The 1000 Genomes Project set out to provide a comprehensive description of common human genetic variation by applying whole-genome sequencing to a diverse set of individuals from multiple populations. Here we report completion of the project, having reconstructed the genomes of 2,504 individuals from 26 populations using a combination of low-coverage whole-genome sequencing, deep exome sequencing, and dense microarray genotyping. We characterized a broad spectrum of genetic variation, in total over 88 million variants (84.7 million single nucleotide polymorphisms (SNPs), 3.6 million short insertions/deletions (indels), and 60,000 structural variants), all phased onto high-quality haplotypes. This resource includes >99% of SNP variants with a frequency of >1% for a variety of ancestries. We describe the distribution of genetic variation across the global sample, and discuss the implications for common disease studies.

https://cdr.lib.unc.edu/downloads/v692t8920

A global reference for human genetic variation.

Objective To determine the effects of antiplatelet therapy among patients at high risk of occlusive vascular events. Design Collaborative meta-analyses (systematic overviews). Inclusion criteria Randomised trials of an antiplatelet regimen versus control or of one antiplatelet regimen versus another in high risk patients (with acute or previous vascular disease or some other predisposing condition) from which results were available before September 1997. Trials had to use a method of randomisation that precluded prior knowledge of the next treatment to be allocated and comparisons had to be unconfounded-that is, have study groups that differed only in terms of antiplatelet regimen. Studies reviewed 287 studies involving 135 000 patients in comparisons of antiplatelet therapy versus control and 77 000 in comparisons of different antiplatelet regimens. Main outcome measure "Serious vascular event": non-fatal myocardial infarction, non-fatal stroke, or vascular death. Results Overall, among these High risk patients, allocation to antiplatelet therapy reduced the combined outcome of any serious vascular event by about one quarter; non-fatal myocardial infarction was reduced by one third, non-fatal stroke by one quarter, and vascular mortality by one sixth (with no apparent adverse effect on other deaths). Absolute reductions in the risk of having a serious vascular event were 36 (SE 5) per 1000 treated for two years among patients with previous myocardial infarction; 38 (5) per 1000 patients treated for one month among patients with acute myocardial infarction; 36 (6) per 1000 treated for two years among those with previous stroke or transient ischaemic attack; 9 (3) per 1000 treated for three weeks among those with acute stroke; and 22 (3) per 1000 treated for two years among other high risk patients (with separately significant results for those with stable angina (P=0.0005), peripheral arterial disease (P=0.004), and atrial fibrillation (P=0.01)). In each of these high risk categories, the absolute benefits substantially outweighed the absolute risks of major extracranial bleeding. Aspirin was the most widely studied antiplatelet drug, with doses of 75-150 mg daily at least as effective as higher daily doses. The effects of doses lower than 75 mg daily were less certain. Clopidogrel reduced serious vascular events by 10% (4%) compared with aspirin, which was similar to the 12% (7%) reduction observed with its analogue ticlopidine. Addition of dipyridamole to aspirin produced no significant further reduction in vascular events compared with aspirin alone. Among patients at high risk of immediate coronary occlusion, short term addition of an intravenous glycoprotein IIb/IIIa antagonist to aspirin prevented a further 20 (4) vascular events per 1000 (P <0.0001) but caused 23 major (but rarely fatal) extracranial bleeds per 1000. Conclusions Aspirin (or another oral antiplatelet drug) is protective in most types of patient at increased risk of occlusive vascular events, including those with an acute myocardial infarction or ischaemic stroke, unstable or stable angina, previous myocardial infarction, stroke or cerebral ischaemia, peripheral arterial disease, or atrial fibrillation, Low dose aspirin (75-150 mg daily) is an effective antiplatelet regimen for long term use, but in acute settings an initial loading dose of at least 150 mg aspirin may be required. Adding a second antiplatelet drug to aspirin may produce additional benefits in some clinical circumstances, but more research into this strategy is needed.

