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Abstract Background As a key determinant of ill-health, family violence is inadequately responded to within Aotearoa New Zealand health policy and practice. Without adequate system support, health professionals can often be unsure of what to do, or how to help. Developed in response to this system gap, ‘Atawhai’ aims to make it easier for primary care professionals to respond to family violence. Methods Underpinned by indigenous Māori customs, Atawhai combines complexity theory and participatory research methodologies to be responsive to the complexity involved in family violence. We worked with 14 primary care professionals across ten whakawhitiwhiti kōrero wānanga (meetings for deliberate dialogue) to identify and develop primary care system pathways and tools for responding to family violence. This paper focuses on the development of Atawhai through wānanga and observation methods. Methods used to capture change will be reported separately. Findings Atawhai is a relational response to family violence, focused on developing a network of trusted relationships between health and social care professionals to support safe responses to those accessing care. This study identified four key health system pathways to responsiveness and developed associated tools to support health care responsiveness to family violence. We found the quality of relationships, both among professionals and with those accessing care, coupled with critical reflection on the systems and structures that shape policy and practice are essential in generating change within primary care settings. Conclusions Atawhai is a unique health care response to family violence evidenced on empirical knowledge of primary care professionals. Our theoretical lens calls attention to parts of the system often obscured by current health care responses to family violence. Atawhai presents an opportunity to develop a grassroots-informed, long-term response to family violence that evolves in response to needs.

Shota Ueda,1 Shinichi Hori,2 Atsushi Hori,2 Kazuhiro Makitani,2 Ke Wan,3 Tetsuo Sonomura1 1Department of Radiology, Wakayama Medical University, Wakayama, Japan; 2Department of Radiology, Institute for Image Guided Therapy, Izumisano City, Osaka, Japan; 3Clinical Study Support Center, Wakayama Medical University Hospital, Wakayama, JapanCorrespondence: Shota Ueda, Department of Radiology, Wakayama Medical University, 811-1, Kimiidera, Wakayama, Japan, Tel/Fax +81-73-441-0605, Email uedaaa@wakayama-med.ac.jpPurpose: To evaluate the efficacy and safety of chemoembolization with drug-eluting microspheres (DEM-TACE) combined with intra-arterial infusion of bevacizumab in patients with unresectable hepatocellular carcinoma (uHCC) and to identify possible prognostic factors.Patients and Methods: Between November 2014 and December 2020, 34 patients underwent DEM-TACE combined with intra-arterial infusion of bevacizumab for Barcelona Clinic Liver Cancer (BCLC) stage B hepatocellular carcinoma (HCC) beyond the Up-to-seven criteria or BCLC stage C HCC. Patients with extrahepatic metastasis or inferior vena cava invasion were excluded. The primary endpoint was overall survival (OS). The secondary endpoints were safety (assessed using Common Terminology Criteria for Adverse Events v5.0), the response rate at 1 month, and the identification of prognostic factors. The median OS was calculated using the Kaplan–Meier method. The response rate was evaluated according to the modified Response Evaluation Criteria in Solid Tumors. Prognostic factors were investigated by univariate and multivariable analysis using the Cox proportional hazards model.Results: The median OS was 13 months. BCLC stage and presence of portal vein invasion were not significantly associated with OS. There were no grade ≥ 3 adverse events. The Child–Pugh class did not decline after treatment in 31 of 34 patients. The overall response rate was 14.2% and the disease control rate was 100%. Significant prognostic factors were alcoholic liver disease, Child–Pugh score of ≥ 8, and microsphere size of 50– 100 μm.Conclusion: DEM-TACE combined with intra-arterial infusion of bevacizumab is safe and effective, and it could be a treatment option for unresectable HCCs.Keywords: bevacizumab, hepatocellular carcinoma, microspheres, transarterial chemoembolization

COVID-19 has caused a significant global disease burden since it was first identified in December 2019; as of May 2024, [greater than or equal to]750 million cases had been confirmed, [...]

