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We propose an experimental method for evaluating the adiabatic condition during quantum annealing (QA), which will be essential for solving practical problems. The adiabatic condition consists of the transition matrix element and the energy gap, and our method simultaneously provides information about these components without diagonalizing the Hamiltonian. The key idea is to measure the power spectrum of a time domain signal by adding an oscillating field during QA, and we can estimate the values of the transition matrix element and energy gap from the measurement output. Our results provides a powerful experimental basis for analyzing the performance of QA.

Japan has conducted a nationwide annual health check-up program since 2008, focusing on metabolic syndrome and subsequent health guidance in individuals at high risk for cardiovascular disease. However, the adherence rate to health guidance invitations was assumed to be low in previous reports. Therefore, this study aimed to characterize adherence patterns in the program and identify major predictors of adherence to health guidance invitations. We studied 186,316 adults (aged 40-74 years) who were included in a nationwide employer-sponsored insurer's database in Japan at the beginning of the fiscal year 2017. We first described adherence to health check-ups, the proportion of individuals with high cardiovascular risk, and adherence to health guidance invitations. Predictors of adherence to the invitation were then identified among eligible high-risk individuals. In 2017, 71.7% of the study population (n = 133,573) underwent health check-ups, among whom 23.2% (n = 30,979) were invited for health guidance because of their high cardiovascular risk. Among those individuals, 35.2% (n = 10,614) received health guidance. Predictors of improved adherence to health guidance invitation were older age, more concerning blood pressure or laboratory data results, and self-reported motivation for a lifestyle change. Though 70% of eligible adults attended Japan's annual cardiovascular risk check-ups, only 35% of individuals with high cardiovascular risk adhered to health guidance invitations. Future policy reforms to improve adherence to this program should target younger individuals and those with mild stages of hypertension, diabetes, or dyslipidemia.

The formulation of accurate clinical case definitions is an integral part of an effective process of public health surveillance. Although such definitions should, ideally, be based on a standardized and fixed collection of defining criteria, they often require revision to reflect new knowledge of the condition involved and improvements in diagnostic testing. Optimal case definitions also need to have a balance of sensitivity and specificity that reflects their intended use. After the 2009-2010 H1N1 influenza pandemic, the World Health Organization (WHO) initiated a technical consultation on global influenza surveillance. This prompted improvements in the sensitivity and specificity of the case definition for influenza - i.e. a respiratory disease that lacks uniquely defining symptomology. The revision process not only modified the definition of influenza-like illness, to include a simplified list of the criteria shown to be most predictive of influenza infection, but also clarified the language used for the definition, to enhance interpretability. To capture severe cases of influenza that required hospitalization, a new case definition was also developed for severe acute respiratory infection in all age groups. The new definitions have been found to capture more cases without compromising specificity. Despite the challenge still posed in the clinical separation of influenza from other respiratory infections, the global use of the new WHO case definitions should help determine global trends in the characteristics and transmission of influenza viruses and the associated disease burden.

Insufficient blood pressure control among patients with hypertension without elevated risk is a global concern, suggesting the need for treatment optimization. However, the potential harm of excessive blood pressure lowering among these patients is understudied. This study addressed this evidence gap by using nationally representative public health insurer database covering 30 million working-age population. Patients who were continuously using antihypertensive drugs with 10-year cardiovascular risk <10% were identified. They were categorized by on-treatment systolic and diastolic blood pressures. The primary outcome was a composite of myocardial infarction, stroke, heart failure hospitalization, and peripheral artery disease. Of 920,533 participants (mean age, 57.3 years; female, 48.3%; mean follow-up, 2.75 years), the adjusted hazard ratios for systolic blood pressure of <110, 110–119, 120–129 (reference), 130–139, 140–149, 150–159, and ≥160 mmHg were 1.05 (95% confidence interval: 0.99–1.12), 0.97 (0.93–1.02), 1 (reference), 1.05 (1.01–1.09), 1.15 (1.11–1.20), 1.30 (1.23–1.37), and 1.76 (1.66–1.86), respectively; and for diastolic blood pressure of <60, 60–69, 70–79 (reference), 80–89, 90–99, and ≥100 mmHg were 1.25 (1.14–1.38), 0.99 (0.95–1.04), 1 (reference), 1.00 (0.96–1.03), 1.13 (1.09–1.18), and 1.66 (1.58–1.76), respectively. Among low-risk patients with hypertension, diastolic blood pressure <60 mmHg was associated with increased cardiovascular events, while systolic blood pressure <110 mmHg was not. Compared to previous investigations in high-risk patients, the potential harm of excessive blood pressure lowering was less pronounced in low-risk patients with hypertension.

