The Effect of Alcohol Consumption on Brain Ageing: A New Causal Inference Framework for Incomplete and Massive Phenomic Data

Although substance use, such as alcohol consumption, is known to be associated with cognitive decline during ageing, its direct influence on the central nervous system remains unclear. In this study, we aim to investigate the potential influence of alcohol intake frequency on accelerated brain ageing by estimating the mean potential brain-age gap (BAG) index, the difference between brain age and actual age, under different alcohol intake frequencies in a large UK Biobank (UKB) cohort with extensive phenomic data reflecting a comprehensive life-style profile. We face two major challenges: (1) a large number of phenomic variables as potential confounders and (2) a small proportion of participants with complete phenomic data. To address these challenges, we first develop a new ensemble learning framework to establish robust estimation of mean potential outcome in the presence of many confounders. We then construct a data integration step to borrow information from UKB participants with incomplete phenomic data to improve efficiency. Our analysis results reveal that daily intake or even a few times a week may have significant effects on accelerating brain ageing. Moreover, extensive numerical studies demonstrate the superiority of our method over competing methods, in terms of smaller estimation bias and variability.Comment: Contact: [email protected]

Bubble Dynamics in a Narrow Rectangular Channel

It is very important to study the bubble dynamics in order to understand the physical process of boiling heat transfer in a narrow channel. Experimental and theoretical studies on bubble dynamics in a narrow rectangular channel are proposed. The cross section of the narrow rectangular channel is 2 mm × 8 mm. A high speed digital camera is applied to capture bubble behaviors from the narrow side and wide side of the narrow rectangular channel. Bubble growth rate, bubble departure diameter, bubble interface parameter and others are obtained according to the observation. A force balance analysis on a growing bubble is proposed to predict the bubble departure diameter and sliding bubble velocity, and the predicted results agree with the experimental data. Thus, the mechanism of bubble departure, slide and lift-off behavior in a narrow rectangular channel can be explained by the analysis of forces

Bhs: An Novel Scheduling Strategy on Modern Processors

AbstractIn order to design a faster CPU, it is becoming more and more complex on the CPU architecture. But many-core is incompatible with the current programming mode designed for single-core CPU. This paper proposes a Block level Hardware-based Scheduling (BHS) on many-core architecture. The two main features are: First, design and implement a block-based hardware scheduler to reduce the overhead of threads, and to get a faster communication between processing units; second, it is very applicable to small and scalable cores on many-core architecture that is tightly coupled in the cores group, loosely coupled between groups. And a variety of parallel techniques would effectively exploit

Evaluating the causal effect of tobacco smoking on white matter brain aging: a two-sample Mendelian randomization analysis in UK Biobank.

BACKGROUND AND AIMS: Tobacco smoking is a risk factor for impaired brain function, but its causal effect on white matter brain aging remains unclear. This study aimed to measure the causal effect of tobacco smoking on white matter brain aging. DESIGN: Mendelian randomization (MR) analysis using two non-overlapping data sets (with and without neuroimaging data) from UK Biobank (UKB). The group exposed to smoking and control group consisted of current smokers and never smokers, respectively. Our main method was generalized weighted linear regression with other methods also included as sensitivity analysis. SETTING: United Kingdom. PARTICIPANTS: The study cohort included 23 624 subjects [10 665 males and 12 959 females with a mean age of 54.18 years, 95% confidence interval (CI) = 54.08, 54.28]. MEASUREMENTS: Genetic variants were selected as instrumental variables under the MR analysis assumptions: (1) associated with the exposure; (2) influenced outcome only via exposure; and (3) not associated with confounders. The exposure smoking status (current versus never smokers) was measured by questionnaires at the initial visit (2006-10). The other exposure, cigarettes per day (CPD), measured the average number of cigarettes smoked per day for current tobacco users over the life-time. The outcome was the \u27brain age gap\u27 (BAG), the difference between predicted brain age and chronological age, computed by training machine learning model on a non-overlapping set of never smokers. FINDINGS: The estimated BAG had a mean of 0.10 (95% CI = 0.06, 0.14) years. The MR analysis showed evidence of positive causal effect of smoking behaviors on BAG: the effect of smoking is 0.21 (in years, 95% CI = 6.5 × 10 CONCLUSIONS: There appears to be a significant causal effect of smoking on the brain age gap, which suggests that smoking prevention can be an effective intervention for accelerated brain aging and the age-related decline in cognitive function

Comparing empirical kinship derived heritability for imaging genetics traits in the UK biobank and human connectome project

