Autonomic Cluster Management System (ACMS): A Demonstration of Autonomic Principles at Work

Cluster computing, whereby a large number of simple processors or nodes are combined together to apparently function as a single powerful computer, has emerged as a research area in its own right. The approach offers a relatively inexpensive means of achieving significant computational capabilities for high-performance computing applications, while simultaneously affording the ability to. increase that capability simply by adding more (inexpensive) processors. However, the task of manually managing and con.guring a cluster quickly becomes impossible as the cluster grows in size. Autonomic computing is a relatively new approach to managing complex systems that can potentially solve many of the problems inherent in cluster management. We describe the development of a prototype Automatic Cluster Management System (ACMS) that exploits autonomic properties in automating cluster management

Middle Fossa Extension of Posterior Fossa Meningiomas is Associated with Poorer Clinical Outcomes

Introduction: Progression of posterior fossa meningiomas (PFMs) can lead to extension into the middle cranial fossa. Pre-operative imaging allows for quantification of middle fossa extension (MFE). We aimed to determine the clinical impact of MFE on surgical and clinical outcomes during resection of PFMs. Methods: Craniotomies for meningiomas performed at a large single center academic institution from January 2012 to December 2018 were identified. Preoperative MRI and CT imaging was reviewed to determine the presence of MFE of posterior fossa meningiomas and correlated to post-operative outcomes. Results: 65 PFMs were identified and mean follow-up was 28.8 ± 20.1 months. 13/65 PFMs showed MFE preoperatively. Average size of PFMs with MFE (36.1 cm ± 12.1 cm) was similar to PFMs without MFE (33.5 cm ± 9.2 cm, p \u3e 0.05). 9/13 PFMs with MFE were petrous or petroclival, and 4/13 involved the cavernous sinus. Retrosigmoid craniotomy was the most utilized approach for both isolated PFMs (51.9%) and PFMs with MFE (76.9%). Anterior approaches were used in 2/13 PFMs with MFE. Presence of MFE was strongly associated with decreased rates of GTR (RR= 0.1; p \u3c 0.05). MFE wasn’t associated with longer LOS or rates of readmission within 30 days of discharge, but was associated with a significantly higher rate of overall mortality at last follow-up (RR=5.3; 95%; p \u3c 0.05). Conclusion: PFMs with MFE are easily identifiable and are associated with decreased rates of GTR and overall prognosis and may suggest the need for anterior or combined approaches

Genetic analyses of the electrocardiographic QT interval and its components identify additional loci and pathways

The QT interval is an electrocardiographic measure representing the sum of ventricular depolarization and repolarization, estimated by QRS duration and JT interval, respectively. QT interval abnormalities are associated with potentially fatal ventricular arrhythmia. Using genome-wide multi-ancestry analyses (>250,000 individuals) we identify 177, 156 and 121 independent loci for QT, JT and QRS, respectively, including a male-specific X-chromosome locus. Using gene-based rare-variant methods, we identify associations with Mendelian disease genes. Enrichments are observed in established pathways for QT and JT, and previously unreported genes indicated in insulin-receptor signalling and cardiac energy metabolism. In contrast for QRS, connective tissue components and processes for cell growth and extracellular matrix interactions are significantly enriched. We demonstrate polygenic risk score associations with atrial fibrillation, conduction disease and sudden cardiac death. Prioritization of druggable genes highlight potential therapeutic targets for arrhythmia. Together, these results substantially advance our understanding of the genetic architecture of ventricular depolarization and repolarization

Design and Evaluation of a Public Resource Computing Framework

Public resource computing (PRC) is an innovative approach to high performance computing that relies on volunteers who donate their personal computers’ unused resources to a computationally intensive research project. Prominent PRC projects include SETI@home, Folding@Home, and distributed.net. Many PRC projects are built upon a PRC framework that abstracts functionality that is common to all PRC projects, such as network communications, database access, and project management. These PRC frameworks tend to be complex, limiting, and difficult to use. We have designed and implemented a new PRC framework called the Simple Light-weight Infrastructure for Network Computing (SLINC) that addresses the disadvantages we identified with existing frameworks. SLINC is a flexible and extensible PRC framework that will enable researchers to more easily build PRC projects

Gaseous air pollutants and DNA methylation in a methylome-wide association study of an ethnically and environmentally diverse population of U.S. adults

Epigenetic mechanisms may underlie air pollution-health outcome associations. We estimated gaseous air pollutant-DNA methylation (DNAm) associations using twelve subpopulations within Women's Health Initiative (WHI) and Atherosclerosis Risk in Communities (ARIC) cohorts (n = 8397; mean age 61.3 years; 83% female; 46% African-American, 46% European-American, 8% Hispanic/Latino). We used geocoded participant address-specific mean ambient carbon monoxide (CO), nitrogen oxides (NO2; NOx), ozone (O3), and sulfur dioxide (SO2) concentrations estimated over the 2-, 7-, 28-, and 365-day periods before collection of blood samples used to generate Illumina 450 k array leukocyte DNAm measurements. We estimated methylome-wide, subpopulation- and race/ethnicity-stratified pollutant-DNAm associations in multi-level, linear mixed-effects models adjusted for sociodemographic, behavioral, meteorological, and technical covariates. We combined stratum-specific estimates in inverse variance-weighted meta-analyses and characterized significant associations (false discovery rate; FDR 0.05). We attempted replication in the Cooperative Health Research in Region of Augsburg (KORA) study and Normative Aging Study (NAS). We observed a -0.3 (95% CI: -0.4, -0.2) unit decrease in percent DNAm per interquartile range (IQR, 7.3 ppb) increase in 28-day mean NO2 concentration at cg01885635 (chromosome 3; regulatory region 290 bp upstream from ZNF621; FDR = 0.03). At intragenic sites cg21849932 (chromosome 20; LIME1; intron 3) and cg05353869 (chromosome 11; KLHL35; exon 2), we observed a -0.3 (95% CI: -0.4, -0.2) unit decrease (FDR = 0.04) and a 1.2 (95% CI: 0.7, 1.7) unit increase (FDR = 0.04), respectively, in percent DNAm per IQR (17.6 ppb) increase in 7-day mean ozone concentration. Results were not fully replicated in KORA and NAS. We identified three CpG sites potentially susceptible to gaseous air pollution-induced DNAm changes near genes relevant for cardiovascular and lung disease. Further harmonized investigations with a range of gaseous pollutants and averaging durations are needed to determine the effect of gaseous air pollutants on DNA methylation and ultimately gene expression