ObjectivesWe aimed to investigate the association between repetitive proteinuria and cardiovascular events among the middle-aged and older general Japanese population.DesignRetrospective cohort study.SettingWe used repeated health screening results and medical claim data from one of the largest health insurers in Japan.ParticipantsAmong the middle-aged and older participants (40–74 years, n=179 840), 90 752 were excluded for undergoing health screening fewer than two times and 344 were excluded for having a history of cardiovascular diseases; 88 744 who underwent kidney function screenings at least two times (from April 2011 to March 2015) were included in the analysis. Based on dipstick proteinuria test results, the participants were divided into ‘Repetitively-positive’ (positive two times or more (positive proteinuria was defined as≥1+)), ‘Once-positive’ and ‘All-negative’ groups.Primary and secondary outcome measuresThe primary outcome of major cardiovascular events from baseline screening to June 2021 was hospitalisation or death due to acute myocardial infarction (AMI), cerebrovascular diseases, heart failure (HF) or peripheral vascular diseases (PVDs). The association between proteinuria and major cardiovascular events was assessed using a Cox proportional hazards model.ResultsOf the 88 744 participants, 8775 (9.9%) and 5498 (6.2%) had Once-positive and Repetitively-positive proteinuria, respectively. During the follow-up period of 402 799 person-years (median 5.25 years), 660 cardiovascular events were observed, with an incidence of 1.64 per 1000 person-years (95% CI 1.52 to 1.77). Despite adjusting for major cardiovascular risk factors, we observed a high incidence of cardiovascular events in the Repetitively-positive (HR 2.08, 95% CI 1.67 to 2.59) and Once-positive groups (HR 1.36, 95% CI 1.07 to 1.72). We found similar associations for AMI, cerebrovascular disease, HF and PVD.ConclusionsProteinuria is often repeatedly detected during annual renal screening in the general population. Repetitive proteinuria is a risk factor for major cardiovascular events.

Hydrogen (H) is considered to be one of the candidates for light elements in the Earth’s core, but the amount and timing of delivery have been unknown. We investigated the effects of sulfur (S), another candidate element in the core, on deuteration of iron (Fe) in iron–silicate–water system up to 6–12 GPa, ~ 1200 K using in situ neutron diffraction measurements. The sample initially contained saturated water (D 2 O) as Mg(OD) 2 in the ideal composition (Fe–MgSiO 3 –D 2 O) of the primitive Earth. In the existence of water and sulfur, phase transitions of Fe, dehydration of Mg(OD) 2 , and formation of iron sulfide (FeS) and silicates occurred with increasing temperature. The deuterium (D) solubility ( x ) in iron deuterides (FeD x ) increased with temperature and pressure, resulting in a maximum of x  = 0.33(4) for the hydrous sample without S at 11.2 GPa and 1067 K. FeS was hardly deuterated until Fe deuteration had completed. The lower D concentrations in the S-containing system do not exceed the miscibility gap ( x  <  ~ 0.4). Both H and S can be incorporated into solid Fe and other light elements could have dissolved into molten iron hydride and/or FeS during the later process of Earth’s evolution.

A previous study demonstrated that the per capita volume of percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI) was relatively uniform across the 47 prefectures in Japan, while elective PCIs for stable coronary artery disease showed wide regional variation. However, contemporary data remain limited. The Japanese PCI (J-PCI) is a nationwide prospective registry covering most of the procedures performed within the country. PCI procedures in 2019 and 2023 were included and divided according to the indications: AMI versus non-AMI. The patterns of PCI procedures performed for AMI and non-AMI across all prefectures in Japan were evaluated. The associations of the non-AMI/AMI ratio with population, area, and the number of PCI-capable centers per prefecture were also assessed. A total of 494,746 PCI procedures were analyzed. The ratios between the highest and lowest prefectures were 4.0-fold in non-AMI and 1.9-fold in AMI in 2019 and 4.2-fold in non-AMI and 2.0-fold in AMI in 2023. The non-AMI/AMI ratio was positively correlated with the ratios of the number of PCI-capable centers to population and area per prefecture. Geographic disparity was observed in the relative volume of PCI performed for AMI compared to non-AMI across Japan, potentially reflecting variations in the density of PCI-capable centers relative to the area and population of each prefecture.

