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The capability of state-of-the-art techniques integrating experimental and computational fluid dynamics has been expanding recently. In our previous study, we have developed a hybrid unsteady-flow simulation technique combining particle tracking velocimetry (PTV) and direct numerical simulation (DNS) and demonstrated its capability at low Reynolds numbers. Similar approaches have also been proposed by a few groups; however, applying algorithms of this type generally becomes more challenging with increasing Reynolds number because the time interval of the frame rate for particle image velocimetry (PIV) becomes much greater than the required computational time step, and the PIV/PTV resolution tends to be lower than that necessary for computational fluid dynamics. To extend the applicability to noisy time-resolved PIV/PTV data, the proposed algorithm optimizes the data input temporally and spatially by introducing a reduced-order Kalman filter. This study establishes a framework of the Kalman-filtered hybrid simulation and proves the concept by tackling a planar-jet flow at $\\mathit{Re}\\approx 2000$ as an example. We evaluate the filtering functions as well as convergence of the proposed algorithm by comparing with the existing PTV–DNS hybrid simulation, and show some techniques available to hybrid velocity fields by analysing vortical motion in the shear layers of the jet.

Current genome-wide association studies do not yet capture sufficient diversity in populations and scope of phenotypes. To expand an atlas of genetic associations in non-European populations, we conducted 220 deep-phenotype genome-wide association studies (diseases, biomarkers and medication usage) in BioBank Japan ( n  = 179,000), by incorporating past medical history and text-mining of electronic medical records. Meta-analyses with the UK Biobank and FinnGen ( n total  = 628,000) identified ~5,000 new loci, which improved the resolution of the genomic map of human traits. This atlas elucidated the landscape of pleiotropy as represented by the major histocompatibility complex locus, where we conducted HLA fine-mapping. Finally, we performed statistical decomposition of matrices of phenome-wide summary statistics, and identified latent genetic components, which pinpointed responsible variants and biological mechanisms underlying current disease classifications across populations. The decomposed components enabled genetically informed subtyping of similar diseases (for example, allergic diseases). Our study suggests a potential avenue for hypothesis-free re-investigation of human diseases through genetics. Genome-wide analyses in BioBank Japan, UK Biobank and FinnGen identify ~5,000 new loci associated with 220 human traits. Statistical decomposition of matrices of phenome-wide summary statistics further highlights variants underpinning diseases across populations.

We propose a diagnostic technique to detect instability waves in a subsonic round jet using a phased microphone array. The detection algorithm is analogous to the beam-forming technique, which is typically used with a far-field microphone array to localize noise sources. By replacing the reference solutions used in the conventional beam-forming with eigenfunctions from linear stability analysis, the amplitudes of instability waves in the axisymmetric and first two azimuthal modes are inferred. Experimental measurements with particle image velocimetry and a database from direct numerical simulation are incorporated to design a conical array that is placed just outside the mixing layer near the nozzle exit. The proposed diagnostic technique is tested in experiments by checking for consistency of the radial decay, streamwise evolution and phase correlation of hydrodynamic pressure. The results demonstrate that in a statistical sense, the pressure field is consistent with instability waves evolving in the turbulent mean flow from the nozzle exit to the end of the potential core, particularly near the most amplified frequency of each azimuthal mode. We apply this technique to study the effects of jet Mach number and temperature ratio on the azimuthal mode balance and evolution of instability waves. We also compare the results from the beam-forming algorithm with the proper orthogonal decomposition and discuss some implications for jet noise.

ObjectiveTo examine the relationship between physical frailty and risk of disability, and to identify the component(s) of frailty with the most impact on disability in community-dwelling older adults.DesignProspective cohort study.SettingA Japanese community.Participants4341 older adults aged ≥65 living in the community participated in a baseline assessment from 2011 to 2012 and were followed for 2 years.Main outcome measuresCare-needs certification in the national long-term care insurance (LTCI) system of Japan, type of physical frailty (robust, prefrail, frail) and subitems (slowness, weakness, exhaustion, low activity, weight loss), adjusted for several potential confounders such as demographic characteristics, analysed with Kaplan-Meier survival curves for incidence of disability by frailty phenotype.ResultsDuring the 2-year follow-up period, 168 participants (3.9%) began using the LTCI system for incidence of disability. Participants classified as frail (HR 4.65, 95% CI 2.63 to 8.22) or prefrail (2.52, 1.56 to 4.07) at the baseline assessment had an increased risk of disability incidence compared with robust participants. Analyses for subitems of frailty showed that slowness (2.32, 1.62 to 3.33), weakness (1.90, 1.35 to 2.68) and weight loss (1.61, 1.13 to 2.31) were related to increased risk of disability incidence. In stratified analyses, participants who were classified as frail and who had lower cognitive function had the highest percentage (30.3%) of disability incidence during the 2 years after baseline assessment.ConclusionsPhysical frailty, even being prefrail, had a strong impact on the risk of future disability. Some components of frailty, such as slowness, weakness and weight loss, are strongly associated with incident disability in community-dwelling older adults.

