Indoor air quality measurements in energy efficient buildings

The Energy Efficient Buildings Program of the Lawrence Berkeley Laboratory (LBL) has designed and fabricated a mobile laboratory for research and development studies of ventilation requirements and energy utilization in residential and commercial buildings. The Energy Efficient Buildings (EEB) Mobile Laboratory is used in studies of indoor air quality in buildings before and after energy conservation retrofits and in new buildings incorporating energy efficient designs. Indoor air quality measurements have been conducted in residential buildings and work in progress includes indoor air quality monitoring in schools, hospitals, and energy efficient residential buildings. The monitoring program includes measurement of CO, CO/sub 2/, SO/sub 2/, NO, NO/sub 2/, O/sub 3/, infiltration rate (tracer gas technique), and aerosol size distribution on a continuous basis. Total and respirable-fraction particulate samples are collected on membrane filter media for analysis by x-ray fluorescence (XRFA), photoelectron spectroscopy (ESCA), proton activation analysis (PAA), combustion, and wet-chemistry techniques for the determination of particulate elemental composition (S, N, C, etc.) and ionic species such as SO/sub 4//sup 2 -/, NO/sub 3//sup -/, and NH/sub 4//sup +/. Results of the initial phases of this program indicate that the concentrations of some gaseous and respirable particulate air pollutants in specific indoor environments exceed those levels commonly found in the outdoor urban air environment

Genome-wide Analyses Identify KIF5A as a Novel ALS Gene

To identify novel genes associated with ALS, we undertook two lines of investigation. We carried out a genome-wide association study comparing 20,806 ALS cases and 59,804 controls. Independently, we performed a rare variant burden analysis comparing 1,138 index familial ALS cases and 19,494 controls. Through both approaches, we identified kinesin family member 5A (KIF5A) as a novel gene associated with ALS. Interestingly, mutations predominantly in the N-terminal motor domain of KIF5A are causative for two neurodegenerative diseases: hereditary spastic paraplegia (SPG10) and Charcot-Marie-Tooth type 2 (CMT2). In contrast, ALS-associated mutations are primarily located at the C-terminal cargo-binding tail domain and patients harboring loss-of-function mutations displayed an extended survival relative to typical ALS cases. Taken together, these results broaden the phenotype spectrum resulting from mutations in KIF5A and strengthen the role of cytoskeletal defects in the pathogenesis of ALS.Peer reviewe

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

The transcriptional landscape of age in human peripheral blood

Disease incidences increase with age, but the molecular characteristics of ageing that lead to increased disease susceptibility remain inadequately understood. Here we perform a whole-blood gene expression meta-analysis in 14,983 individuals of European ancestry (including replication) and identify 1,497 genes that are differentially expressed with chronological age. The age-associated genes do not harbor more age-associated CpG-methylation sites than other genes, but are instead enriched for the presence of potentially functional CpG-methylation sites in enhancer and insulator regions that associate with both chronological age and gene expression levels. We further used the gene expression profiles to calculate the 'transcriptomic age' of an individual, and show that differences between transcriptomic age and chronological age are associated with biological features linked to ageing, such as blood pressure, cholesterol levels, fasting glucose, and body mass index. The transcriptomic prediction model adds biological relevance and complements existing epigenetic prediction models, and can be used by others to calculate transcriptomic age in external cohorts.Peer reviewe

Genome sequencing analysis identifies new loci associated with Lewy body dementia and provides insights into its genetic architecture

The genetic basis of Lewy body dementia (LBD) is not well understood. Here, we performed whole-genome sequencing in large cohorts of LBD cases and neurologically healthy controls to study the genetic architecture of this understudied form of dementia, and to generate a resource for the scientific community. Genome-wide association analysis identified five independent risk loci, whereas genome-wide gene-aggregation tests implicated mutations in the gene GBA. Genetic risk scores demonstrate that LBD shares risk profiles and pathways with Alzheimer's disease and Parkinson's disease, providing a deeper molecular understanding of the complex genetic architecture of this age-related neurodegenerative condition