2,187 research outputs found

    Blood methylomic signatures of presymptomatic dementia in elderly subjects with type 2 diabetes mellitus

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    Author version of article. The version of record is avilable from the publisher via doi: doi:10.1016/j.neurobiolaging.2014.12.023. Copyright © 2015 Elsevier Inc. All rights reserved.Available online 24 December 2014Due to an aging population, the incidence of dementia is steadily rising. The ability to identify early markers in blood, which appear before the onset of clinical symptoms is of considerable interest to allow early intervention, particularly in "high risk" groups such as those with type 2 diabetes. Here, we present a longitudinal study of genome-wide DNA methylation in whole blood from 18 elderly individuals with type 2 diabetes who developed presymptomatic dementia within an 18-month period following baseline assessment and 18 age-, sex-, and education-matched controls who maintained normal cognitive function. We identified a significant overlap in methylomic differences between groups at baseline and follow-up, with 8 CpG sites being consistently differentially methylated above our nominal significance threshold before symptoms at baseline and at 18 months follow up, after a diagnosis of presymptomatic dementia. Finally, we report a significant overlap between DNA methylation differences identified in converters, only after they develop symptoms of dementia, with differences at the same loci in blood samples from patients with clinically diagnosed Alzheimer's disease compared with unaffected control subjects.National Institute for Health Research (NIHR)Helen Bader FoundationLeroy Schecter FoundationBrightFocus Foundatio

    Suspension and Measurement of Graphene and Bi2Se3 Atomic Membranes

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    Coupling high quality, suspended atomic membranes to specialized electrodes enables investigation of many novel phenomena, such as spin or Cooper pair transport in these two dimensional systems. However, many electrode materials are not stable in acids that are used to dissolve underlying substrates. Here we present a versatile and powerful multi-level lithographical technique to suspend atomic membranes, which can be applied to the vast majority of substrate, membrane and electrode materials. Using this technique, we fabricated suspended graphene devices with Al electrodes and mobility of 5500 cm^2/Vs. We also demonstrate, for the first time, fabrication and measurement of a free-standing thin Bi2Se3 membrane, which has low contact resistance to electrodes and a mobility of >~500 cm^2/Vs

    A newly discovered subglacial lake in East Antarctica likely hosts a valuable sedimentary record of ice and climate change

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    The Princess Elizabeth Land sector of the East Antarctic Ice Sheet is a significant reservoir of grounded ice and is adjacent to regions that experienced great change during Quaternary glacial cycles and Pliocene warm episodes. The existence of an extensive subglacial water system in Princess Elizabeth Land (to date only inferred from satellite imagery) bears the potential to significantly impact the thermal and kinematic conditions of the overlying ice sheet. We confirm the existence of a major subglacial lake, herein referred to as Lake Snow Eagle (LSE), for the first time using recently acquired aerogeophysical data. We systematically investigated LSE’s geological characteristics and bathymetry from two-dimensional geophysical inversion models. The inversion results suggest that LSE is located along a compressional geologic boundary, which provides reference for future characterization of the geologic and tectonic context of this region. We estimate LSE to be ~42 km in length and 370 km2 in area, making it one of the largest subglacial lakes in Antarctica. Additionally, the airborne ice-penetrating radar observations and geophysical inversions reveal a layer of unconsolidated water-saturated sediment around and at the bottom of LSE, which—given the ultralow rates of sedimentation expected in such environments—may archive valuable records of paleoenvironmental changes and the early history of East Antarctic Ice Sheet evolution in Princess Elizabeth Land

    Sample Size Requirements for Studies of Treatment Effects on Beta-Cell Function in Newly Diagnosed Type 1 Diabetes