Aims Natriuretic peptide‐based pre‐heart failure screening has been proposed in recent guidelines. However, an effective strategy to identify screening targets from the general population, more than half of which are at risk for heart failure or pre‐heart failure, has not been well established. This study evaluated the performance of machine learning prediction models for predicting elevated N terminal pro brain natriuretic peptide (NT‐proBNP) levels in the US general population. Methods and results Individuals aged 20–79 years without cardiovascular disease from the nationally representative National Health and Nutrition Examination Survey 1999–2004 were included. Six prediction models (two conventional regression models and four machine learning models) were trained with the 1999–2002 cohort to predict elevated NT‐proBNP levels (>125 pg/mL) using demographic, lifestyle, and commonly measured biochemical data. The model performance was tested using the 2003–2004 cohort. Of the 10 237 individuals, 1510 (14.8%) had NT‐proBNP levels >125 pg/mL. The highest area under the receiver operating characteristic curve (AUC) was observed in SuperLearner (AUC [95% CI] = 0.862 [0.847–0.878], P < 0.001 compared with the logistic regression model). The logistic regression model with splines showed a comparable performance (AUC [95% CI] = 0.857 [0.841–0.874], P = 0.08). Age, albumin level, haemoglobin level, sex, estimated glomerular filtration rate, and systolic blood pressure were the most important predictors. We found a similar prediction performance even after excluding socio‐economic information (marital status, family income, and education status) from the prediction models. When we used different thresholds for elevated NT‐proBNP, the AUC (95% CI) in the SuperLearner models 0.846 (0.830–0.861) for NT‐proBNP > 100 pg/mL and 0.866 (0.849–0.884) for NT‐proBNP > 150 pg/mL. Conclusions Using nationally representative data from the United States, both logistic regression and machine learning models well predicted elevated NT‐proBNP. The predictive performance remained consistent even when the models incorporated only commonly available variables in daily clinical practice. Prediction models using regularly measured information would serve as a potentially useful tools for clinicians to effectively identify targets of natriuretic‐peptide screening.

We have developed an efficient system for triphase reactions using a microchannel reactor. Using this system, we conducted hydrogenation reactions that proceeded smoothly to afford the desired products quantitatively within 2 minutes for a variety of substrates. The system could also be applied to deprotection reactions. We could achieve an effective interaction between hydrogen, substrates, and a palladium catalyst using extremely large interfacial areas and the short path required for molecular diffusion in the very narrow channel space. This concept could be extended to other multiphase reactions that use gas-phase reagents such as oxygen and carbon dioxide.

Background Patients with low-to-normal body mass index (BMI; < 25.0 kg/m 2 ) were underrepresented in major randomized controlled trials on sodium-glucose cotransporter 2 (SGLT2) inhibitors for type 2 diabetes. The present study aims to investigate the effectiveness of SGLT2 inhibitors for cardiovascular outcomes among patients with type 2 diabetes and low-to-normal BMI, using finer stratification than previous trials. Methods This cohort study with a target trial emulation framework was conducted using insurance claims and health screening records of more than 30 million working-age citizens in Japan acquired from April 1, 2015 to March 31, 2022. 139,783 new users of SGLT2 inhibitors matched to 139,783 users of dipeptidyl protease (DPP) 4 inhibitors with stratification by BMI category (< 20.0, 20.0–22.4, 22.5–24.9, 25.0–29.9, 30.0–34.9, and 35.0 ≤ kg/m 2 ). The primary outcome was a composite of all-cause death, myocardial infarction, stroke, or heart failure. Secondary outcomes were the components of the primary outcome. Cox proportional hazard models were used to compare SGLT2 inhibitors with DPP4 inhibitors in the whole population and subgroups defined by the BMI category. Results Among participants, 17.3% (n = 48,377) were female and 31.0% (n = 86,536) had low-to-normal BMI (< 20.0 kg/m 2 , 1.9% [n = 5,350]; 20.0–22.4 kg/m 2 , 8.5% [n = 23,818]; and 22.5–24.9 kg/m 2 , 20.5% [n = 57,368]). Over a median follow-up of 24 months, the primary outcome occurred in 2.9% (n = 8,165) of participants. SGLT2 inhibitors were associated with a decreased incidence of the primary outcome in the whole population (HR [95%CI] = 0.92 [0.89 to 0.96]), but not in patients with low-to-normal BMI (< 20.0 kg/m 2 , HR [95%CI] = 1.08 [0.80 to 1.46]; 20.0–22.4 kg/m 2 , HR [95%CI] = 1.04 [0.90 to 1.20]; and 22.5–24.9 kg/m 2 , HR [95%CI] = 0.92 [0.84 to 1.01]). Conclusions The protective effect of SGLT2 inhibitors on cardiovascular events among patients with type 2 diabetes appeared to decrease with lower BMI and was not significant among patients with low-to-normal BMI (< 25.0 kg/m2). These findings suggest the importance of considering BMI when initiating SGLT2 inhibitors. Graphical abstract