ventilator settings did not allow lung rest. Therefore, secondary ECMO transport was performed, and the patient was transferred to our center via ECMOnet. The reduced oxygenation level was attributed to the use of a small drainage cannula with consequently reduced ECMO circulation. Replacement of the small drainage cannula was unsafe; therefore, an additional drainage cannula was inserted, and the ECMO configuration was switched to VV–V ECMO, which established sufficient ECMO circulation and improved his oxygenation levels, and ventilator settings were modified for lung rest. He was weaned off ECMO on day 14, and retransferred to the previous hospital on day 21 after symptom onset. Selection of a drainage cannula of optimal size is important in patients who receive VV ECMO support. Conversion of a VV ECMO to VV–V ECMO configuration is useful in cases of insufficient ECMO blood flow.

Heat exchangers are devices that typically transfer heat between two fluids. The performance of a heat exchanger such as heat transfer rate and pressure loss strongly depends on the flow regime in the heat transfer system. In this paper, we present a density-based topology optimization method for a two-fluid heat exchange system, which achieves a maximum heat transfer rate under fixed pressure loss. We propose a representation model accounting for three states, i.e., two fluids and a solid wall between the two fluids, by using a single design variable field. The key aspect of the proposed model is that mixing of the two fluids can be essentially prevented without any penalty scheme. This is because the solid constantly exists between the two fluids due to the use of the single design variable field. We demonstrate the effectiveness of the proposed approach through three-dimensional numerical examples in which an optimized design is compared with a simple reference design, and the effects of design conditions (i.e., Reynolds number, Prandtl number, design domain size, and flow arrangements) are investigated., Comment: 19 pages, 17 figures

The objective of conventional topology optimization is to optimize the material distribution for a prescribed design domain. However, solving the topology optimization problem strongly depends on the settings specified by the designer for the shape of the design domain or their specification of the boundary conditions. This contradiction indicates that the improvement of structures should be achieved by optimizing not only the material distribution but also the additional design variables that specify the above settings. We refer to the additional design variables as external variables. This paper presents our work relating to solving the design problem of topology optimization incorporating external variables. The approach we follow is to formulate the design problem as a multi-level optimization problem by focusing on the dominance-dependence relationship between external variables and material distribution. We propose a framework to solve the optimization problem utilizing the multi-level formulation and metamodeling. The metamodel approximates the relationship between the external variables and the performance of the corresponding optimized material distribution. The effectiveness of the framework is demonstrated by presenting three examples.

The present study retrospectively evaluated the efficacy of stereotactic body radiation therapy (SBRT), including repeated SBRT, for hepatocellular carcinoma. Participants comprised 220 HCC patients treated with SBRT in Hiroshima University Hospital between December 2008 and December 2021. Median overall survival (OS) and disease-free survival were 52 months (range, 45–64 months) and 17 months (range, 14–23 months), respectively. The 5-year local tumor recurrence rate was 3.4% (95% confidence interval (CI), 1.3–6.9%). Fifty-three patients underwent repeated SBRT (twice, 53 cases; three times, 10 cases; four times, 4 cases; five times, 1 case). Median interval between first and second SBRT was 20 months. Median OS from first SBRT was 76 months (95% CI, 50–102 months). Among patients with repeated SBRT, only one case showed local recurrence after second SBRT. Albumin–bilirubin score increased significantly from 6 to 12 months after repeated SBRT, both in the same segment and in remote segments, but the increase was not significant in the same segment. Only one case of grade 3 bile duct stricture was observed in patients who were treated with repeated SBRT. In conclusion, repeated SBRT provides good local control and a low risk of side effects.

Transarterial chemoembolization (TACE) has been the standard treatment for intermediate-stage, unresectable hepatocellular carcinoma (u-HCC). However, with recent advances in systemic therapy and the emergence of the concept of TACE-refractory or -unsuitable, the effectiveness of systemic therapy, as well as TACE, has been demonstrated for patients judged to be TACE-refractory or -unsuitable. In this study, the efficacy of lenvatinib and its combination with TACE after lenvatinib was investigated in 140 patients with intermediate-stage u-HCC treated with lenvatinib mainly because of being judged to be TACE-refractory or -unsuitable. Median overall survival (OS) and progression-free survival (PFS) were 24.4 and 9.0 months, respectively, indicating a good response rate. In multivariate analysis, modified albumin–bilirubin (mALBI) grade and up to seven criteria were identified as independent factors for OS, and mALBI grade and tumor morphology were identified as independent factors for PFS. While 95% of all patients were TACE-refractory or -unsuitable, the further prognosis was prolonged by the combination with TACE after lenvatinib initiation. These findings suggest that systemic therapy should be considered for intermediate-stage u-HCC, even in patients judged to be TACE-refractory or -unsuitable. The use of TACE after the start of systemic therapy may further improve prognosis.

