Pharmacokinetics of Edoxaban 15 mg in Very Elderly Patients with Nonvalvular Atrial Fibrillation: A Subanalysis of the ELDERCARE-AF Study.

BACKGROUND: We evaluated the pharmacokinetics (PK) of low-dose (15 mg) edoxaban in very elderly patients (≥80 years) with nonvalvular atrial fibrillation (NVAF) and high bleeding risk. METHODS: This subanalysis of the phase 3, randomized, double-blind, placebo-controlled, multicenter ELDERCARE-AF study evaluated edoxaban plasma concentrations and compared them with the Japanese population of the ENGAGE AF-TIMI 48 and Japanese severe renal impairment (SRI) studies. RESULTS: The PK analysis population included 451 patients, 53.8% of whom concomitantly used antiplatelet drugs, 41.0% had SRI, and 38.0% had low body weight. Edoxaban plasma concentrations at trough and 1 to 3 hours post-dose in ELDERCARE-AF were 17.3 ± 13.9 (n = 427) and 93.3 ± 57.8 ng/mL (n = 447), respectively. These values were slightly higher than the 15 mg group in ENGAGE AF-TIMI 48 (n = 79; 12.4 ± 12.1 and n = 115; 78.7 ± 45.0 ng/mL, respectively), lower than the ENGAGE AF-TIMI 48 high-dose reduced to 30 mg group (n = 83; 25.1 ± 36.6 and n = 111; 150 ± 91.6 ng/mL, respectively), but similar to the Japanese SRI study (n = 39; 18.4 ± 11.2 and n = 40; 96.8 ± 48.3 ng/mL, respectively). ELDERCARE-AF patients with SRI and low body weight (≤45 kg) had higher concentrations than those without, and those taking antiplatelet drugs had lower concentrations than those who were not. CONCLUSION: PK data support edoxaban 15 mg once daily for very elderly NVAF patients with high bleeding risk, with caution for patients with SRI and/or low body weight.

Giant nanomechanical energy storage capacity in twisted single-walled carbon nanotube ropes.

A sustainable society requires high-energy storage devices characterized by lightness, compactness, a long life and superior safety, surpassing current battery and supercapacitor technologies. Single-walled carbon nanotubes (SWCNTs), which typically exhibit great toughness, have emerged as promising candidates for innovative energy storage solutions. Here we produced SWCNT ropes wrapped in thermoplastic polyurethane elastomers, and demonstrated experimentally that a twisted rope composed of these SWCNTs possesses the remarkable ability to reversibly store nanomechanical energy. Notably, the gravimetric energy density of these twisted ropes reaches up to 2.1 MJ kg-1, exceeding the energy storage capacity of mechanical steel springs by over four orders of magnitude and surpassing advanced lithium-ion batteries by a factor of three. In contrast to chemical and electrochemical energy carriers, the nanomechanical energy stored in a twisted SWCNT rope is safe even in hostile environments. This energy does not deplete over time and is accessible at temperatures ranging from -60 to +100 °C.

Aqueductal developmental venous anomaly causing obstructive hydrocephalus: A case report and review of the literature.

A developmental venous anomaly (DVA) is a venous drainage of the associated parenchyma that is normally asymptomatic. However, a DVA located adjacent to the aqueduct can cause obstructive hydrocephalus by blocking the flow of cerebrospinal fluid. We describe a rare case of obstructive hydrocephalus due to aqueductal stenosis secondary to a DVA. A 43-year-old man presented with sudden bilateral temporal pain during weight training. Using a 3-Tesla scanner, cranial magnetic resonance imaging (MRI) was performed, and hydrocephalus was found with mild enlargement of the lateral and third ventricles. Susceptibility-weighted imaging and postcontrast MRI revealed that the DVA from the bilateral thalami narrowed the orifice of the aqueduct on its drainage route towards the vein of Galen. We assumed that force exerted during weight training may have caused dilation of the anomalous veins, leading to his symptom. A review of the relevant English-language literature yielded only 19 cases of aqueductal stenosis due to DVA. In comparison to these cases, the duration of symptom in our case was extremely short because the patient had a history of ventriculomegaly detected on plain computed tomography and was diagnosed quickly based on the characteristic finding of DVA: the caput medusae appearance.