The hazardous plasma environment surrounding Earth poses risks to satellites due to internal charging and surface charging effects. Accurate predictions of these risks are crucial for minimizing damage and preparing for system failures of satellites. To forecast the plasma environment, it is essential to know the current state of the system, as the accuracy of the forecast depends on the accuracy of the initial condition of the forecast. In this study, we use data assimilation techniques to combine observational data and model predictions, and present the first global validation of a data-assimilative electron ring current nowcast during a geomagnetic storm. By assimilating measurements from one satellite and validating the results against another satellite in a different magnetic local time sector, we assess the global response and effectiveness of the data assimilation technique for space weather applications. Using this method, we found that the simulation accuracy can be drastically improved at times when observations are available while eliminating almost all of the bias previously present in the model. These findings contribute to the construction of improved operational models in estimating surface charging risks and providing realistic source populations for radiation belt simulations.

The Japanese national guidelines recommend significantly lower doses of carvedilol for heart failure with reduced ejection fraction (HFrEF) management than the US guidelines. Using real-world data, we determined whether initial and target doses of carvedilol in Japanese patients (JPNs) differ from those in US patients (USPs), especially in Asian Americans (ASA) and Caucasians (CA), and investigated differences in outcomes. We collected data from the electronic medical records, including demographics, carvedilol dosing, tolerability, cardiac functional indicators like EF, cardiovascular events including all-cause deaths, and laboratory values from the University of California, San Diego Health and Osaka University. JPNs had significantly lower doses (mg/day) of carvedilol initiation (66 USPs composed of 38 CAs and 28 ASAs, 17.1±16.2; 93 JPNs, 4.3±4.2, p

Abstract Primates must adapt to changing environments by optimizing their behavior to make beneficial choices. At the core of adaptive behavior is the orbitofrontal cortex (OFC) of the brain, which updates choice value through direct experience or knowledge-based inference. Here, we identify distinct neural circuitry underlying these two separate abilities. We designed two behavioral tasks in which two male macaque monkeys updated the values of certain items, either by directly experiencing changes in stimulus-reward associations, or by inferring the value of unexperienced items based on the task’s rules. Chemogenetic silencing of bilateral OFC combined with mathematical model-fitting analysis revealed that monkey OFC is involved in updating item value based on both experience and inference. In vivo imaging of chemogenetic receptors by positron emission tomography allowed us to map projections from the OFC to the rostromedial caudate nucleus (rmCD) and the medial part of the mediodorsal thalamus (MDm). Chemogenetic silencing of the OFC-rmCD pathway impaired experience-based value updating, while silencing the OFC-MDm pathway impaired inference-based value updating. Our results thus demonstrate dissociable contributions of distinct OFC projections to different behavioral strategies, and provide new insights into the neural basis of value-based adaptive decision-making in primates.

Three-dimensional (3D) perfusable organ models, primarily composed of liver cells, are expected as an efficient tool for in vitro cell-based drug screening and development. Various types of hydrogel-based 3D cell culture systems have been developed, but the lack in proper techniques to form vasculature networks in the hydrogel matrices results in inefficient supply of oxygen and nutrition to the cells. Here we propose a facile strategy to creating a perfusable hydrogel-based liver cell culture system. We utilized a bicontinuous dispersion of an aqueous two-phase system, which was composed of polyethylene glycol (PEG)-rich and gelatin methacrylate (GelMA)-rich phases, to produce cell-encapsulating microporous GelMA-based hydrogels. We successfully encapsulated HepG2 cells in the hydrogel matrix with a high cell viability, and confirmed that the spongious hydrogel was superior to homogeneous hydrogels for 3D cell culture. We performed perfusion culture for the cells encapsulated in the hydrogel sponge, to verify the usability and versatility of the presented hydrogel material for perfusion culture. The presented approach would be useful as a unique tool for developing organs-on-a-chip systems.

Abstract Microbial cells serve as efficient and environmentally friendly biocatalysts, but their stability and reusability in practical applications must often be improved through immobilization. Acinetobacter sp. Tol 5 shows high adhesiveness to materials due to its large cell surface protein AtaA, which consists of 3630 amino acids (aa). Previously, we developed a method for immobilizing bacteria using AtaA. Herein, we investigated the cell immobilization ability of in-frame deletion (IFD) mutants of AtaA with different sizes in Tol 5. Mini-AtaA, which consists of 775 aa and is functional in Escherichia coli, was produced and present on the cell surface; however, mini-AtaA showed no immobilization ability in Tol 5. A cell immobilization assay was performed with cells expressing 16 IFD mutants of AtaA with different sizes, revealing that a length of at least 1417 aa was required for the sufficient immobilization of Tol 5 cells; thus, the minimum length needed to achieve the adhesive function of AtaA varies among bacterial species. The constructed mutant library of AtaA ranging from 3630 to 775 aa will allow researchers to quickly and easily explore the optimal size of AtaA, even for bacteria newly introduced to AtaA.

