30 research outputs found
A Population Based Ultra-Widefield Digital Image Grading Study for AMD-like Lesions at the Peripheral Retina
Peripheral Retinal Imaging Biomarkers for Alzheimer’s Disease: A Pilot Study
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
Neuronal and astrocyte dysfunction diverges from embryonic fibroblasts in the Ndufs4fky/fky mouse
Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease
We identified rare coding variants associated with Alzheimer’s disease (AD) in a 3-stage case-control study of 85,133 subjects. In stage 1, 34,174 samples were genotyped using a whole-exome microarray. In stage 2, we tested associated variants (P<1×10-4) in 35,962 independent samples using de novo genotyping and imputed genotypes. In stage 3, an additional 14,997 samples were used to test the most significant stage 2 associations (P<5×10-8) using imputed genotypes. We observed 3 novel genome-wide significant (GWS) AD associated non-synonymous variants; a protective variant in PLCG2 (rs72824905/p.P522R, P=5.38×10-10, OR=0.68, MAFcases=0.0059, MAFcontrols=0.0093), a risk variant in ABI3 (rs616338/p.S209F, P=4.56×10-10, OR=1.43, MAFcases=0.011, MAFcontrols=0.008), and a novel GWS variant in TREM2 (rs143332484/p.R62H, P=1.55×10-14, OR=1.67, MAFcases=0.0143, MAFcontrols=0.0089), a known AD susceptibility gene. These protein-coding changes are in genes highly expressed in microglia and highlight an immune-related protein-protein interaction network enriched for previously identified AD risk genes. These genetic findings provide additional evidence that the microglia-mediated innate immune response contributes directly to AD development
Finishing the euchromatic sequence of the human genome
The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead
The Fiscal Anatomy of a Regulatory Polity: Tax Policy and Multilevel Governance in the EU
Skills development strategy: together we are getting the skills development show on the road
Paper presented at the South African Transport Conference 17 - 20 July 2000 "Action in transport for the new millennium", CSIR International Convention Centre, Pretoria, South Africa. ABSTRACT: The Skills Development Strategy of the Minister of Labour is intended to provide a framework and set of strategic objectives within which industry and government can massively increase their commitment to
uplifting their people - not just in general but specifically in order to achieve their own strategic priorities and targets.
Whilst the long term incentive is to ensure that people are able to design and implement strategies for economic and employment growth and social development - the short term incentive is money! The Skills
Development Levies Act introduces a Skills Development Levy which collects a small percentage (0,5% in the first year, and 1% in the years thereafter) of payroll from all employers, and then makes these funds
available as grants to those employers that train. Those that choose not to claim will end up subsidizing those that do - and hence everyone will be contributing towards the upliftment of our people. Some 20% of the funds collected will be used to support the training of the unemployed and vulnerable members of our society.
Whilst the money is to be collected by the South African Revenue Services, 80% of it will be managed and disbursed by industry contolled bodies (on which the relevant government department may also play a key
role) to be known as Sector Education and Training Authorities or SETAs. These SETAs are charged, under the legislation, to keep a close relationship with the employers in their sector and ensure that future trends
and challenges are anticipated in respect of skills.
The transport sector is no different. The Transport Education and Training Sector or TETA, like other SETAs, has been established and now carries the mandate to carry forward the skills development revolution in the
sector. It must scan the industry - and all the sub-industries - to determine priorities and targets aligned to national strategic initiatives of government and induced by the market or technology, it must disburse the
grant to firms that train, and it must ensure that the training that does take place is of an industry-approved
(and indeed national) standard. It must also ensure that groups, such as the taxi's and other smaller players in the industry are not neglected. It also needs to replenish the industry's skills pool by entering young people and others in learnerships.
The Skills Revolution has begun - but needs industry's support to be fully realised.This paper was transferred from the original CD ROM created for this conference. The material on the CD ROM was published using Adobe Acrobat technology. The original CD ROM was produced by Document Transformation Technologies Postal Address: PO Box 560 Irene 0062 South Africa. Tel.: +27 12 667 2074 Fax: +27 12 667 2766 E-mail: [email protected] URL: http://www.doctech.co.z
High Baseline Prevalence of Depression & Hba1C >= 6.5% in Acute Coronary Syndrome: the Advent Study
Comparing test‐specific distress of susceptibility versus deterministic genetic testing for Alzheimer’s disease
Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/152479/1/alzjjalz200804007.pd