Efficacy and Safety of Low-Dose Edoxaban by Body Weight in Very Elderly Patients With Atrial Fibrillation: A Subanalysis of the Randomized ELDERCARE-AF Trial.

BACKGROUND: The ELDERCARE-AF trial showed that low-dose edoxaban benefits elderly patients with nonvalvular atrial fibrillation considered ineligible for standard oral anticoagulants due to high bleeding risk, but whether this applied to patients with extremely low body weight was unclear. METHODS AND RESULTS: This was a prespecified subanalysis by body weight (≤45, >45 kg) of the phase 3, multicenter, randomized, double-blind, placebo-controlled, event-driven ELDERCARE-AF trial, which compared low-dose edoxaban (15 mg once daily) with placebo in Japanese patients considered ineligible for oral anticoagulants at the recommended therapeutic strength or the approved doses. The primary efficacy and safety end points were stroke or systemic embolism and major bleeding (International Society on Thrombosis and Hemostasis definition), respectively. The ≤45-kg weight group included 374/984 patients (38.0%), and the >45-kg group included 610/984 patients (62.0%). The stroke or systemic embolism rate was lower with edoxaban than placebo in both weight groups (≤45 kg: hazard ratio [HR], 0.36 [95% CI, 0.16-0.80]; >45 kg: HR, 0.31 [95% CI, 0.13-0.73]; interaction P=0.82). Major bleeding incidence was numerically higher with edoxaban than placebo (≤45 kg: HR, 3.05 [95% CI, 0.84-11.11]; >45 kg: HR, 1.40 [95% CI, 0.56-3.48), with no interaction with body weight (interaction P=0.33). All-cause mortality was higher in the ≤45-kg group, with no significant difference between treatment groups. CONCLUSIONS: The benefit of edoxaban 15 mg was consistent in elderly patients with atrial fibrillation and extremely low body weight, though clinicians must remain vigilant about the risk of major bleeding, especially gastrointestinal bleeding. REGISTRATION INFORMATION: ClinicalTrials.gov. Identifier: NCT02801669.

Accelerated preprocessing of large numbers of brain images by parallel computing on supercomputers.

"Preprocessing" is the first step required in brain image analysis that improves the overall quality and reliability of the results. However, it is computationally demanding and time-consuming, particularly to handle and parcellate complicatedly folded cortical ribbons of the human brain. In this study, we aimed to shorten the analysis time for data preprocessing of 1410 brain images simultaneously on one of the world's highest-performing supercomputers, "Fugaku." The FreeSurfer was used as a benchmark preprocessing software for cortical surface reconstruction. All the brain images were processed simultaneously and successfully analyzed in a calculation time of 17.33 h. This result indicates that using a supercomputer for brain image preprocessing allows big data analysis to be completed shortly and flexibly, thus suggesting the possibility of supercomputers being used for expanding large data analysis and parameter optimization of preprocessing in the future.

Traveling Subject-Informed Harmonization Increases Reliability of Brain Diffusion Tensor and Neurite Mapping.

Diffusion-weighted magnetic resonance imaging (dMRI) of brain has helped elucidate the microstructural changes of psychiatric and neurodegenerative disorders. Inconsistency between MRI models has hampered clinical application of dMRI-based metrics. Using harmonized dMRI data of 300 scans from 69 traveling subjects (TS) scanning the same individuals at multiple conditions with 13 MRI models and 2 protocols, the widely-used metrics such as diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI) were evaluated before and after harmonization with a combined association test (ComBat) or TS-based general linear model (TS-GLM). Results showed that both ComBat and TS-GLM significantly reduced the effects of the MRI site, model, and protocol for diffusion metrics while maintaining the intersubject biological effects. The harmonization power of TS-GLM based on TS data model is more powerful than that of ComBat. In conclusion, our research demonstrated that although ComBat and TS-GLM harmonization approaches were effective at reducing the scanner effects of the site, model, and protocol for DTI and NODDI metrics in WM, they exhibited high retainability of biological effects. Therefore, we suggest that, after harmonizing DTI and NODDI metrics, a multisite study with large cohorts can accurately detect small pathological changes by retaining pathological effects.

Identifying and reverting the adverse effects of white matter hyperintensities on cortical surface analyses.

