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64) compared with cardiac death. Individuals with iMVP had larger mitral valve annulus compared with noncardiac death (121 versus 108 mm; P less then 0.001) and cardiac death (121 versus 110 mm; P=0.002), and more left ventricular fibrosis (79% versus 38%; P less then 0.001) compared with noncardiac death controls. In those with iMVP and witnessed cardiac arrest, 94% had ventricular fibrillation. Conclusions Individuals with iMVP and sudden death have increased cardiac mass, mitral annulus size, and left ventricular fibrosis compared with a matched cohort, with cardiac arrest caused by ventricular fibrillation. The histopathological changes in iMVP may provide the substrate necessary for development of malignant ventricular arrhythmias.Background Previous studies reported that early-life exposure to undernutrition is associated with the risk of diabetes mellitus and metabolic syndrome in adulthood, but the association with risk of cardiovascular disease (CVD) later in life remains unclear. The current study aimed to investigate whether exposure to Chinese famine in early life is associated with risk of CVD. Methods and Results We used data from REACTION (Risk Evaluation of Cancers in Chinese Diabetic Individuals A Longitudinal Study), which recruited a total of 259 657 community-dwelling adults aged 40 years or older from 25 centers across mainland China between 2011 and 2012. Compared with the nonexposed participants, those who had been exposed to famine in early life had a significantly increased risk of total CVD, myocardial infarction, stroke, and coronary heart disease. In the multivariable-adjusted logistic regression model, the odds ratios (95% CI) for total CVD, myocardial infarction, stroke, and coronary heart disease in fetal famine exposure were 1.35 (1.20-1.52), 1.59 (1.08-2.35), 1.40 (1.11-1.78), and 1.44 (1.26-1.65), respectively; those odds ratios in childhood famine exposure were 1.59 (1.40-1.81), 2.20 (1.52-3.20), 1.82 (1.45-2.28), and 1.80 (1.56-2.09), respectively; and those in adolescent famine exposure were 1.52 (1.27-1.81), 2.07 (1.28-3.35), 1.92 (1.42-2.58), and 1.83 (1.50-2.24), respectively. The main finding of our study is that, compared with those who lived in the less severely affected famine area, individuals in the severely affected famine area had significantly increased risk of total CVD in all 3 exposed groups. Conclusions Early-life exposure to undernutrition is associated with significantly increased risk of CVD in later life, especially among those who were in the severely affected famine area.The discovery of new biomarkers would be very valuable to improve the detection of early Alzheimer's disease (AD). DNA methylation marks may serve as epigenetic biomarkers of early AD. Here we identified epigenetic marks that are present in the human hippocampus from the earliest stages of AD. A previous methylome dataset of the human AD hippocampus was used to select a set of eight differentially methylated positions (DMPs) since early AD stages. Next, bisulphite pyrosequencing was performed in an expanded homogeneous cohort of 18 pure controls and 35 hippocampal samples with neuropathological changes of pure AD. Correlation between DNA methylation levels in DMPs and phospho-tau protein burden assessed by immunohistochemistry in the hippocampus was also determined. We found four DMPs showing higher levels of DNA methylation at early AD stages compared to controls, involving ELOVL2, GIT1/TP53I13 and the histone gene locus at chromosome 6. DNA methylation levels assessed by bisulphite pyrosequencing correlated with phospho-tau protein burden for ELOVL2 and HIST1H3E/HIST1H3 F genes. In this discovery study, a set of four epigenetic marks of early AD stages have been identified in the human hippocampus. It would be worth studying in-depth the specific pathways related to these epigenetic marks. These early alterations in DNA methylation in the AD hippocampus could be regarded as candidate biomarkers to be explored in future translational studies.Abbreviations AD Alzheimer's disease; DMPs Differentially methylated positions; CSF Cerebrospinal fluid; βA42 β-amyloid 42; PET positron emission tomography; 5mC 5-methyl cytosine; CpG cytosine-guanine dinucleotides; ANK1 ankyrin-1; BIN1 amphiphysin II; p-tau hyperphosphorylated tau; CERAD Consortium to Establish A Registry for Alzheimer's Disease; SD standard deviation; ANOVA one-way analysis of variance; VLCFAs very long-chain fatty acids; DHA docosahexaenoic acid; mTOR mechanistic target of rapamycin.The quality of vehicular collision data is crucial for studying the relationship between injury severity and collision factors. Misclassified injury severity data in the crash dataset, however, may cause inaccurate parameter estimates and consequently lead to biased conclusions and poorly designed countermeasures. This is particularly true for imbalanced data where the number of samples in one class far outnumber the other. To improve the classification performance of the injury severity, the paper presents a robust noise filtering technique to deal with the mislabels in the imbalanced crash dataset using the advanced machine learning algorithms. We examine the state-of-the-art filtering algorithms, including Iterative Noise Filtering based on the Fusion of Classifiers (INFFC), Iterative Partitioning Filter (IPF), and Saturation Filter (SatF). TAK-242 molecular weight In the case study of Cairo (Egypt), the empirical results show that (1) the mislabels in crash data significantly influence the injury severity predictions, and (2) the proposed M-IPF filter outperforms its counterparts in terms of the effectiveness and efficiency in eliminating the mislabels in crash data. The test results demonstrate the efficacy of the M-IPF in handling the data noise and mitigating the impacts thereof.The loss of a significant other often creates emotional distress for family members that can hamper the ability to meet everyday challenges and pursue wellness. The aim of this qualitative study was to understand the challenge of losing a significant other for older adult family members and the approaches identified as most helpful to promote their own well-being after this person dies. Story inquiry method guided the interview process with 15 older adult bereaved family members residing in a continuing care retirement community. Theory-guided content analysis was used for data analysis. Two themes described the challenges uneasiness that permeates everyday living and precious memories and patterns of disconnect that breed discontent. Appreciating the rhythmic flow of everyday connecting and separating and embracing reality as situated in one's lifelong journey are the themes that encompass the helpful approaches used by participants. This study provided insights about the benefits of living in this community such as social networking and a possible drawback such as the frequency of death among residents.