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Creatinine clearance (CCr) and pharmacokinetic parameters are markedly affected by pathophysiological changes in patients with sepsis. However, only a few reports have assessed renal function in patients with sepsis using the measured CCr. Further, the administration regimen has not been sufficiently evaluated using a population PK (PPK) model across renal function broad ranges. Therefore, this study was performed to construct a meropenem PPK model for patients with sepsis using the measured CCr and evaluate the optimized meropenem dosing regimen based on the CCr.Patients with sepsis who received intravenous meropenem at the Showa University Hospital were enrolled in this prospective observational study. The PPK model was constructed using blood samples and clinical information of patients. The probability of target attainment (PTA) indicates the likelihood of achieving 50% time above the minimum inhibitory concentration (%TMIC) based on 10,000 virtual patients using Monte Carlo simulations. The PTA for each meropenem regimen was 50% TMIC based on different renal functions using the Monte Carlo simulation.One hundred samples were collected from 31 patients. The final PPK model incorporating the measured CCr as a covariate in CL displayed the best fit. The recommended dosing regimen to achieve a PTA of 50% TMIC of 4 µg/mL was 1 g every 8 h as a 3 h prolonged infusion for patients with CCr 85-130 mL/min and 1 g every 8 h as an 8 h continuous infusion for patients with CCr ≥ 130 mL/min.This model precisely predicted meropenem concentrations in patients with sepsis by accurately evaluating renal function using the measured CCr. Extended dosing was demonstrated to be necessary to achieve a PTA of 50% TMIC for patients with CCr ≥ 85 mL/min. Meropenem effectiveness can be maximized in patients with sepsis by selecting the appropriate dosing regimen based on renal function and the MIC.

Small flares frequently occur in the quiet Sun. Previous studies have noted that they share many common characteristics with typical solar flares in active regions. However, their similarities and differences are not fully understood, especially their thermal properties. In this study, we performed imaging spectroscopic observations in the H$\alpha$ line taken with the Solar Dynamics Doppler Imager on the Solar Magnetic Activity Research Telescope (SMART/SDDI) at the Hida Observatory and imaging observations with the Atmospheric Imaging Assembly onboard Solar Dynamics Observatory (SDO/AIA). We analysed 25 cases of small flares in the quiet Sun over the thermal energy range of $10^{24}-10^{27}\,\mathrm{erg}$, paying particular attention to their thermal properties. Our main results are as follows: (1) We observe a redshift together with line centre brightening in the H$\alpha$ line associated with more than half of the small flares. (2) We employ differential emission measure analysis using AIA multi-temperature (channel) observations to obtain the emission measure and temperature of the small flares. The results are consistent with the Shibata & Yokoyama (1999, 2002) scaling law. From the scaling law, we estimated the coronal magnetic field strength of small flares to be 5 --15 G. (3) The temporal evolution of the temperature and the density shows that the temperature peaks precede the density peaks in more than half of the events. These results suggest that chromospheric evaporations/condensations play an essential role in the thermal properties of some of the small flares in the quiet Sun, as does for large flares., Comment: 14 pages, 12 figures, accepted for publication in MNRAS

Energy-generating and storage systems, such as photovoltaic (PV) panels and energy storage batteries in homes, are becoming increasingly popular in the context of decarbonization. The systems are also expected to increase household resilience to natural hazard-triggered blackouts. However, how these systems contribute to the use of electrical appliances in households in actual cases is not sufficiently known. Therefore, this report aims to describe the activities that a household with an energy-generating and storage system could undertake during a natural hazard-triggered blackout. We focused on the blackout triggered by the 2018 Hokkaido Eastern Iburi Earthquake (approximately 2.95 million households lost power) and conducted an interview with a household living in a detached all-electric house with a PV and battery system. The results showed that the household lived without inconveniences during the blackout due to the power supply from the installed system, despite the weather. They charged cell phones and used a television, refrigerator, microwave oven, cooking heater, and bath. Moreover, the household’s electricity was also supplied to other households. These results clarified the actual benefit of enhancing household and community resilience of the systems. The results will aid household decision-making for the installation and governmental consideration of subsidies.