This paper proposes a framework for generating design concepts through the loop of comprehensive exploitation and consequent exploration. The former is by any sophisticated optimization such as topology optimization with diversely different. The latter realization is due to the variational deep embedding (VaDE), a deep learning technique with classification capability. In the process of design concept generation first, exploitation through computational optimization generates various possibilities of design entities. Second, VaDE learns them. This learning encodes the clusters of similar entities over the latent space with smaller dimensions. The clustering result reveals some design concepts and identifies voids where as-yet-unrecognized design concepts are prospective. Third, the decoder of the learned VaDE generates some possibilities for new design entities. Forth such new entities are examined, and relevant new conditions will trigger further exploitation by the optimization. In this paper, this framework is implemented for and applied to the conceptual design problem of bridge structures. This application demonstrates that the framework can identify voids over the latent space and explore the possibility of new concepts. This paper brings up some discussion on the promises and possibilities of the proposed framework.

In this study, we present a framework based on the concept of multifidelity design optimization with the purpose of indirectly solving complex—computationally heavy and/or unstable—topology optimization problems. Our primary idea is to divide an original topology optimization problem into two types of subproblems for low-fidelity optimization and high-fidelity evaluation. To realize this idea, artificial design parameters, which we refer to as seeding parameters, are incorporated into the low-fidelity optimization problem for generating various patterns of topology-optimized candidates. The low-fidelity optimization problem is deliberately formulated as an easily solvable one by decreasing the nonlinearity of the original physical phenomena. Notably, selecting valid seeding parameters in the low-fidelity optimization problem is essential for employing the proposed framework. The aim of high-fidelity evaluation is to obtain a satisfactory solution using a high-fidelity analysis model, which considers the nonlinearity of the original physical phenomena, from the data set of the topology-optimized candidates, via the design of experiments. We apply the proposed framework to two case studies of isothermal and thermal turbulent flow problems, and discuss its efficacy as an alternative strategy for solving complex topology optimization problems.

The 11th Symposium on Polar Science/Ordinary sessions: [OG] Polar Geosciences, Wed. 2 Dec.

In this paper, we propose a sensitivity-free and multi-objective structural design methodology called data-driven topology design. It is schemed to obtain high-performance material distributions from initially given material distributions in a given design domain. Its basic idea is to iterate the following processes: (i) selecting material distributions from a dataset of material distributions according to eliteness, (ii) generating new material distributions using a deep generative model trained with the selected elite material distributions, and (iii) merging the generated material distributions with the dataset. Because of the nature of a deep generative model, the generated material distributions are diverse and inherit features of the training data, that is, the elite material distributions. Therefore, it is expected that some of the generated material distributions are superior to the current elite material distributions, and by merging the generated material distributions with the dataset, the performances of the newly selected elite material distributions are improved. The performances are further improved by iterating the above processes. The usefulness of data-driven topology design is demonstrated through numerical examples., Comment: 25 pages, 25 figures

Topology optimization is a powerful methodology for generating novel designs with a high degree of design freedom. In exchange for this attractive feature, topology optimization cannot generally avoid multimodality, which often impedes finding a satisfactory solution when dealing with strongly nonlinear optimization problems. In this study, we focus on constructing a framework that aims to indirectly solve such complex topology optimization problems. The framework is based on multifidelity topology design (MFTD), the basic concept of which is to divide solving an original topology optimization problem into two kinds of procedures, i.e., low-fidelity optimization and high-fidelity evaluation. We build the framework as a data-driven approach, where the design candidates given by solving the low-fidelity optimization problem are iteratively updated based on the idea of the evolutionary algorithm (EA). As a key procedure to realize a crossover-like operation in the high-dimensional design space, a variational autoencoder—one of the representative deep generative models—is utilized for generating a new dataset composed of various material distributions. Besides, we propose a mutation-like operation for generating novel material distributions based on reference ones in the dataset. By integrating these operations with an elitism-based selection procedure, we propose data-driven MFTD that enables gradient-free optimization even if tackling a complex optimization problem with a high degree of design freedom. We apply the proposed framework to forced convection heat transfer problems, where the low-fidelity optimization problem is formulated using a Darcy flow model, whereas the high-fidelity evaluation is conducted using a Navier–Stokes model. We first demonstrate that the obtained results from the proposed framework can achieve almost identical performance compared with that of the directly solved results in a well-known 2D laminar heat transfer problem. We then show that the proposed framework can find solutions in minimax problems of topology optimization pertaining to 3D laminar and turbulent heat transfer.

