166 research outputs found
Replication of TCF4 through Association and Linkage Studies in Late-Onset Fuchs Endothelial Corneal Dystrophy
Fuchs endothelial corneal dystrophy (FECD) is a common, late-onset disorder of
the corneal endothelium. Although progress has been made in understanding the
genetic basis of FECD by studying large families in which the phenotype is
transmitted in an autosomal dominant fashion, a recently reported genome-wide
association study identified common alleles at a locus on chromosome 18 near
TCF4 which confer susceptibility to FECD. Here, we report
the findings of our independent validation study for TCF4 using
the largest FECD dataset to date (450 FECD cases and 340 normal controls).
Logistic regression with sex as a covariate was performed for three genetic
models: dominant (DOM), additive (ADD), and recessive (REC). We found
significant association with rs613872, the target marker reported by Baratz
et al.(2010), for all three genetic models (DOM:
P = 9.33×10−35;
ADD:
P = 7.48×10−30;
REC:
P = 5.27×10−6).
To strengthen the association study, we also conducted a genome-wide linkage
scan on 64 multiplex families, composed primarily of affected sibling pairs
(ASPs), using both parametric and non-parametric two-point and multipoint
analyses. The most significant linkage region localizes to chromosome 18 from
69.94cM to 85.29cM, with a peak multipoint
HLOD = 2.5 at rs1145315 (75.58cM) under the DOM
model, mapping 1.5 Mb proximal to rs613872. In summary, our study presents
evidence to support the role of the intronic TCF4 single
nucleotide polymorphism rs613872 in late-onset FECD through both association and
linkage studies
The James Webb Space Telescope Mission
Twenty-six years ago a small committee report, building on earlier studies,
expounded a compelling and poetic vision for the future of astronomy, calling
for an infrared-optimized space telescope with an aperture of at least .
With the support of their governments in the US, Europe, and Canada, 20,000
people realized that vision as the James Webb Space Telescope. A
generation of astronomers will celebrate their accomplishments for the life of
the mission, potentially as long as 20 years, and beyond. This report and the
scientific discoveries that follow are extended thank-you notes to the 20,000
team members. The telescope is working perfectly, with much better image
quality than expected. In this and accompanying papers, we give a brief
history, describe the observatory, outline its objectives and current observing
program, and discuss the inventions and people who made it possible. We cite
detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space
Telescope Overview, 29 pages, 4 figure
Optimisation of Perioperative Cardiovascular Management to Improve Surgical Outcome II (OPTIMISE II) trial: study protocol for a multicentre international trial of cardiac output-guided fluid therapy with low-dose inotrope infusion compared with usual care in patients undergoing major elective gastrointestinal surgery.
INTRODUCTION: Postoperative morbidity and mortality in older patients with comorbidities undergoing gastrointestinal surgery are a major burden on healthcare systems. Infections after surgery are common in such patients, prolonging hospitalisation and reducing postoperative short-term and long-term survival. Optimal management of perioperative intravenous fluids and inotropic drugs may reduce infection rates and improve outcomes from surgery. Previous small trials of cardiac-output-guided haemodynamic therapy algorithms suggested a modest reduction in postoperative morbidity. A large definitive trial is needed to confirm or refute this and inform widespread clinical practice. METHODS: The Optimisation of Perioperative Cardiovascular Management to Improve Surgical Outcome II (OPTIMISE II) trial is a multicentre, international, parallel group, open, randomised controlled trial. 2502 high-risk patients undergoing major elective gastrointestinal surgery will be randomly allocated in a 1:1 ratio using minimisation to minimally invasive cardiac output monitoring to guide protocolised administration of intravenous fluid combined with low-dose inotrope infusion, or usual care. The trial intervention will be carried out during and for 4 hours after surgery. The primary outcome is postoperative infection of Clavien-Dindo grade II or higher within 30 days of randomisation. Participants and those delivering the intervention will not be blinded to treatment allocation; however, outcome assessors will be blinded when feasible. Participant recruitment started in January 2017 and is scheduled to last 3 years, within 50 hospitals worldwide. ETHICS/DISSEMINATION: The OPTIMISE II trial has been approved by the UK National Research Ethics Service and has been approved by responsible ethics committees in all participating countries. The findings will be disseminated through publication in a widely accessible peer-reviewed scientific journal. TRIAL REGISTRATION NUMBER: ISRCTN39653756.The OPTIMISE II trial is supported by Edwards Lifesciences (Irvine, CA) and the UK National Institute for Health Research through RMP’s NIHR Professorship
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