The Human Connectome Project (HCP)-style surface-based brain MRI analysis is a powerful technique that allows precise mapping of the cerebral cortex. However, the strength of its surface-based analysis has not yet been tested in the older population that often presents with white matter hyperintensities (WMHs) on T2-weighted (T2w) MRI (hypointensities on T1w MRI). We investigated T1-weighted (T1w) and T2w structural MRI in 43 healthy middle-aged to old participants. Juxtacortical WMHs were often misclassified by the default HCP pipeline as parts of the gray matter in T1w MRI, leading to incorrect estimation of the cortical surfaces and cortical metrics. To revert the adverse effects of juxtacortical WMHs, we incorporated the Brain Intensity AbNormality Classification Algorithm into the HCP pipeline (proposed pipeline). Blinded radiologists performed stereological quality control (QC) and found a decrease in the estimation errors in the proposed pipeline. The superior performance of the proposed pipeline was confirmed using an originally-developed automated surface QC based on a large database. Here we showed the detrimental effects of juxtacortical WMHs for estimating cortical surfaces and related metrics and proposed a possible solution for this problem. The present knowledge and methodology should help researchers identify adequate cortical surface biomarkers for aging and age-related neuropsychiatric disorders.

Vanillin Production Pathways in Alkaline Nitrobenzene Oxidation of Guaiacylglycerol-ß-guaiacyl Ether.

Alkaline nitrobenzene oxidation (AN oxidation) is a significant method for chemical analysis of lignin. Despite its importance in lignin chemistry, the detailed chemical reactions involved in AN oxidation are not yet fully understood. Surprisingly, there is almost no experimentally supported information available regarding the reaction pathways in the AN oxidation of guaiacyl glycerol-ß-guaiacyl ether (GG), a common model compound in lignin chemistry. This study reports the results of our investigation into the formation pathway of vanillin (4-hydroxy-3-methoxybenzaldehyde) in the AN oxidation of GG. Our series of experiments proposed a vanillin formation pathway involving an enol ether with a C2 side chain, 2-methoxy-4-[2-(2-methoxyphenoxy)-ethenyl]-phenol C2EE, as an intermediate, in which C2EE is produced by the non-oxidative degradation of GG by alkali. Another enol ether with a C3 side-chain, Z-4-[3-hydroxy-2-(2-methoxyphenoxy)-1-propen-1-yl]-2-methoxyphenol (C3EE), and the condensation products formed under alkaline conditions were found to be insignificant as vanillin sources. On the other hand, the comparison of the vanillin yields from GG and isolated C2EE (80.7 and 86.5 mol %, respectively) in their AN oxidation to the C2EE yield from GG in the absence of nitrobenzene (69.9 mol %) also suggested that the vanillin formation from GG involved unknown pathways in which C2EE is not an intermediate.

Designed Production of Atomic-Scale Nanowindows in Single-Walled Carbon Nanotubes.

The controlled production of nanowindows in graphene layers is desirable for the development of ultrathin membranes. Herein, we propose a single-atom catalytic oxidation method for introducing nanowindows into the graphene layers of single-walled carbon nanotubes (SWCNTs). Using liquid-phase adsorption, copper(II) 2,3,9,10,16,17,23,24-octakis(octyloxy)-29H,31H-phthalocyanine (CuPc) was adsorbed on SWCNT bundles at a surface coverage of 0.9. Subsequently, narrow nanowindows with a number density of 0.13 nm-2 were produced by oxidation above 550 K, which is higher than the decomposition temperature of bulk CuPc. In particular, oxidation of the CuPc-adsorbed SWCNTs at 623 K increased the surface area from 280 to 1690 m2 g-1 owing to the efficient production of nanowindows. The nanowindow size was estimated to be similar to the molecular size of N2 based on the pronounced low-pressure adsorption hysteresis in the N2 adsorption isotherm. In addition, the enthalpy change for the nanowindow-formation equilibrium decreased by 4 kJ mol-1 when CuPc was present, further evidencing the catalytic effect of the Cu atoms supplied by the adsorbed CuPc molecules.

Cortical adaptation of the night monkey to a nocturnal niche environment: a comparative non-invasive T1w/T2w myelin study.