Whereas topology optimization has achieved immense success, it involves an intrinsic difficulty. That is, optimized structures obtained by topology optimization strongly depend on the settings of the objective and constraint functions, i.e., the formulation. Nevertheless, the appropriate formulation is not usually obvious when considering structural design problems. Although trial-and-error to determine appropriate formulations are implicitly performed in several studies on topology optimization, it is important to explicitly support the process of trial-and-error. Therefore, in this study, we propose a new framework for topology optimization to determine appropriate formulations. The basic idea of this framework is incorporating knowledge discovery in databases (KDD) and topology optimization. Thus, we construct a database by collecting various and numerous material distributions that are obtained by solving various structural design problems with topology optimization, and find useful knowledge with respect to appropriate formulations from the database on the basis of KDD. An issue must be resolved when realizing the above idea, namely the material distribution in the design domain of a data record must be converted to conform to the design domain of the target design problem wherein an appropriate formulation should be determined. For this purpose, we also propose a material distribution-converting method termed as design domain mapping (DDM). Several numerical examples are used to demonstrate that the proposed framework including DDM successfully and explicitly supports the process of trial-and-error to determine the appropriate formulation.

It has previously been confirmed that Kuril harbor seals Phoca vitulina stejnegeri cause damage to the chum salmon Oncorhynchus keta setnet fishery along the east coast of Hokkaido, Japan, but the level of damage has increased markedly with the recovery of their population in recent years. In this study, we attached an optical camera (Trawl Camera) and a dual-frequency identification sonar (DIDSON) acoustic camera to a setnet to observe the behavior of seals as they invaded the setnet, and to determine the number of salmon inside the net, to help inform the development of modified fishing gear. Salmon were observed at all times during daytime with the Trawl Camera, while seals were only observed once. Observations using the DIDSON in its low-frequency mode confirmed that the behavior of seals became vigorous from around sunset to nighttime within the recording time (1530–2100 hours). Observations using the DIDSON high-frequency mode showed that the overall lengths and body widths of seals ranged from 1.0 to 1.6 m and 0.15 to 0.35 m, respectively, while their swimming speeds ranged from 0.4 to 2.6 m/s, increasing around sunset and declining into the night. These results imply that seals mainly invade the setnet from evening to nighttime to predate on salmon.

Elucidation of the mechanism by which the shape of bones is formed is essential for understanding vertebrate development. Bones support the body of vertebrates by withstanding external loads, such as those imposed by gravity and muscle tension. Many studies have reported that bone formation varies in response to external loads. An increased external load induces bone synthesis, whereas a decreased external load induces bone resorption. This relationship led to the hypothesis that bone shape adapts to external load. In fact, by simulating this relationship through topology optimization, the internal trabecular structure of bones can be successfully reproduced, thereby facilitating the study of bone diseases. In contrast, there have been few attempts to simulate the external structure of bones, which determines vertebrate morphology. However, the external shape of bones may be reproduced through topology optimization because cells of the same type form both the internal and external structures of bones. Here, we constructed a three-dimensional topology optimization model to attempt the reproduction of the external shape of teleost vertebrae. In teleosts, the internal structure of the vertebral bodies is invariable, exhibiting an hourglass shape, whereas the lateral structure supporting the internal structure differs among species. Based on the anatomical observations, we applied different external loads to the hourglass-shaped part. The simulations produced a variety of three-dimensional structures, some of which exhibited several structural features similar to those of actual teleost vertebrae. In addition, by adjusting the geometric parameters, such as the width of the hourglass shape, we reproduced the variation in the teleost vertebrae shapes. These results suggest that a simulation using topology optimization can successfully reproduce the external shapes of teleost vertebrae. By applying our topology optimization model to various bones of vertebrates, we can understand how the external shape of bones adapts to external loads., Author summary In this paper, we developed a computational method to investigate the relationship between three-dimensional bone shape and external loads imposed on bones. Many studies report that bone formation varies in response to external loads. An increased external load induces bone synthesis, whereas a decreased external load induces bone resorption. This relationship led to the hypothesis that the shape of bones adapts to external load. However, it remains unclear whether this hypothesis can explain the shape of bones. Here, we constructed a three-dimensional mathematical model that imitates the cellular activities of bone formation to attempt the reproduction of the shape of teleost vertebrae. In teleosts, the shape of the vertebrae differs among the species. We set the multiple types of external load conditions in the simulations and compared the simulation results with different teleost vertebrae. The produced structures that can resist the deformation of the surrounding tissues exhibited multiple structural features similar to the vertebrae of several teleost species. This result shows that the formation of bone shape can be explained by the adaptation to external load.