Abstract Stalagmites are useful archives in reconstructing paleoclimates: most paleoclimate studies used stalagmites that are distributed in specific locations and ages. We examined a stalagmite (GYM-1) collected from Nara Prefecture, central Japan, where limestone areas are limited. Applying 238U–234U method, the ages of GYM-1 were determined as 744 ± 70 to 677 ± 74 ka (based only on analytical uncertainties, 1σ). Even assuming a 10% uncertainty in the initial activity of 234U/238U, (234U/238U)0, this age could be still older than 460 ka. Temperatures calculated based on δD in the fluid inclusions and δ18O in the calcium carbonate ranged from 9.0 to 11.9 °C (10.8 ± 0.9 °C on average) or from 6.0 to 9.1 °C (7.9 ± 0.9 °C on average) depending on the equation. The estimated temperature suggests that GYM-1 formed during an interglacial period of the Middle Pleistocene. Synchronous behavior of isotopic values with lamination likely reflects seasonal temperature in a highly ventilated cave system.

Abstract Background Mega-aortic syndrome including aortic arch and descending aortic aneurysm is a challenging surgical case. Because the aorta continuously dilates, creating the distal anastomosis sites becomes an issue. Despite the developments in endovascular techniques including frozen elephant trunk, in the case of mega-aortic syndrome or mycotic aneurysm, extensive surgical repair is still a strong armamentarium. Our patient had a mega-aorta with chronic aortic dissection. Herein, we show tips regarding concurrent ascending, aortic arch, and descending aortic replacement via posterolateral thoracotomy for this relatively young patient. Case presentation A 46-year-old man with chronic kidney disease had chronic type A aortic dissection with an extensively dilated thoracic aorta from the distal ascending to the descending aorta measuring 63 mm in diameter and abdominal aorta measuring 50 mm. The short segment of the distal descending aorta was narrowed to 36 mm. The patient underwent a concurrent replacement of the distal ascending aorta, aortic arch, and descending aorta via a posterolateral thoracotomy. The patient was extubated on postoperative day (POD) 1 and discharged home without serious complications such as stroke, respiratory failure, or renal failure on POD 18. The 1-year follow-up computed tomography did not find issues in the anastomosis sites; however, the abdominal aorta enlarged from 50 to 58 mm. The patient underwent a thoracoabdominal aortic replacement and recovered well without any complications. Conclusions Good exposure and meticulous organ protection methods are key to a safe concurrent replacement of the ascending, aortic arch, and descending aorta via posterolateral thoracotomy.

Abstract Stiff knee gait (SKG) occurrence after a stroke is associated with various abnormal muscle activities; however, the interactions among these muscles are unclear. This study aimed to elucidate the muscle synergy characteristics during walking in patients with SKG after a stroke. This cross-sectional study included 20 patients with poststroke SKG (SKG group), 16 patients without poststroke SKG (non-SKG group), and 15 healthy adults (control group). Participants walked a 10-m distance at a comfortable speed, and electromyographic data were recorded from six lower-limb muscles. Non-negative matrix factorization was employed to derive time-varying activity (C), muscle weights (W), and the percentage of total variance accounted for (tVAF) for muscle synergies. The SKG group showed a higher tVAF than the control group. The initial stance module (including knee extensors) showed increased activity during the swing phase. The initial swing module (including hip flexors and ankle dorsiflexors) exhibited a higher activity during the single-support phase but a lower activity during the swing phase. The synergy structure in patients with SKG after stroke was simplified, with specific abnormalities in synergy activities. SKG may arise from several synergy alterations involving multiple muscles, indicating that approaches focused on controlling individual muscle activities are unsuitable.