Night monkeys (Aotus) are the only genus of monkeys within the Simian lineage that successfully occupy a nocturnal environmental niche. Their behavior is supported by their sensory organs' distinctive morphological features; however, little is known about their evolutionary adaptations in sensory regions of the cerebral cortex. Here, we investigate this question by exploring the cortical organization of night monkeys using high-resolution in-vivo brain MRI and comparative cortical-surface T1w/T2w myeloarchitectonic mapping. Our results show that the night monkey cerebral cortex has a qualitatively similar but quantitatively different pattern of cortical myelin compared to the diurnal macaque and marmoset monkeys. T1w/T2w myelin and its gradient allowed us to parcellate high myelin areas, including the middle temporal complex (MT +) and auditory cortex, and a low-myelin area, Brodmann area 7 (BA7) in the three species, despite species differences in cortical convolutions. Relative to the total cortical-surface area, those of MT + and the auditory cortex are significantly larger in night monkeys than diurnal monkeys, whereas area BA7 occupies a similar fraction of the cortical sheet in all three species. We propose that the selective expansion of sensory areas dedicated to visual motion and auditory processing in night monkeys may reflect cortical adaptations to a nocturnal environment.

Effect of Pretreatment Conditions on the Precise Nanoporosity of Graphene Oxide.

Nanoscale pores in graphene oxide (GO) control various important functions. The nanoporosity of GO is sensitive to low-temperature heating. Therefore, it is important to carefully process GO and GO-based materials to achieve superior functions. Optimum pretreatment conditions, such as the pre-evacuation temperature and time, are important during gas adsorption in GO to obtain accurate pore structure information. This study demonstrated that the pre-evacuation temperature and time for gas adsorption in GO must be approximately 333-353 K and 4 h, respectively, to avoid the irreversible alteration of nanoporosity. In situ temperature-dependent Fourier-transform infrared spectra and thermogravimetric analysis-mass spectrometry suggested significant structural changes in GO above the pre-evacuation temperature (353 K) through the desorption of "physically adsorbed water" and decomposition of unstable surface functional groups. The nanoporosity of GO significantly changed above the aforementioned pre-evacuation temperature and time. Thus, standard pretreatment is indispensable for understanding the intrinsic interface properties of GO.

Laboratory Test Predictors for Major Bleeding in Elderly (≥80 Years) Patients With Nonvalvular Atrial Fibrillation Treated With Edoxaban 15 mg: Sub-Analysis of the ELDERCARE-AF Trial.

Background We investigated the predictors related to major bleeding events during treatment with edoxaban 15 mg in patients aged ≥80 years with nonvalvular atrial fibrillation and high bleeding risk, for whom standard oral anticoagulants are inappropriate, focusing on standard laboratory tests related to bleeding. Methods and Results This was a prespecified subanalysis of the on-treatment analysis set of the ELDERCARE-AF (Edoxaban Low-Dose for Elder Care Atrial Fibrillation Patients) trial. Major bleeding was the primary safety end point. The event rates were calculated according to prespecified characteristics at baseline. A total of 984 Japanese patients were randomly assigned to edoxaban 15 mg or placebo (n=492, each). During the study period, 20 and 11 major bleeding events occurred in the edoxaban and placebo groups, respectively. The adjusted analysis revealed that hemoglobin <12.3 g/dL (adjusted hazard ratio [aHR], 3.57 [95% CI, 1.10-11.55]) and prothrombin time ≥12.7 seconds; (aHR, 2.89 [95% CI, 1.05-8.02]) independently predicted major bleeding, while creatinine clearance <30 mL/min showed a tendency towards an increase in major bleeding (aHR, 2.68; 95% CI, 0.96-7.46). In patients treated with edoxaban lacking these 3 risk factors, no major bleeding occurred; major bleeding event rates increased with each risk factor. Patients with 3 risk factors were significantly more likely to have a major bleeding event at 11.05%/year (HR, 7.15 [95% CI, 1.92-26.71]). Conclusions In elderly patients with nonvalvular atrial fibrillation with high bleeding risk, baseline hemoglobin <12.3 g/dL, prothrombin time ≥12.7 seconds, and creatinine clearance <30 mL/min may predict major bleeding during treatment with edoxaban 15 mg. Registration URL: ELDERCARE-AF https://www.clinicaltrials.gov; Unique number: NCT02801669.