The sediments of shallow marine waters and lakes around Antarctica provide valuable records of sea-level changes. Understanding the timing and amplitude of Antarctic Ice Sheet changes during the last deglaciation is essential to assess the effect of glacial isostatic adjustments on the present ice-sheet mass balance. However, the difficulty in accessing Antarctica makes it challenging to obtain field-based evidence of ice-sheet and sea-level change during the last deglaciation. We used a portable sonar system to measure bathymetry and water column profiles (sea temperature, salinity, dissolved oxygen, and turbidity) in Lake Nurume and shallow marine waters of Langhovde, East Antarctica, to collect baseline data for sea-level reconstruction from the Last Glacial Maximum (~20 ka). The bathymetry data reveals the surveyed shallow marine waters of Langhovde have basins of 100 m water depth with approximately −67 and −92 m sills, in which sediments provide a potentially useful sea-level archive for the last deglaciation. The water column profile in Lake Nurume reveals a chemocline at ~11 m water depth and anoxic condition below that depth. These baseline data will be useful to reconstruct sea-level and ice-sheet changes in East Antarctica.

Between 1950 and 1980, about half of Yokoshima Island disappeared beneath the East China Sea. The island lies about 1 km off the coast of Nagasaki and was mined for coal during the late 19th and early 20th centuries. We analyzed the geology of the island and surrounding seafloor to investigate how it became submerged. Two low-cost techniques were used to view underwater structures: a commercial drone fitted with a video camera in waters shallower than 5 m and an echo sounder and side-scan sonar system designed for amateur fishers in waters deeper than 5 m. We showed that the partial submergence of the island could be interpreted as a result of subsidence. Subsidence and northward tilting of sedimentary rocks north of the island, probably caused by collapse of abandoned subsea mine workings, created an extensional regime south of the island that led to the formation of steep cliffs and collapse of the southern side of the island. Our study also shows that low-cost commercially available technology can be used for rapid scientific investigations in shallow water areas.

We examined whether AN69ST (acrylonitrile and methallyl sulfonate copolymer) membranes adsorb nafamostat mesilate. This study retrospectively analyzed 87 continuous hemodiafiltration sessions in vivo. We divided the continuous hemodiafiltration sessions into AN69ST and non-AN69ST groups using the nafamostat mesilate dose and activated clotting time as indicators of nafamostat mesilate adsorption onto the membrane. Furthermore, we studied the in vitro adsorption of nafamostat mesilate from nafamostat mesilate solutions onto four different hemodialysis membranes. This in vivo study shows that nafamostat mesilate doses were significantly higher, but activated clotting times were shorter (P < 0.001) in the AN69ST group than in the non-AN69ST group. These results suggest that AN69ST adsorbs nafamostat mesilate. Further, the in vitro experiments show that nafamostat mesilate adsorbs AN69ST on membranes significantly more than the other membranes tested. These in vitro and clinical findings provide evidence that AN69ST may adsorb nafamostat mesilate.

This paper presents topology optimization for the design of flow fields in vanadium redox flow batteries (VRFBs), which are large-scale storage systems for renewable energy resources such as solar and wind power. It is widely known that, in recent VRFB systems, one of the key factors in boosting charging or discharging efficiency is the design of the flow field around carbon fiber electrodes and in flow channels. In this study, topology optimization is applied in order to achieve optimized flow field designs. The optimization problem is formulated as a maximization problem for the generation rate of the vanadium species governed by a simplified electrochemical reaction model. A typical porous model is incorporated into the optimization problem for expressing the carbon fiber electrode; furthermore, a mass transfer coefficient that depends on local velocity is introduced. We investigate the dependencies of the optimized configuration with respect to the porosity of the porous electrode and the pressure loss. Results indicate that patterns of interdigitated flow fields are valid designs for VRFBs.