1,072 research outputs found

    Too Immature to Vote?

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    This article argues in favour of lowering the voting age to 16. First, it outlines a respect-based account of democracy where the right to vote is grounded in a respect for citizens’ autonomous capacities. It then outlines a normative account of autonomy, modelled on Rawls’s two moral powers, saying what criteria must be met for an individual to possess a (pro tanto) moral right to vote. Second, it engages with empirical psychology to show that by the age of 16 (if not earlier) individuals h

    Cohabitation, infection and breast cancer risk.

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    For 50 years, the effect of age at first birth (AFB) has been thought to explain the strong association between breast cancer risk and age at first marriage (AFM), which was first reported in 1926. The independent effects of AFM, AFB and number of sexual partners adjusted for parity and other risk factors were estimated in reanalysis of a large international case-control study conducted in 1979 to 1982 (2274 breast cancers, 18209 controls) by unconditional logistic regression. Respective AFB and AFM breast cancer odds ratios (ORs) for ≥31 years relative to ≤18 years were 3.01 (95% CI 2.44-3.71; P(trend) < .0001) and 3.24 (95% CI 2.62-4.01; P(trend) < .0001) in univariate analyses. Among married parous women, these ORs fell to 1.38 (95% CI 0.98-1.95; P(trend) < .03) for AFB and 1.70 (95% CI 1.17-2.46; P(trend) < .002) for AFM when fitted together in multivariate analysis including other risk factors. A similar adjusted OR for AFM ≥ 31 years relative to ≤18 years was seen among married nulliparous women (OR 1.71, 95% CI 0.98-2.98; P(trend) < .001). AFM (a surrogate for age at starting prolonged cohabitation) is thus strongly associated with breast cancer risk. This suggests an effect of close contact. Identifying the (probably infective) mechanism might lead to effective prevention of breast cancer. The independent effect of AFB is smaller and could be due to residual confounding

    Evaluation of methods for detecting human reads in microbial sequencing datasets

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    Sequencing data from host-associated microbes can often be contaminated by the body of the investigator or research subject. Human DNA is typically removed from microbial reads either by subtractive alignment (dropping all reads that map to the human genome) or by using a read classification tool to predict those of human origin, and then discarding them. To inform best practice guidelines, we benchmarked eight alignment-based and two classification-based methods of human read detection using simulated data from 10 clinically prevalent bacteria and three viruses, into which contaminating human reads had been added. While the majority of methods successfully detected >99 % of the human reads, they were distinguishable by variance. The most precise methods, with negligible variance, were Bowtie2 and SNAP, both of which misidentified few, if any, bacterial reads (and no viral reads) as human. While correctly detecting a similar number of human reads, methods based on taxonomic classification, such as Kraken2 and Centrifuge, could misclassify bacterial reads as human, although the extent of this was species-specific. Among the most sensitive methods of human read detection was BWA, although this also made the greatest number of false positive classifications. Across all methods, the set of human reads not identified as such, although often representing 300 bp) bacterial reads, the highest performing approaches were classification-based, using Kraken2 or Centrifuge. For shorter (c. 150 bp) bacterial reads, combining multiple methods of human read detection maximized the recovery of human reads from contaminated short read datasets without being compromised by false positives. A particularly high-performance approach with shorter bacterial reads was a two-stage classification using Bowtie2 followed by SNAP. Using this approach, we re-examined 11 577 publicly archived bacterial read sets for hitherto undetected human contamination. We were able to extract a sufficient number of reads to call known human SNPs, including those with clinical significance, in 6 % of the samples. These results show that phenotypically distinct human sequence is detectable in publicly archived microbial read datasets

    Optical Coherence Tomography in the UK Biobank Study - Rapid Automated Analysis of Retinal Thickness for Large Population-Based Studies

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    PURPOSE: To describe an approach to the use of optical coherence tomography (OCT) imaging in large, population-based studies, including methods for OCT image acquisition, storage, and the remote, rapid, automated analysis of retinal thickness. METHODS: In UK Biobank, OCT images were acquired between 2009 and 2010 using a commercially available “spectral domain” OCT device (3D OCT-1000, Topcon). Images were obtained using a raster scan protocol, 6 mm x 6 mm in area, and consisting of 128 B-scans. OCT image sets were stored on UK Biobank servers in a central repository, adjacent to high performance computers. Rapid, automated analysis of retinal thickness was performed using custom image segmentation software developed by the Topcon Advanced Biomedical Imaging Laboratory (TABIL). This software employs dual-scale gradient information to allow for automated segmentation of nine intraretinal boundaries in a rapid fashion. RESULTS: 67,321 participants (134,642 eyes) in UK Biobank underwent OCT imaging of both eyes as part of the ocular module. 134,611 images were successfully processed with 31 images failing segmentation analysis due to corrupted OCT files or withdrawal of subject consent for UKBB study participation. Average time taken to call up an image from the database and complete segmentation analysis was approximately 120 seconds per data set per login, and analysis of the entire dataset was completed in approximately 28 days. CONCLUSIONS: We report an approach to the rapid, automated measurement of retinal thickness from nearly 140,000 OCT image sets from the UK Biobank. In the near future, these measurements will be publically available for utilization by researchers around the world, and thus for correlation with the wealth of other data collected in UK Biobank. The automated analysis approaches we describe may be of utility for future large population-based epidemiological studies, clinical trials, and screening programs that employ OCT imaging