Cardiac surgery is performed worldwide. Most types of cardiac surgery are performed using cardiopulmonary bypass (CPB). Cardiac surgery performed with CPB is associated with morbidities. CPB needs an extracorporeal circulation that replaces the heart and lungs, and performs circulation, ventilation, and oxygenation of the blood. The lower limit of mean blood pressure to maintain blood flow to vital organs increases in people with chronic hypertension. Because people undergoing cardiac surgery commonly have chronic hypertension, we hypothesised that maintaining a relatively high blood pressure improves desirable outcomes among the people undergoing cardiac surgery with CPB.To evaluate the benefits and harms of higher versus lower blood pressure targets during cardiac surgery with CPB.We used standard, extensive Cochrane search methods. The latest search of databases was November 2021 and trials registries in January 2020.We included randomised controlled trials (RCTs) comparing a higher blood pressure target (mean arterial pressure 65 mmHg or greater) with a lower blood pressure target (mean arterial pressure less than 65 mmHg) in adults undergoing cardiac surgery with CPB.We used standard Cochrane methods. Primary outcomes were 1. acute kidney injury, 2. cognitive deterioration, and 3. all-cause mortality. Secondary outcomes were 4. quality of life, 5. acute ischaemic stroke, 6. haemorrhagic stroke, 7. length of hospital stay, 8. renal replacement therapy, 9. delirium, 10. perioperative transfusion of blood products, and 11. perioperative myocardial infarction. We used GRADE to assess certainty of evidence.We included three RCTs with 737 people compared a higher blood pressure target with a lower blood pressure target during cardiac surgery with CPB. A high blood pressure target may result in little to no difference in acute kidney injury (risk ratio (RR) 1.30, 95% confidence interval (CI) 0.81 to 2.08; I² = 72%; 2 studies, 487 participants; low-certainty evidence), cognitive deterioration (RR 0.82, 95% CI 0.45 to 1.50; I² = 0%; 2 studies, 389 participants; low-certainty evidence), and all-cause mortality (RR 1.33, 95% CI 0.30 to 5.90; I² = 49%; 3 studies, 737 participants; low-certainty evidence). No study reported haemorrhagic stroke. Although a high blood pressure target may increase the length of hospital stay slightly, we found no differences between a higher and a lower blood pressure target for the other secondary outcomes. We also identified one ongoing RCT which is comparing a higher versus a lower blood pressure target among the people who undergo cardiac surgery with CPB.A high blood pressure target may result in little to no difference in patient outcomes including acute kidney injury and mortality. Given the wide CIs, further studies are needed to confirm the efficacy of a higher blood pressure target among those who undergo cardiac surgery with CPB.

Gamma oscillations are thought to play a role in information processing in the brain. Bursting neurons, which exhibit periodic clusters of spiking activity, are a type of neuron that are thought to contribute largely to gamma oscillations. However, little is known about how the properties of bursting neurons affect the emergence of gamma oscillation, its waveforms, and its synchronized characteristics, especially when subjected to stochastic fluctuations. In this study, we proposed a bursting neuron model that can analyze the bursting ratio and the phase response function. Then we theoretically analyzed the neuronal population dynamics composed of bursting excitatory neurons, mixed with inhibitory neurons. The bifurcation analysis of the equivalent Fokker-Planck equation exhibits three types of gamma oscillations of unimodal firing, bimodal firing in the inhibitory population, and bimodal firing in the excitatory population under different interaction strengths. The analyses of the macroscopic phase response function by the adjoint method of the Fokker-Planck equation revealed that the inhibitory doublet facilitates synchronization of the high-frequency oscillations. When we keep the strength of interactions constant, decreasing the bursting ratio of the individual neurons increases the relative high-gamma component of the populational phase-coupling functions. This also improves the ability of the neuronal population model to synchronize with faster oscillatory input. The analytical frameworks in this study provide insight into nontrivial dynamics of the population of bursting neurons, which further suggest that bursting neurons have an important role in rhythmic activities.

Kepler showed a paucity of planets with radii of 1.5–2 R⊕ around solar mass stars but this radius-gap has not been well studied for low-mass star planets. Energy-driven escape models like photoevaporation and core-powered mass-loss predict opposing transition regimes between rocky and non-rocky planets when compared to models depicting planets forming in gas-poor environments. Here, we present transit observations of three super-Earth sized planets in the radius-gap around low-mass stars using high-dispersion InfraRed Doppler spectrograph on the Subaru 8.2 m telescope. The planets GJ 9827 b and d orbit around a K6V star and TOI-1235 b orbits a M0.5 star. We limit any planet-related absorption in the 1083.3 nm lines of triplet He i by placing an upper-limit on the equivalent width of 14.71, 18.39, and 1.44 mÅ for GJ 9827 b (99 per cent confidence), GJ 9827 d (99 per cent confidence), and TOI-1235 b (95 per cent confidence), respectively. Using a Parker wind model, we cap the mass-loss at >0.25 M⊕ Gyr−1 and >0.2 M⊕ Gyr−1 for GJ 9827 b and d, respectively (99 per cent confidence), and >0.05 M⊕ Gyr−1 for TOI-1235 b (95 per cent confidence) for a representative wind temperature of 5000 K. Our observed results for the three planets are more consistent with the predictions from photoevaporation and/or core-powered mass-loss models than the gas-poor formation models. However, more planets in the radius-gap regime around the low-mass stars are needed to robustly predict the atmospheric evolution in planets around low-mass stars.