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    Preservation of -cell function as measured by stimulated C-peptide has recently been accepted as a therapeutic target for subjects with newly diagnosed type 1 diabetes. In recently completed studies conducted by the Type 1 Diabetes Trial Network (TrialNet), repeated 2-hour Mixed Meal Tolerance Tests (MMTT) were obtained for up to 24 months from 156 subjects with up to 3 months duration of type 1 diabetes at the time of study enrollment. These data provide the information needed to more accurately determine the sample size needed for future studies of the effects of new agents on the 2-hour area under the curve (AUC) of the C-peptide values. The natural log(), log(+1) and square-root transformations of the AUC were assessed. In general, a transformation of the data is needed to better satisfy the normality assumptions for commonly used statistical tests. Statistical analysis of the raw and transformed data are provided to estimate the mean levels over time and the residual variation in untreated subjects that allow sample size calculations for future studies at either 12 or 24 months of follow-up and among children 8–12 years of age, adolescents (13–17 years) and adults (18+ years). The sample size needed to detect a given relative (percentage) difference with treatment versus control is greater at 24 months than at 12 months of follow-up, and differs among age categories. Owing to greater residual variation among those 13–17 years of age, a larger sample size is required for this age group. Methods are also described for assessment of sample size for mixtures of subjects among the age categories. Statistical expressions are presented for the presentation of analyses of log(+1) and transformed values in terms of the original units of measurement (pmol/ml). Analyses using different transformations are described for the TrialNet study of masked anti-CD20 (rituximab) versus masked placebo. These results provide the information needed to accurately evaluate the sample size for studies of new agents to preserve C-peptide levels in newly diagnosed type 1 diabetes

    Gemini Planet Imager Observational Calibrations VI: Photometric and Spectroscopic Calibration for the Integral Field Spectrograph

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    The Gemini Planet Imager (GPI) is a new facility instrument for the Gemini Observatory designed to provide direct detection and characterization of planets and debris disks around stars in the solar neighborhood. In addition to its extreme adaptive optics and corona graphic systems which give access to high angular resolution and high-contrast imaging capabilities, GPI contains an integral field spectrograph providing low resolution spectroscopy across five bands between 0.95 and 2.5 μ\mum. This paper describes the sequence of processing steps required for the spectro-photometric calibration of GPI science data, and the necessary calibration files. Based on calibration observations of the white dwarf HD 8049B we estimate that the systematic error in spectra extracted from GPI observations is less than 5%. The flux ratio of the occulted star and fiducial satellite spots within coronagraphic GPI observations, required to estimate the magnitude difference between a target and any resolved companions, was measured in the HH-band to be Δm=9.23±0.06\Delta m = 9.23\pm0.06 in laboratory measurements and Δm=9.39±0.11\Delta m = 9.39\pm 0.11 using on-sky observations. Laboratory measurements for the YY, JJ, K1K1 and K2K2 filters are also presented. The total throughput of GPI, Gemini South and the atmosphere of the Earth was also measured in each photometric passband, with a typical throughput in HH-band of 18% in the non-coronagraphic mode, with some variation observed over the six-month period for which observations were available. We also report ongoing development and improvement of the data cube extraction algorithm.Comment: 15 pages, 6 figures. Proceedings of the SPIE, 9147-30

    Football in the community schemes: Exploring the effectiveness of an intervention in promoting healthful behaviour change

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    This study aims to examine the effectiveness of a Premier League football club’s Football in the Community (FitC) schemes intervention in promoting positive healthful behaviour change in children. Specifically, exploring the effectiveness of this intervention from the perspectives of the participants involved (i.e. the researcher, teachers, children and coaches). A range of data collection techniques were utilized including the principles of ethnography (i.e. immersion, engagement and observations), alongside conducting focus groups with the children. The results allude to the intervention merely ‘keeping active children active’ via (mostly) fun, football sessions. Results highlight the important contribution the ‘coach’ plays in the effectiveness of the intervention. Results relating to working practice (i.e. coaching practice and coach recruitment) are discussed and highlighted as areas to be addressed. FitC schemes appear to require a process of positive organizational change to increase their effectiveness in strategically attending to the health agenda
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