Evolution of Multiphase Hot Interstellar Medium in Elliptical Galaxies

We present the results of a variety of simulations concerning the evolution of multiphase (inhomogeneous) hot interstellar medium (ISM) in elliptical galaxies. We assume the gases ejected from stars do not mix globally with the circumferential gas. The ejected gas components evolve separately according to their birth time, position, and origin. We consider cases where supernova remnants (SNRs) mix with local ISM. The components with high metal abundance and/or high density cool and drop out of the hot ISM gas faster than the other components because of their high metal abundance and/or density. This makes the average metal abundance of the hot ISM low. Furthermore, since the metal abundance of mass-loss gas decreases with radius, gas inflow from outer region makes the average metal abundance of the hot ISM smaller than that of mass-loss gas in the inner region. As gas ejection rate of stellar system decreases, mass fraction of mass-loss gas ejected at outer region increases in a galaxy. If the mixing of SNRs is ineffective, our model predicts that observed [Si/Fe] and [Mg/Fe] should decrease towards the galactic center because of strong iron emission by SNRs. In the outer region, where the cooling of time of the ISM is long, the selective cooling is ineffective and most of gas components remain hot. Thus, the metal abundance of the ISM in this region directly reflects that of the gas ejected from stars. Our model shows that supernovae are not effective heating sources in the inner region of elliptical galaxies, because most of the energy released by them radiates. Therefore, cooling flow is established even if the supernova rate is high. Mixing of SNRs with ambient ISM makes the energy transfer between supernova explosion and ambient ISM more effective.Comment: 21 pages (AASTeX), 14 figures, accepted for publication in The Astrophysical Journa

Predictors of Hypotension after Adrenalectomy for Pheochromocytoma

The management of blood pressure is a significant concern for surgeons and anesthesiologists performing adrenalectomy for pheochromocytoma. We evaluated clinical factors in pheochromocytoma patients to identify the predictors of postoperative hypotension. The medical records of patients who underwent adrenalectomy for pheochromocytoma between 2001 and 2017 were retrospectively reviewed and clinical and biochemical data were evaluated. Of 29 patients, 13 patients needed catecholamine support in the perisurgical period while 16 patients did not. There were significant differences in median age, tumor size, and blood pressure drop (maxmin) between the 2 groups (68 vs 53 years old, p=0.045; 50 vs 32 mm diameter, p=0.022; 110 vs 71 mmHg, p=0.015 respectively). In univariate logistic analysis, age > 65.5 years, tumor size > 34.5 mm, urine metanephrine > 0.205 mg/day and urine normetanephrine > 0.665 mg/day were significant predictors of prolonged hypotension requiring postoperative catecholamine support. Tumor size and urine metanephrine and urine normetanephrine levels were correlated with postoperative hypotension. These predictors may help in the safe perioperative management of pheochromocytoma patients treated with adrenalectomy

BUROSUMAB IN TUMOR-INDUCED OSTEOMALACIA

Patients with tumor-induced osteomalacia (TIO), an acquired paraneoplastic condition characterized by osteomalacia due to hypophosphatemia, exhibit a similar clinical picture to those with X-linked hypophosphatemic rickets/osteomalacia (XLH). The human monoclonal anti-fibroblast growth factor 23 (FGF23) antibody burosumab (KRN23) increases serum phosphate and improves bone turnover, fracture healing, pain, and physical function in XLH patients by inhibiting circulating FGF23; thus, burosumab is expected to be an effective treatment for TIO. We report here an interim analysis of a multicenter, open-label, intraindividual dose-adjustment study of burosumab (0.3 to 2.0 mg/kg every 4 weeks) in Japanese and Korean TIO patients. The primary endpoint was the fasting serum phosphate level at each visit. Key secondary endpoints were changes over time in bone biomarkers, pharmacodynamic markers, bone histomorphometric parameters, motor function, and patient-reported outcomes. Safety was assessed based on treatment-emergent adverse events (TEAEs). Thirteen patients received burosumab treatment, of whom 4 underwent bone biopsy. The mean dose after week 112 was approximately 1.0 mg/kg. After the first burosumab administration, mean serum phosphate levels increased and remained above the lower limit of normal and in the normal range from weeks 14 to 112. Bone biomarkers initially increased, reaching maximum values at week 16 or 24, and then gradually decreased. After burosumab treatment, patients were able to walk further (evaluated by the 6-minute walk test), reported decreased pain levels, and showed a tendency toward healing of baseline fractures and pseudofractures. Two patients discontinued, one each due to disease progression and consent withdrawal. Burosumab was generally well tolerated, with no treatment-related TEAEs of grade ≥3 and no treatment-related serious AEs. In conclusion, the interim results of this first study of burosumab to treat TIO patients indicate that this drug has the potential to provide clinical benefit for patients with unresectable tumors. The full study results are eagerly anticipated