Outcomes and Safety of Very-Low-Dose Edoxaban in Frail Patients With Atrial Fibrillation in the ELDERCARE-AF Randomized Clinical Trial.

Importance: The prevalence of atrial fibrillation (AF) increases with age and is more common in frail patients. However, data are lacking on outcomes of oral anticoagulants (OACs) in very elderly patients with AF with frailty, who are ineligible for standard anticoagulant treatment. Objective: To compare very-low-dose edoxaban (15 mg daily) vs placebo across frailty status, including each of 5 frailty assessment parameters, among patients with AF involved in the ELDERCARE-AF (Edoxaban Low-Dose for Elder Care Atrial Fibrillation Patients) trial. Design, Setting, and Participants: This is a cohort study using data from ELDERCARE-AF, a multicenter, randomized, double-blind, placebo-controlled phase 3 study of Japanese patients with AF aged 80 years or older who were ineligible for OACs at doses approved for stroke prevention because of their high bleeding risks. Eligible patients were randomly assigned (1:1) to receive edoxaban or placebo. The study duration was from August 5, 2016, to November 5, 2019, with the last patient followed up on December 27, 2019. Data analysis was performed from February 2021 to February 2022. Exposure: Edoxaban (15 mg) once daily or placebo. Main Outcomes and Measures: The primary efficacy end point was the composite of stroke or systemic embolism, and the primary safety end point was major bleeding. Results: A total of 984 patients were randomly assigned to treatment (492 each to the edoxaban and placebo groups); 944 patients (402 frail patients [42.6%]; 542 nonfrail patients [57.4%]; mean [SD] age, 86.6 [4.3] years; 541 women [57.3%]) were included in this analysis. In the placebo group, the estimated event rates (SE) for stroke or systemic embolism were 7.1% (1.6%) per patient-year in the frail group and 6.1% (1.3%) per patient-year in the nonfrail group. Edoxaban was associated with lower event rates for stroke or systemic embolism with no interaction with frailty status or frailty assessment parameters. Major bleeding and major or clinically relevant nonmajor bleeding events were both numerically higher in the edoxaban group than in the placebo group, and no heterogeneity was observed with frailty status. Although both all-cause death and net clinical composite outcome occurred more frequently in the frail group than in the nonfrail group, there was no association with frailty status between the edoxaban and placebo groups. Conclusions and Relevance: Regardless of frailty status, among Japanese patients with AF aged 80 years or older who were ineligible for standard OACs, once-daily 15-mg edoxaban was associated with reduced incidence of stroke or systemic embolism and may be a suitable treatment option for these patients.

Interlocking of Single-Walled Carbon Nanotubes with Metal-Tethered Tetragonal Nanobrackets to Enrich a Few Hundredths of a Nanometer Range in Their Diameters.

We have separated carbon nanotubes through host-guest complexation using host molecules named "nanotweezers" and "nanocalipers". In this work, a host molecule named tetragonal "M-nanobrackets", consisting of a pair of dipyrrin nanocalipers corresponding to two brackets "[" and "]" tethered by two metals (M), is designed, synthesized, and employed to separate single-walled carbon nanotubes (SWNTs). A facile three-step process including one-pot Suzuki coupling is developed to synthesize M-nanobrackets in a 37% total yield (M = Cu). Upon extraction of SWNTs with a square nanobracket and Cu(II), in situ formed tetragonal M-nanobrackets are found to interlock SWNTs to disperse them in 2-propanol. The interlocking is confirmed by absorption and Raman spectroscopy as well as transmission electron and atomic force microscopy. Especially, Raman spectroscopy is utilized to prove the interlocking of SWNTs; Cu-nanobrackets are found to show inherent resonance Raman signals and affect the SWNT signals, or a radial breathing vibration, due to the rigid rectangular structure of Cu-nanobrackets. The interlocking is facilely and thoroughly released through demetalation to recover the pristine SWNTs as well as the square nanobracket. Such chemically controlled locking and unlocking for SWNTs are one of the characteristics of our separation process. This enables a precise evaluation by Raman, photoluminescence, and absorption spectroscopy of the diameter selectivity to SWNTs, revealing the diameter enrichment of only three kinds of SWNTs, (7,6), (9,4), and (8,5), in the 0.02 nm diameter range from 0.90 to 0.92 nm among ∼20 kinds of SWNTs from 0.76 to 1.17 nm in their diameter range.