The unsteady flow estimation problem of wall-bounded turbulence, numerically benchmarked by Chevalier et al. ( J. Fluid Mech. , vol. 552, 2006, pp. 167–187), is re-tackled with simple approaches. A turbulent channel flow at$Re_{\\unicode[STIX]{x1D70F}}=100$with periodic boundary conditions is reconstructed with linear stochastic estimation only based on the wall measurement, i.e. the wall shear stress in the streamwise and spanwise directions as well as the wall pressure over the entire wavenumber space. The results reveal that instantaneous information on the wall governs the success of the estimation in the vicinity of the wall ($y^{+}\\lesssim 20$). The degrees of agreement are equivalent to those reported by Chevalier et al. using the extended Kalman filter as well as the ensemble Kalman filter performed in this study. This suggests that the instantaneous information on the wall dictates the reconstruction rather than the prediction step in these state observers solving the dynamical system. Subsequently, we feed the velocity components given by the linear stochastic estimation via the body-force term into the Navier–Stokes system: such an observer slightly improves the estimation in the log layer, indicating a small benefit of involving a dynamical system but over-suppression of turbulent motions beyond the viscous sublayer due to their low correlation with the wall measurement. Errors in the estimation grow in the buffer layer and prevent further reconstruction toward the centreline even if we relax the feedback forcing and let the flow evolve nonlinearly through the observer. We also discuss the flow components truly reconstructible from the wall measurement, which has limited degrees of freedom and poor correlation across wavenumbers.

Polygenic risk scores suffer reduced accuracy in non-European populations, exacerbating health disparities. We propose PolyPred, a method that improves cross-population polygenic risk scores by combining two predictors: a new predictor that leverages functionally informed fine-mapping to estimate causal effects (instead of tagging effects), addressing linkage disequilibrium differences, and BOLT-LMM, a published predictor. When a large training sample is available in the non-European target population, we propose PolyPred + , which further incorporates the non-European training data. We applied PolyPred to 49 diseases/traits in four UK Biobank populations using UK Biobank British training data, and observed relative improvements versus BOLT-LMM ranging from +7% in south Asians to +32% in Africans, consistent with simulations. We applied PolyPred + to 23 diseases/traits in UK Biobank east Asians using both UK Biobank British and Biobank Japan training data, and observed improvements of +24% versus BOLT-LMM and +12% versus PolyPred. Summary statistics-based analogs of PolyPred and PolyPred + attained similar improvements. PolyPred and PolyPred + methods that leverage fine-mapping and non-European training data significantly improve cross-population polygenic prediction accuracy when applied to diseases and complex traits in UK Biobank populations.

Musculoskeletal diseases, especially osteoarthritis (OA) and osteoporosis (OP), impair activities of daily life (ADL) and quality of life (QOL) in the elderly. Although preventive strategies for these diseases are urgently required in an aging society, epidemiological data on these diseases are scant. To clarify the prevalence of knee osteoarthritis (KOA), lumbar spondylosis (LS), and osteoporosis (OP) in Japan, and estimate the number of people with these diseases, we started a large-scale population-based cohort study entitled research on osteoarthritis/osteoporosis against disability (ROAD) in 2005. This study involved the collection of clinical information from three cohorts composed of participants located in urban, mountainous, and coastal areas. KOA and LS were radiographically defined as a grade of >=2 by the Kellgren-Lawrence scale; OP was defined by the criteria of the Japanese Society for Bone and Mineral Research. The 3,040 participants in total were divided into six groups based on their age: <=39, 40-49, 50-59, 60-69, 70-79, and >=80 years. The prevalence of KOA in the age groups <=39, 40-49, 50-59, 60-69, 70-79, and >=80 years 0, 9.1, 24.3, 35.2, 48.2, and 51.6%, respectively, in men, and the prevalence in women of the same age groups was 3.2, 11.4, 30.3, 57.1, 71.9, and 80.7%, respectively. With respect to the age groups, the prevalence of LS was 14.3, 45.5, 72.9, 74.6, 85.3, and 90.1% in men, and 9.7, 28.6, 41.7, 55.4, 75.1, and 78.2% in women, respectively. Data of the prevalence of OP at the lumbar spine and femoral neck were also obtained. The estimated number of patients with KOA, LS, and L2-L4 and femoral neck OP in Japan was approximately 25, 38, 6.4, and 11 million, respectively. In summary, we estimated the prevalence of OA and OP, and the number of people affected with these diseases in Japan. The ROAD study will elucidate epidemiological evidence concerning determinants of bone and joint disease.