/pdf/collaborative-meta-analysis-of-randomised-trials-of-8dyu3duelv.pdf

Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients

Background Retinal ischemia induces intraocular neovascularization, which often leads to glaucoma, vitreous hemorrhage, and retinal detachment, presumably by stimulating the release of angiogenic molecules. Vascular endothelial growth factor (VEGF) is an endothelial-cell-specific angiogenic factor whose production is increased by hypoxia. Methods We measured the concentration of VEGF in 210 specimens of ocular fluid obtained from 164 patients undergoing intraocular surgery, using both radioimmunoassays and radioreceptor assays. Vitreous proliferative potential was measured with in vitro assays of the growth of retinal endothelial cells and with VEGF-neutralizing antibody. Results VEGF was detected in 69 of 136 ocular-fluid samples from patients with diabetic retinopathy, 29 of 38 samples from patients with neovascularization of the iris, and 3 of 4 samples from patients with ischemic occlusion of the central retinal vein, as compared with 2 of 31 samples from patients with no neovascular disorders (P<0.00...

https://www.nejm.org/doi/pdf/10.1056/NEJM199412013312203

Vascular Endothelial Growth Factor in Ocular Fluid of Patients with Diabetic Retinopathy and Other Retinal Disorders

A global reference for human genetic variation

Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials.

Serous macular detachment in Waldenström macroglobulinemia: a report of four cases.

• Patients with sickle cell disease can have a distinct retinopathy in which the posterior pole shows abnormalities, including perifoveolar vascular abnormalities. The foveal avascular zone (FAZ) was examined using fluorescein angiography in patients with sickle cell disease and in healthy normal controls. The longest FAZ diameters of 38 patients (51 eyes) with sickle cell disease were compared with those of the 48 patients (60 eyes) in the control group. The average of the longest FAZ diameter in the patients with sickle cell disease was 1.00 mm compared with 0.61 mm for the controls. This difference was statistically significant ( P

Foveal Avascular Zone Diameter and Sickle Cell Disease

OBJECTIVE: The purpose of this study was to determine the effectiveness of laser photocoagulation in eyes with threshold retinopathy of prematurity (ROP), defined as stage 3+, zone 2, with 5 or more contiguous or 8 cumulative clock hours of extraretinal fibrovascular proliferation METHODS: Indirect ophthalmoscopic retinal examinations were performed on 18 premature infants born between 1991 and 1993 to identify those eyes with threshold ROP Diode laser was used to treat 31 eyes within 48 hours of diagnosis Each patient was followed post treatment at weekly intervals until regression was starting to occur Subsequent follow-up visits were tailored to each patient RESULTS: During the 41 to 60 month follow-up (average 49 months, median 46 months), 27 of 31 lasered eyes (87%) demonstrated regression of the extraretinal neovascularization, and 26 (84%) had functional vision This includes two Stage 4B eyes that were reattached with scleral buckles Twenty-two eyes (71%) were myopic and four (13%) progressed to stage 5 retinal detachment that could not be repaired No cataracts occurred in this group of patients CONCLUSIONS: Although a potentially blinding disorder, threshold ROP is, in many cases, treatable with laser photocoagulation, which may be easier to administer than cryotherapy Follow-up of patients treated with diode laser demonstrates that functional vision is attainable

Diode laser photocoagulation for retinopathy of prematurity.

Malignant transformation of congenital hypertrophy of the retinal pigment epithelium.

Purpose:The purpose of this study was to use a cross-sectional prevalence-based health care economic survey to ascertain the annual, incremental, societal ophthalmic costs associated with neovascular age-related macular degeneration.Methods:Consecutive patients (n = 200) with neovascular age-related

Gary C. Brown

Papers

Serous macular detachment in Waldenström macroglobulinemia: a report of four cases.

Foveal Avascular Zone Diameter and Sickle Cell Disease

Diode laser photocoagulation for retinopathy of prematurity.

Malignant transformation of congenital hypertrophy of the retinal pigment epithelium.

Societal costs associated with neovascular age-related macular degeneration in the united states.