Imaging genetics analyses use neuroimaging traits as intermediate phenotypes to infer the degree of genetic contribution to brain structure and function in health and/or illness. Coefficients of relatedness (CR) summarize the degree of genetic similarity among subjects and are used to estimate the heritability – the proportion of phenotypic variance explained by genetic factors. The CR can be inferred directly from genome-wide genotype data to explain the degree of shared variation in common genetic polymorphisms (SNP-heritability) among related or unrelated subjects. We developed a central processing and graphics processing unit (CPU and GPU) accelerated Fast and Powerful Heritability Inference (FPHI) approach that linearizes likelihood calculations to overcome the ∼N2–3 computational effort dependency on sample size of classical likelihood approaches. We calculated for 60 regional and 1.3 × 105 voxel-wise traits in N = 1,206 twin and sibling participants from the Human Connectome Project (HCP) (550 M/656 F, age = 28.8 ± 3.7 years) and N = 37,432 (17,531 M/19,901 F; age = 63.7 ± 7.5 years) participants from the UK Biobank (UKBB). The FPHI estimates were in excellent agreement with heritability values calculated using Genome-wide Complex Trait Analysis software (r = 0.96 and 0.98 in HCP and UKBB sample) while significantly reducing computational (102–4 times). The regional and voxel-wise traits heritability estimates for the HCP and UKBB were likewise in excellent agreement (r = 0.63–0.76, p \u3c 10−10). In summary, the hardware-accelerated FPHI made it practical to calculate heritability values for voxel-wise neuroimaging traits, even in very large samples such as the UKBB. The patterns of additive genetic variance in neuroimaging traits measured in a large sample of related and unrelated individuals showed excellent agreement regardless of the estimation method. The code and instruction to execute these analyses are available at www.solar-eclipse-genetics.org

Brain-Wide Versus Genome-Wide Vulnerability Biomarkers for Severe Mental Illnesses

Severe mental illnesses (SMI), including major depressive (MDD), bipolar (BD), and schizophrenia spectrum (SSD) disorders have multifactorial risk factors and capturing their complex etiopathophysiology in an individual remains challenging. Regional vulnerability index (RVI) was used to measure individual\u27s brain‐wide similarity to the expected SMI patterns derived from meta‐analytical studies. It is analogous to polygenic risk scores (PRS) that measure individual\u27s similarity to genome‐wide patterns in SMI. We hypothesized that RVI is an intermediary phenotype between genome and symptoms and is sensitive to both genetic and environmental risks for SMI. UK Biobank sample of N = 17,053/19,265 M/F (age = 64.8 ± 7.4 years) and an independent sample of SSD patients and controls (N = 115/111 M/F, age = 35.2 ± 13.4) were used to test this hypothesis. UKBB participants with MDD had significantly higher RVI‐MDD (Cohen\u27s d = 0.20, p = 1 × 10−23) and PRS‐MDD (d = 0.17, p = 1 × 10−15) than nonpsychiatric controls. UKBB participants with BD and SSD showed significant elevation in the respective RVIs (d = 0.65 and 0.60; p = 3 × 10−5 and .009, respectively) and PRS (d = 0.57 and 1.34; p = .002 and .002, respectively). Elevated RVI‐SSD were replicated in an independent sample (d = 0.53, p = 5 × 10−5). RVI‐MDD and RVI‐SSD but not RVI‐BD were associated with childhood adversity (p \u3c .01). In nonpsychiatric controls, elevation in RVI and PRS were associated with lower cognitive performance (p \u3c 10−5) in six out of seven domains and showed specificity with disorder‐associated deficits. In summary, the RVI is a novel brain index for SMI and shows similar or better specificity for SMI than PRS, and together they may complement each other in the efforts to characterize the genomic to brain level risks for SMI

Elevated Blood Pressure Accelerates White Matter Brain Aging Among Late Middle-Aged Women: A Mendelian Randomization Study in the UK Biobank

BACKGROUND: Elevated blood pressure (BP) is a modifiable risk factor associated with cognitive impairment and cerebrovascular diseases. However, the causal effect of BP on white matter brain aging remains unclear. METHODS: In this study, we focused on N  = 228 473 individuals of European ancestry who had genotype data and clinical BP measurements available (103 929 men and 124 544 women, mean age = 56.49, including 16 901 participants with neuroimaging data available) collected from UK Biobank (UKB). We first established a machine learning model to compute the outcome variable brain age gap (BAG) based on white matter microstructure integrity measured by fractional anisotropy derived from diffusion tensor imaging data. We then performed a two-sample Mendelian randomization analysis to estimate the causal effect of BP on white matter BAG in the whole population and subgroups stratified by sex and age brackets using two nonoverlapping data sets. RESULTS: The hypertension group is on average 0.31 years (95% CI = 0.13-0.49; P  \u3c 0.0001) older in white matter brain age than the nonhypertension group. Women are on average 0.81 years (95% CI = 0.68-0.95; P  \u3c 0.0001) younger in white matter brain age than men. The Mendelian randomization analyses showed an overall significant positive causal effect of DBP on white matter BAG (0.37 years/10 mmHg, 95% CI 0.034-0.71, P  = 0.0311). In stratified analysis, the causal effect was found most prominent among women aged 50-59 and aged 60-69. CONCLUSION: High BP can accelerate white matter brain aging among late middle-aged women, providing insights on planning effective control of BP for women in this age group

An Implementation of Power-aware Storage Architecture

Nowadays, large storage is becoming an important feature of mobile embedded systems as their media functions are getting increasingly powerful and popular. However, no low power cost memory can provide sufficient capacity at low cost. And much higher power consumption of large capacity storage devices such as Microdrive is hard to be accepted. In this paper, we propose a logical storage layer over hybrid storage device composed of flash memory and Microdrive to provide file systems to embedded systems with minimal impact on battery runtime and power consumption. The result shows that the architecture can provide 32 times as much capacity with 10-15 % battery runtime impact