The prevalence of disability is increasing due to an expanding aging population and an increasing incidence of chronic health problems. Cognitive impairment may predict the development of disability in older adults. Therefore, we examined the association of mild cognitive impairment (MCI) and/or general cognitive impairment (GCI, defined as a Mini Mental State Examination [MMSE] score of 20-23) with the development of disability in a cohort of Japanese community-dwelling older adults. A total of 4290 participants (aged ≥65 years) enrolled in the Obu Study of Health Promotion for the Elderly were classified according to the presence and degree of cognitive impairment as follows: cognitively healthy, GCI, MCI single domain (MCIs), MCIs with GCI, MCI multiple domain (MCIm), and MCIm with GCI. MMSE scores, risk factors for dementia, and incidences of new disability were recorded. After an average of 29.5 months, 205 participants (4.8%) experienced a new onset of disability. All subtypes of cognitive impairment showed significant relationships with disability except for GCI alone. The following hazard ratios (HRs) were determined: MCIs (HR, 2.04; 95% CI, 1.39-3.00), MCIs with GCI (HR, 2.10; 95% CI, 1.21-3.62), MCIm (HR, 2.32; 95% CI, 1.39-3.85), and MCIm with GCI (HR, 4.23; 95% CI, 2.73-6.57). These results indicate that cognitive impairment may be related to an increased risk for the development of disability. Healthcare providers should implement global cognitive assessments to identify MCI and GCI and consider preventive interventions for disability, especially in older persons.

To examine the effect of multicomponent exercise program on memory function in older adults with mild cognitive impairment (MCI), and identify biomarkers associated with improvement of cognitive functions. Subjects were 100 older adults (mean age, 75 years) with MCI. The subjects were classified to an amnestic MCI group (n = 50) with neuroimaging measures, and other MCI group (n = 50) before the randomization. Subjects in each group were randomized to either a multicomponent exercise or an education control group using a ratio of 1∶1. The exercise group exercised for 90 min/d, 2 d/wk, 40 times for 6 months. The exercise program was conducted under multitask conditions to stimulate attention and memory. The control group attended two education classes. A repeated-measures ANOVA revealed that no group × time interactions on the cognitive tests and brain atrophy in MCI patients. A sub-analysis of amnestic MCI patients for group × time interactions revealed that the exercise group exhibited significantly better Mini-Mental State Examination (p = .04) and logical memory scores (p = .04), and reducing whole brain cortical atrophy (p<.05) compared to the control group. Low total cholesterol levels before the intervention were associated with an improvement of logical memory scores (p<.05), and a higher level of brain-derived neurotrophic factor was significantly related to improved ADAS-cog scores (p<.05). The results suggested that an exercise intervention is beneficial for improving logical memory and maintaining general cognitive function and reducing whole brain cortical atrophy in older adults with amnestic MCI. Low total cholesterol and higher brain-derived neurotrophic factor may predict improvement of cognitive functions in older adults with MCI. Further studies are required to determine the positive effects of exercise on cognitive function in older adults with MCI. UMIN-CTR UMIN000003662 ctr.cgi?function = brows&action = brows&type = summary&recptno = R000004436&language = J.

To investigate the combined and separate effects of exercise and milk fat globule membrane (MFGM) supplementation on frailty, physical function, physical activity level, and hematological parameters in community-dwelling elderly Japanese women. A total of 131 frail, elderly women over 75 years were randomly assigned to one of four groups: exercise and MFGM supplementation (Ex+MFGM), exercise and placebo (Ex+Plac), MFGM supplementation, or the placebo group. The exercise group attended a 60-minute training program twice a week for three months, and the MFGM group ingested 1g of the MFGM supplement in pill form, daily for 3 months. The primary outcome measure was change in frailty status based on Fried's frailty phenotype. Secondary outcome measures included body composition, physical function and hematological parameters, and interview survey components assessing lifestyle factors. Participants were followed for 4 months post-intervention. Significant group × time interactions were observed for usual walking speed (P = 0.005), timed up & go (P<0.001), and insulin-like growth factor-binding protein 3/insulin-like growth factor 1 ratio (P = 0.013). The frailty components revealed that weight loss, exhaustion, low physical activity, and slow walking speed were reversed, but low muscle strength did not significantly changed. Frailty reversal rate was significantly higher in the Ex+MFGM (57.6%) than in the MFGM (28.1%) or placebo (30.3%) groups at post-intervention (χ2 = 8.827, P = 0.032), and at the follow-up was also significantly greater in the Ex+MFGM (45.5%) and Ex+Plac (39.4%) groups compared with the placebo (15.2%) group (χ2 = 8.607, P = 0.035). The exercise+MFGM group had the highest odds ratio (OR) for frailty reversal at post-intervention and follow-up (OR = 3.12, 95% confidence interval (CI) = 1.13-8.60; and OR = 4.67, 95% CI = 1.45-15.08, respectively). This study suggests that interventions including exercise and nutrition can improve frailty status. Statistically significant additive effects of MFGM with exercise could not be confirmed in this population, and further investigation in larger samples is necessary. The Japan Medical Association Clinical Trial Registry (JMACCT)JMA-IIA00069.