ARDS Clinical Practice Guideline 2021.

BACKGROUND: The joint committee of the Japanese Society of Intensive Care Medicine/Japanese Respiratory Society/Japanese Society of Respiratory Care Medicine on ARDS Clinical Practice Guideline has created and released the ARDS Clinical Practice Guideline 2021. METHODS: The 2016 edition of the Clinical Practice Guideline covered clinical questions (CQs) that targeted only adults, but the present guideline includes 15 CQs for children in addition to 46 CQs for adults. As with the previous edition, we used a systematic review method with the Grading of Recommendations Assessment Development and Evaluation (GRADE) system as well as a degree of recommendation determination method. We also conducted systematic reviews that used meta-analyses of diagnostic accuracy and network meta-analyses as a new method. RESULTS: Recommendations for adult patients with ARDS are described: we suggest against using serum C-reactive protein and procalcitonin levels to identify bacterial pneumonia as the underlying disease (GRADE 2D); we recommend limiting tidal volume to 4-8 mL/kg for mechanical ventilation (GRADE 1D); we recommend against managements targeting an excessively low SpO2 (PaO2) (GRADE 2D); we suggest against using transpulmonary pressure as a routine basis in positive end-expiratory pressure settings (GRADE 2B); we suggest implementing extracorporeal membrane oxygenation for those with severe ARDS (GRADE 2B); we suggest against using high-dose steroids (GRADE 2C); and we recommend using low-dose steroids (GRADE 1B). The recommendations for pediatric patients with ARDS are as follows: we suggest against using non-invasive respiratory support (non-invasive positive pressure ventilation/high-flow nasal cannula oxygen therapy) (GRADE 2D), we suggest placing pediatric patients with moderate ARDS in the prone position (GRADE 2D), we suggest against routinely implementing NO inhalation therapy (GRADE 2C), and we suggest against implementing daily sedation interruption for pediatric patients with respiratory failure (GRADE 2D). CONCLUSIONS: This article is a translated summary of the full version of the ARDS Clinical Practice Guideline 2021 published in Japanese (URL: https://www.jsicm.org/publication/guideline.html ). The original text, which was written for Japanese healthcare professionals, may include different perspectives from healthcare professionals of other countries.

ARDS clinical practice guideline 2021.

BACKGROUND: The joint committee of the Japanese Society of Intensive Care Medicine/Japanese Respiratory Society/Japanese Society of Respiratory Care Medicine on ARDS Clinical Practice Guideline has created and released the ARDS Clinical Practice Guideline 2021. METHODS: The 2016 edition of the Clinical Practice Guideline covered clinical questions (CQs) that targeted only adults, but the present guideline includes 15 CQs for children in addition to 46 CQs for adults. As with the previous edition, we used a systematic review method with the Grading of Recommendations Assessment Development and Evaluation (GRADE) system as well as a degree of recommendation determination method. We also conducted systematic reviews that used meta-analyses of diagnostic accuracy and network meta-analyses as a new method. RESULTS: Recommendations for adult patients with ARDS are described: we suggest against using serum C-reactive protein and procalcitonin levels to identify bacterial pneumonia as the underlying disease (GRADE 2D); we recommend limiting tidal volume to 4-8 mL/kg for mechanical ventilation (GRADE 1D); we recommend against managements targeting an excessively low SpO2 (PaO2) (GRADE 2D); we suggest against using transpulmonary pressure as a routine basis in positive end-expiratory pressure settings (GRADE 2B); we suggest implementing extracorporeal membrane oxygenation for those with severe ARDS (GRADE 2B); we suggest against using high-dose steroids (GRADE 2C); and we recommend using low-dose steroids (GRADE 1B). The recommendations for pediatric patients with ARDS are as follows: we suggest against using non-invasive respiratory support (non-invasive positive pressure ventilation/high-flow nasal cannula oxygen therapy) (GRADE 2D); we suggest placing pediatric patients with moderate ARDS in the prone position (GRADE 2D); we suggest against routinely implementing NO inhalation therapy (GRADE 2C); and we suggest against implementing daily sedation interruption for pediatric patients with respiratory failure (GRADE 2D). CONCLUSIONS: This article is a translated summary of the full version of the ARDS Clinical Practice Guideline 2021 published in Japanese (URL: https://www.jrs.or.jp/publication/jrs_guidelines/). The original text, which was written for Japanese healthcare professionals, may include different perspectives from healthcare professionals of other countries.