Background It is unclear whether hepatocyte function and/or portal hypertension improves if a sustained virologic response (SVR) is achieved with direct-acting antivirals in patients with decompensated hepatitis C-related cirrhosis. Methods We examined the safety and efficacy of a 12-week course of sofosbuvir/velpatasvir (SOF/VEL) in 20 patients with decompensated hepatitis C-related cirrhosis. We also investigated changes in the hepatocyte receptor index (LHL15) and blood clearance index (HH15) by Tc-99 m-galactosyl human serum albumin scintigraphy, liver stiffness measurement (LSM) by transient elastography, and hepatic venous pressure gradient (HVPG) in patients who achieved an SVR at 24 weeks after treatment (SVR24). Results One patient discontinued treatment because of rectal variceal hemorrhage, and 19 patients completed treatment. SVR24 was achieved in 17 patients (89%). Median LHL15 increased from 0.72 pre-treatment to 0.82 after SVR24 (p = 0.012), and median HH15 decreased from 0.82 pre-treatment to 0.76 after SVR24 (p = 0.010). The percentage of patients with LSM ≥ 20 kPa was 90% before treatment and remained at 90% after SVR24. However, the percentage with severe portal hypertension (defined as HVPG ≥ 12 mmHg) decreased from 92% pre-treatment to 58% after SVR24 (p = 0.046). Patients with a decreased HVPG from pre-treatment to after SVR24 had a smaller pre-treatment spleen volume than those with an increased HVPG (median, 252 vs. 537 mL, p = 0.028). Conclusion Achieving SVR24 with SOF/VEL treatment in patients with decompensated hepatitis C-related cirrhosis can be expected to improve hepatocyte function and portal hypertension on short-term follow-up.

OBJECTIVE Various complications have been reported in the treatment of pediatric spinal deformities. Among these, instrument-related complications could be critical concerns and risks of reoperation. This study aimed to identify the incidence and causes of complications after primary definitive fusion for pediatric spine deformities. METHODS The authors retrospectively collected data from 14 institutions about patients who underwent primary definitive fusion between 2015 and 2017. There were 1490 eligible patients (1184 female and 306 male), with a mean age of 13.9 years. The incidence, causes, and reoperation rates were analyzed according to 4 etiologies of pediatric spine deformity (congenital, neuromuscular, syndromic, idiopathic). The complications were also categorized as screw-, hook-, or rod-related complications, implant loosening or backout, and junctional problems. RESULTS The incidence of overall instrument-related complications was 5.6% (84 cases). Regarding etiology, the incidence rates were 4.3% (idiopathic), 6.8% (syndromic), 7.9% (congenital), and 10.4% (neuromuscular) (p < 0.05). The most common causes were pedicle screw malposition (60.7%), followed by implant backout or loosening (15.4%), junctional problems (13.1%), rod breakage (4.8%), and other complications (6.0%). Univariate analysis showed that etiology, type of deformity (kyphosis), surgical procedure, operation time, and estimated blood loss were significant factors. Multivariate analysis revealed that etiology (neuromuscular), surgical procedure (combined approach), and operation time (> 5 hours) remained as significant risk factors. Among all patients with instrument-related complications, 45% (38/84) required revision surgery. Of these cases, > 50% were related to pedicle screw malposition. Medial breach was the most common complication regardless of location, from upper thoracic to lumbar spine. CONCLUSIONS Pedicle screw malposition was the primary cause of overall complications and subsequent reoperation. In addition to more precise screw insertion techniques, meticulous confirmation of pedicle screw placement, especially of medial breach, may reduce the overall instrument-related complications and revision rates.

Despite standard-of-care treatment, more than 30% of patients with resectable colorectal cancer (CRC) relapse. Circulating tumor DNA (ctDNA) analysis may enable postsurgical risk stratification and adjuvant chemotherapy (ACT) treatment decision-making. We report results from GALAXY, which is an observational arm of the ongoing CIRCULATE-Japan study (UMIN000039205) that analyzed presurgical and postsurgical ctDNA in patients with stage II–IV resectable CRC (n = 1,039). In this cohort, with a median follow-up of 16.74 months (range 0.49–24.83 months), postsurgical ctDNA positivity (at 4 weeks after surgery) was associated with higher recurrence risk (hazard ratio (HR) 10.0, P P P

A robust network structure of single-molecule magnets that exhibits perpendicular magnetic anisotropy preferred for memory devices was constructed utilizing coordination chemistry at the air–liquid interface.

