Frequency of the C9orf72 hexanucleotide repeat expansion in patients with amyotrophic lateral sclerosis and frontotemporal dementia: a cross-sectional study.

We aimed to accurately estimate the frequency of a hexanucleotide repeat expansion in C9orf72 that has been associated with a large proportion of cases of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD)

Data Descriptor: A global multiproxy database for temperature reconstructions of the Common Era

Reproducible climate reconstructions of the Common Era (1 CE to present) are key to placing industrial-era warming into the context of natural climatic variability. Here we present a community-sourced database of temperature-sensitive proxy records from the PAGES2k initiative. The database gathers 692 records from 648 locations, including all continental regions and major ocean basins. The records are from trees, ice, sediment, corals, speleothems, documentary evidence, and other archives. They range in length from 50 to 2000 years, with a median of 547 years, while temporal resolution ranges from biweekly to centennial. Nearly half of the proxy time series are significantly correlated with HadCRUT4.2 surface temperature over the period 1850-2014. Global temperature composites show a remarkable degree of coherence between high-and low-resolution archives, with broadly similar patterns across archive types, terrestrial versus marine locations, and screening criteria. The database is suited to investigations of global and regional temperature variability over the Common Era, and is shared in the Linked Paleo Data (LiPD) format, including serializations in Matlab, R and Python.(TABLE)Since the pioneering work of D'Arrigo and Jacoby1-3, as well as Mann et al. 4,5, temperature reconstructions of the Common Era have become a key component of climate assessments6-9. Such reconstructions depend strongly on the composition of the underlying network of climate proxies10, and it is therefore critical for the climate community to have access to a community-vetted, quality-controlled database of temperature-sensitive records stored in a self-describing format. The Past Global Changes (PAGES) 2k consortium, a self-organized, international group of experts, recently assembled such a database, and used it to reconstruct surface temperature over continental-scale regions11 (hereafter, ` PAGES2k-2013').This data descriptor presents version 2.0.0 of the PAGES2k proxy temperature database (Data Citation 1). It augments the PAGES2k-2013 collection of terrestrial records with marine records assembled by the Ocean2k working group at centennial12 and annual13 time scales. In addition to these previously published data compilations, this version includes substantially more records, extensive new metadata, and validation. Furthermore, the selection criteria for records included in this version are applied more uniformly and transparently across regions, resulting in a more cohesive data product.This data descriptor describes the contents of the database, the criteria for inclusion, and quantifies the relation of each record with instrumental temperature. In addition, the paleotemperature time series are summarized as composites to highlight the most salient decadal-to centennial-scale behaviour of the dataset and check mutual consistency between paleoclimate archives. We provide extensive Matlab code to probe the database-processing, filtering and aggregating it in various ways to investigate temperature variability over the Common Era. The unique approach to data stewardship and code-sharing employed here is designed to enable an unprecedented scale of investigation of the temperature history of the Common Era, by the scientific community and citizen-scientists alike

Stability of plasma analytes after delayed separation of whole blood: implications for epidemiological studies.

BACKGROUND: Large blood-based epidemiological studies require simple, cost-effective sample collection methods. Immediate sample separation or rapid transport of chilled blood samples to a central laboratory may be impractical or prohibitively expensive. To assess the feasibility and reliability of transporting blood samples over several days at ambient temperature (e.g. by mail), we evaluated the stability of various plasma analytes in samples stored at room temperature or chilled. METHODS: Multiple vacutainers of blood, containing EDTA and aprotinin as preservative, were drawn from 12 volunteers and stored at 21 degrees C or 4 degrees C. Immediately after collection and 1, 2, 3, 4, and 7 days later, vacutainers stored at each temperature were centrifuged, and the plasma was aliquoted and stored at -80 degrees C. Subsequently, all aliquots from each individual were analysed in one analytical run for a range of chemistries. RESULTS: In whole blood stored at room temperature for up to 7 days, concentrations of albumin, apolipoproteins A1 and B (apoA1 and apoB), cholesterol, high density lipoprotein (HDL), total protein, and triglycerides changed by less than 4%, and low density lipoprotein (LDL) by less than 7%. Whilst alanine transaminase (ALT), creatine kinase (CK), creatinine, and gamma-glutamyl transferase (GGT) concentrations changed substantially at room temperature, there was less than 4% change during chilled storage up to 7 days. By contrast, aspartate transaminase (AST) concentrations increased markedly under both conditions. CONCLUSIONS: A wide range of important analytes, including lipids, change by only a few per cent in whole blood during storage at room temperature for several days. Mailed transport of whole blood samples may, therefore, be a simple and cost-effective option for large-scale epidemiological studies

Effect of temperature and light on the stability of fat-soluble vitamins in whole blood over several days: implications for epidemiological studies.

BACKGROUND: Biochemical measurement of fat-soluble vitamins would allow direct assessment in epidemiological studies of their association with disease. However, the perceived instability of these compounds and typically high cost of collection and analysis may make their measurement impractical, particularly in large-scale studies. Using a high performance liquid chromatography assay developed in-house, we have investigated the separate effects of temperature and light on the stability of vitamins in whole blood over several days. METHODS: Multiple blood samples from 10 volunteers were stored at 20 degrees C or 4 degrees C and in dark or light conditions. Immediately after collection and 1, 2, 3, 4, and 7 days later, samples stored under each condition were centrifuged, and the plasma was aliquoted and stored at -80 degrees C. Subsequently, all aliquots from each individual were analysed in one analytical run. RESULTS: In whole blood stored under any of the four conditions for up to 7 days, concentrations of alpha-carotene, beta-carotene, lutein, lycopene, retinol, and alpha-tocopherol changed by less than 8%, and cryptoxanthin and gamma-tocopherol by less than 11%. Although significant temperature effects were observed for alpha-carotene, and alpha- and gamma-tocopherol, and a significant effect of light was observed for alpha-carotene, cryptoxanthin, and lycopene, these analytes changed by less than 1% per day under all conditions. CONCLUSIONS: Concentrations of these fat-soluble vitamins change by only a few per cent in whole blood during storage at room temperature for several days. Hence, delayed separation of blood samples (which may be required for practical reasons in large-scale epidemiological studies) does not preclude reliable measurement of fat-soluble vitamins