    The ophthalmic branch of the Gutenberg Health Study: study design, cohort profile and self-reported diseases

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    This paper describes the study design, methodology, cohort profile and self-reported diseases in the ophthalmological branch of the Gutenberg Health Study (GHS).The GHS is an ongoing, prospective, interdisciplinary, single-center, population-based cohort study in Germany. The main goals of the ophthalmological section are to assess the prevalence and incidence of ocular diseases and to explore risk factors, genetic determinants and associations with systemic diseases and conditions. The eye examination at baseline included a medical history, self-reported eye diseases, visual acuity, refractive errors, intraocular pressure, visual field, pachymetry, keratometry, fundus photography and tear sampling. The 5-year follow-up visit additionally encompassed optical coherence tomography, anterior segment imaging and optical biometry. The general examination included anthropometry; blood pressure measurement; carotid artery ultrasound; electrocardiogram; echocardiography; spirometry; cognitive tests; questionnaires; assessment of mental conditions; and DNA, RNA, blood and urine sampling.Of 15,010 participants (aged 35-74 years at the time of inclusion), ocular data are available for 14,700 subjects (97.9%). The mean visual acuity (standard deviation), mean spherical equivalent, median decimal visual acuity, and mean intraocular pressure were 0.08 (0.17) logMar, -0.42 (2.43) diopters, 0.9 and 14.24 (2.79) mm Hg, respectively. The frequencies of self-reported strabismus, glaucoma, surgery for retinal detachment and retinal vascular occlusions were 2.7%, 2.3%, 0.2% and 0.4%, respectively.The GHS is the most extensive dataset of ophthalmic diseases and conditions and their risk factors in Germany and one of the largest cohorts worldwide. This dataset will provide new insight in the epidemiology of ophthalmic diseases and related medical specialties

    Peripheral Retinal Imaging Biomarkers for Alzheimer’s Disease: A Pilot Study

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    Purpose: To examine whether ultra-widefield (UWF) retinal imaging can identify biomarkers for Alzheimer's disease (AD) and its progression. Methods: Images were taken using a UWF scanning laser ophthalmoscope (Optos P200C AF) to determine phenotypic variations in 59 patients with AD and 48 healthy controls at baseline (BL). All living participants were invited for a follow-up (FU) after 2 years and imaged again (if still able to participate). All participants had blood taken for genotyping at BL. Images were graded for the prevalence of age-related macular degeneration-like pathologies and retinal vascular parameters. Comparison between AD patients and controls was made using the Student t test and the χ2 test. Results: Analysis at BL revealed a significantly higher prevalence of a hard drusen phenotype in the periphery of AD patients (14/55; 25.4%) compared to controls (2/48; 4.2%) [χ2 = 9.9, df = 4, p = 0.04]. A markedly increased drusen number was observed at the 2-year FU in patients with AD compared to controls. There was a significant increase in venular width gradient at BL (zone C: 8.425 × 10-3 ± 2.865 × 10-3 vs. 6.375 × 10-3 ± 1.532 × 10-3, p = 0.008; entire image: 8.235 × 10-3 ± 2.839 × 10-3 vs. 6.050 × 10-3 ± 1.414 × 10-3, p = 0.004) and a significant decrease in arterial fractal dimension in AD at BL (entire image: 1.250 ± 0.086 vs. 1.304 ± 0.089, p = 0.049) with a trend for both at FU. Conclusions: UWF retinal imaging revealed a significant association between AD and peripheral hard drusen formation and changes to the vasculature beyond the posterior pole, at BL and after clinical progression over 2 years, suggesting that monitoring pathological changes in the peripheral retina might become a valuable tool in AD monitoring

    The RADIOSTAR Project

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    © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).Radioactive nuclei are the key to understanding the circumstances of the birth of our Sun because meteoritic analysis has proven that many of them were present at that time. Their origin, however, has been so far elusive. The ERC-CoG-2016 RADIOSTAR project is dedicated to investigating the production of radioactive nuclei by nuclear reactions inside stars, their evolution in the Milky Way Galaxy, and their presence in molecular clouds. So far, we have discovered that: (i) radioactive nuclei produced by slow (107Pd and 182Hf) and rapid (129I and 247Cm) neutron captures originated from stellar sources —asymptotic giant branch (AGB) stars and compact binary mergers, respectively—within the galactic environment that predated the formation of the molecular cloud where the Sun was born; (ii) the time that elapsed from the birth of the cloud to the birth of the Sun was of the order of 107 years, and (iii) the abundances of the very short-lived nuclei 26Al, 36Cl, and 41Ca can be explained by massive star winds in single or binary systems, if these winds directly polluted the early Solar System. Our current and future work, as required to finalise the picture of the origin of radioactive nuclei in the Solar System, involves studying the possible origin of radioactive nuclei in the early Solar System from core-collapse supernovae, investigating the production of 107Pd in massive star winds, modelling the transport and mixing of radioactive nuclei in the galactic and molecular cloud medium, and calculating the galactic chemical evolution of 53Mn and 60Fe and of the p-process isotopes 92Nb and 146Sm.Peer reviewedFinal Published versio
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