Empirical transmit field bias correction of T1w/T2w myelin maps.

T1-weighted divided by T2-weighted (T1w/T2w) myelin maps were initially developed for neuroanatomical analyses such as identifying cortical areas, but they are increasingly used in statistical comparisons across individuals and groups with other variables of interest. Existing T1w/T2w myelin maps contain radiofrequency transmit field (B1+) biases, which may be correlated with these variables of interest, leading to potentially spurious results. Here we propose two empirical methods for correcting these transmit field biases using either explicit measures of the transmit field or alternatively a 'pseudo-transmit' approach that is highly correlated with the transmit field at 3T. We find that the resulting corrected T1w/T2w myelin maps are both better neuroanatomical measures (e.g., for use in cross-species comparisons), and more appropriate for statistical comparisons of relative T1w/T2w differences across individuals and groups (e.g., sex, age, or body-mass-index) within a consistently acquired study at 3T. We recommend that investigators who use the T1w/T2w approach for mapping cortical myelin use these B1+ transmit field corrected myelin maps going forward.

Prognosis of elderly non-valvular atrial fibrillation patients stratified by B-type natriuretic peptide: ELDERCARE-AF subanalysis.

BACKGROUND: B-type natriuretic peptide (BNP) is a risk factor for stroke and cardiac death in patients with atrial fibrillation. We hypothesized the prognostic outcomes of very elderly non-valvular atrial fibrillation patients ineligible for standard anticoagulation treatment would vary according to BNP stratification. METHODS: In this subanalysis of the ELDERCARE-AF trial, patients were stratified by BNP levels at enrollment, and clinical outcomes compared among BNP subgroups. Hazard ratios were adjusted for age, atrial fibrillation type, body mass index, creatine clearance, congestive heart failure, and D-dimer. BNP levels were measured using chemiluminescence enzyme immunoassays. RESULTS: In total, 984 patients (average age: 86.6 years) not considered eligible for oral anticoagulant therapy at approved doses for stroke prevention were included. The BNP levels at enrollment were <200 (low), 200 to <400 (moderate), and ≥400 (high) pg/mL in 428, 300, and 256 patients, respectively. The number (%) of patients with stroke or systemic embolism (SSE) was 7 (1.2%), 24 (5.9%), and 28 (8.6%) in the low, moderate, and high BNP subgroups, respectively (adjusted hazard ratio 3.82, P = .0025 for low vs moderate BNP and 4.76, P = .0007 for low vs high BNP). There was no significant difference in major bleeding incidence between the BNP subgroups. Edoxaban 15 mg was associated with a consistent reduction in SSE vs placebo in all BNP subgroups. CONCLUSIONS: Stratification by BNP level was associated with the incidence of SSE for very elderly non-valvular atrial fibrillation patients ineligible for standard anticoagulation treatment, and the effect of edoxaban 15 mg was consistent across BNP levels.

Ultrapermeable 2D-channeled graphene-wrapped zeolite molecular sieving membranes for hydrogen separation.

The efficient separation of hydrogen from methane and light hydrocarbons for clean energy applications remains a technical challenge in membrane science. To address this issue, we prepared a graphene-wrapped MFI (G-MFI) molecular-sieving membrane for the ultrafast separation of hydrogen from methane at a permeability reaching 5.8 × 106 barrers at a single gas selectivity of 245 and a mixed gas selectivity of 50. Our results set an upper bound for hydrogen separation. Efficient molecular sieving comes from the subnanoscale interfacial space between graphene and zeolite crystal faces according to molecular dynamic simulations. The hierarchical pore structure of the G-MFI membrane enabled rapid permeability, indicating a promising route for the ultrafast separation of hydrogen/methane and carbon dioxide/methane in view of energy-efficient industrial gas separation.