Steroids-producing nodules: a two-layered adrenocortical nodular structure as a precursor lesion of cortisol-producing adenoma

コルチゾール産生腫瘍の前駆病変を世界で初めて発見--副腎腫瘍の発生メカニズムの解明と副腎皮質疾患の治療への応用に期--京都大学プレスリリース. 2024-04-03.Background: The human adrenal cortex consists of three functionally and structurally distinct layers; zona glomerulosa, zona fasciculata (zF), and zona reticularis (zR), and produces adrenal steroid hormones in a layer-specific manner; aldosterone, cortisol, and adrenal androgens, respectively. Cortisol-producing adenomas (CPAs) occur mostly as a result of somatic mutations associated with the protein kinase A pathway. However, how CPAs develop after adrenocortical cells acquire genetic mutations, remains poorly understood. Methods: We conducted integrated approaches combining the detailed histopathologic studies with genetic, RNA-sequencing, and spatially resolved transcriptome (SRT) analyses for the adrenal cortices adjacent to human adrenocortical tumours. Findings: Histopathological analysis revealed an adrenocortical nodular structure that exhibits the two-layered zF- and zR-like structure. The nodular structures harbour GNAS somatic mutations, known as a driver mutation of CPAs, and confer cell proliferative and autonomous steroidogenic capacities, which we termed steroids-producing nodules (SPNs). RNA-sequencing coupled with SRT analysis suggests that the expansion of the zF-like structure contributes to the formation of CPAs, whereas the zR-like structure is characterised by a macrophage-mediated immune response. Interpretation: We postulate that CPAs arise from a precursor lesion, SPNs, where two distinct cell populations might contribute differently to adrenocortical tumorigenesis. Our data also provide clues to the molecular mechanisms underlying the layered structures of human adrenocortical tissues. Funding: KAKENHI, The Uehara Memorial Foundation, Daiwa Securities Health Foundation, Kaibara Morikazu Medical Science Promotion Foundation, Secom Science and Technology Foundation, ONO Medical Research Foundation, and Japan Foundation for Applied Enzymology

Feasibility of Laparoscopic Radical Cystectomy in Elderly Patients: A Comparative Analysis of Clinical Outcomes in a Single Institution

Laparoscopic radical cystectomy (LRC) is a standard surgical treatment for muscle-invasive bladder cancer and high-risk non-muscle-invasive bladder cancer. LRC is a less invasive modality than conventional open surgery. Therefore, even elderly patients with invasive bladder cancer may be candidates for LRC. In this study, a comparative analysis of perioperative/oncological outcomes between elderly patients and younger patients who underwent LRC was performed to assess the feasibility of LRC in elderly patients. Sixty-eight consecutive patients who underwent LRC between October 2013 and March 2018 were enrolled and stratified into those younger than 75 years (n=37) and those ≥ 75 years old (n=31). The median follow-up period was 28.2 months. The preoperative and operative parameters and complications were similar in both groups. The 2-year overall survival (OS) was 64.4% in the younger vs. 76.4% in the elderly group (p=0.053), cancer-specific survival (CSS) was 79.3% vs. 81.7% (p=0.187), and recurrence-free survival (RFS) was 58.2% vs. 75.7% (p=0.174), respectively. No significant differences were observed in OS, CSS, or RFS between the groups. No significant differences were found between the groups with respect to peri-surgical/oncological outcomes. We conclude that LRC is feasible in elderly patients

Serum growth differentiation factor 15 is a novel biomarker with high predictive capability for liver cancer occurrence in patients with MASLD regardless of liver fibrosis