Design and synthesis of MKN-3 derivatives: a new class of small molecules, MKN-3 derivatives, were developed based on in silico screening, as dipeptide mimics of Trp184 and Met185 at the hydrophobic interaction site between two capsid (CA) proteins.

In a Rh/CrOx core–shell cocatalyst for water-splitting photocatalysts, CrOx serves as an electron pathway, transfers the photoexcited electrons from photocatalysts to Rh (reduction site), and improves the H2 evolution activity.

Cancer and Cardiovascular Disease (CVD) are the most common causes of death and disability in many countries. Cancer and CVD are closely related in terms of both scientific and clinical perspectives. Oncocardiology has recently gained attention by oncologists, cardiologists, and radiologists for mutual work on pathophysiology analysis and treatment strategy [1-3]. In various clinical settings, these specialists may collaborate in the diagnosis and treatment of cancer patients with cardiovascular disease.

We report a search for excess absorption in the 1083.2 nm line of ortho (triplet) helium during transits of TOI-1807b and TOI-2076b, 1.25 and 2.5R$_{\rm Earth}$ planets on 0.55- and 10.4-day orbits around nearby $\sim$200~Myr-old K dwarf stars. We limit the equivalent width of any transit-associated absorption to $, Accepted to MNRAS

Fluorescence probes are widely used to assess the molecular environment based on their photo-physical properties. Specifically, flexible and aromatic photo-functional system (FLAP) is unique viscosity probe owing to the excited-state planarization of anthracene wings. We have previously applied fluorescence spectroscopy to monitor the evaporative crystallization of solvents. The fluorescence color and spectral changes, which depend on the aggregation form, enable direct fluorescence visualization during evaporative crystallization. The fluorescence visualization of the liquid-like cluster intermediate proposed in the two-step nucleation model for the nucleation process has been achieved. However, the physical properties of these clusters, especially the viscosity, molecular motion, and intermolecular interactions, are still unclear. In this study, FLAPs are used as probes for local-viscosity changes and space limitations of the liquid-like cluster state during evaporative crystallization by observing the fluorescence-spectral changes and using hyperspectral-camera (HSC) imaging. Green emission originates from the monomer in the solution owing to the free-flapping motion. The fluorescence color turns blue with increasing viscosity under crowding conditions. If the survival time of the liquid-like cluster state is sufficient, crystalline phase (R-phase) formation proceeds via a 2-fold π-stacked array of the V-shaped molecules. It is difficult to form the V-shaped stacked columnar structures in the liquid-like cluster state region, resulting in the deposition of head-to-tail dimer structures, such as the yellow-emissive phase (Y-phase). In the case of the FLAP, the stacking intermediate does not form during solvent evaporation in the liquid-like cluster; rather, it is deposited in an amorphous form that exhibits blue emission (B-phase). These findings suggest that it is important to the maintenance of the survival time of the liquid-like cluster states to organize and rearrange the stacking forms. We have achieved the fluorescence probing of viscosity changes at local molecular motion with solvent depletion during solvent evaporation for the first time.

Impaired high-density lipoprotein (HDL) function is a risk factor for cardiac mortality. We aimed to investigate the association between oxidized HDL (oxHDL) and pericoronary adipose tissue (PCAT) attenuation, a novel imaging biomarker of pericoronary inflammation, by using coronary computed tomography angiography (CTA).A total of 287 outpatients with suspected coronary artery disease who had undergone both oxHDL measurement and coronary CTA were examined. PCAT attenuation values were assessed at the proximal 10-50 mm segments of the right coronary artery on coronary CTA. The presence of significant stenosis (luminal narrowing of50 %) and high-risk plaque characteristics were also evaluated. Patients were then classified into tertiles according to their oxHDL level: low (n = 95), moderate (n = 96), and high (n = 96) groups.PCAT attenuation in the high oxHDL group was significantly higher than that in other groups after adjusting for age and apolipoprotein-A-I. Multivariate linear regression analysis revealed that oxHDL was significantly associated with PCAT attenuation in the right coronary artery (β = 3.832, p 0.001), whereas HDL cholesterol was not. Furthermore, subgroup analyses demonstrated that the association between oxHDL and PCAT attenuation remained significant in older patients (β = 6.367, p 0.001) and in those with hypertension (β = 4.922, p 0.011), dyslipidemia (β = 3.264, p = 0.010), diabetes mellitus (β = 4.284, p = 0.015), and significant stenosis (β = 3.075, p = 0.021).High oxHDL levels were significantly associated with increased pericoronary inflammation, as assessed using coronary CTA. Our results may explain the association between impaired HDL function and the development of coronary atherosclerosis.