Kumazaki S., Hikita H., Tahata Y., et al. Serum growth differentiation factor 15 is a novel biomarker with high predictive capability for liver cancer occurrence in patients with MASLD regardless of liver fibrosis. Alimentary Pharmacology and Therapeutics , (2024); https://doi.org/10.1111/apt.18063.Background and Aims: Although metabolic dysfunction-associated steatotic liver disease (MASLD) patients with a Fib-4 index >1.3 are recommended for fibrosis evaluation via elastography or biopsy, a more convenient method identifying high-risk populations requiring follow-up is needed. We explored the utility of serum levels of growth differentiation factor-15 (GDF15), a cell stress-responsive cytokine related to metabolic syndrome, for stratifying the risk of clinical events in MASLD patients. Methods: Serum GDF15 levels were measured in 518 biopsy-performed MASLD patients, 216 MASLD patients for validation, and 361 health checkup recipients with MASLD. Results: In the biopsy-MASLD cohort, multivariate analysis indicated that the serum GDF15 level was a risk factor for liver cancer, independent of the fibrosis stage or Fib-4 index. Using a GDF15 cutoff of 1.75 ng/mL based on the Youden index, high-GDF15 patients, regardless of fibrosis status, had a higher liver cancer incidence rate. While patients with a Fib-4 index 1.3 developed liver cancer and decompensated liver events at significantly higher rates and had poorer prognoses. In the validation cohort, high-GDF15 patients had significantly higher incidences of liver cancer and decompensated liver events and poorer prognoses than low-GDF15 patients, whether limited to high-Fib-4 patients. Among health checkup recipients with MASLD, 23.0% had a Fib-4 index >1.3, 2.7% had a Fib-4 index >1.3 and >1.75 ng/mL GDF15. Conclusions: Serum GDF15 is a biomarker for liver cancer with high predictive capability and is useful for identifying MASLD patients requiring regular surveillance

粒子ベースのマルチフィジクスな数値シミュレーション手法の土構造物設計への応用と粒状地盤材料のマイクロメカニクス

京都大学0048新制・課程博士博士(農学)甲第19050号農博第2128号新制||農||1032(附属図書館)学位論文||H27||N4932(農学部図書室)32001京都大学大学院農学研究科地域環境科学専攻(主査)教授 村上 章, 教授 藤原 正幸, 教授 澤田 純男学位規則第4条第1項該当Doctor of Agricultural ScienceKyoto UniversityDFA

Group effect on ultimate lateral resistance of piles against uniform ground movement

In earthquake engineering, pile foundations are designed to withstand the lateral loading that results from large displacements due to ground movement caused by strong earthquakes. The distress and failure of superstructures occurs when the lateral load exceeds the ultimate lateral resistance of the piles. The aim of this study is to estimate the ultimate lateral resistance of piles especially in terms of the group effect induced by the pile arrangement. Several experimental and numerical analyses have been conducted on pile groups to investigate the group effect when the groups are subjected to uniform large horizontal ground movement. However, the ultimate lateral resistance of the pile groups in these studies was calculated by applying load to the piles. The present study directly assesses the ultimate lateral resistance of pile groups against ground movement by systematically varying the direction of the ground movement. Although the load bearing ratio of each pile in a pile group, defined as the ratio of the ultimate lateral resistance of each pile in a pile group to that of a single pile, is an important design criterion, it was difficult to assess in past works. This study focuses on the load bearing ratio of each pile against ground movement in various directions. The use of the finite element method (FEM) provides options for simulating the pile-soil system with complex pile arrangements by taking the complicated geometry of the problem into account. The ultimate lateral resistance is examined here for pile groups consisting of a 2 × 2 arrangement of four piles, as well as two piles, three piles, four piles, and an infinite number of piles arranged in a row through case studies in which the pile spacing is changed by applying the two-dimensional rigid plastic finite element method (RPFEM). The RPFEM was extended in this work to calculate not only the total ultimate lateral resistance of pile groups, but also the load bearing ratio of the piles in the group. The obtained results indicate that the load bearing ratio generally increases with an increase in pile spacing and converges to almost unity at a pile spacing ratio of 3.0 with respect to the pile diameter. Moreover, the group effect was further investigated by considering the failure mode of the ground around the piles