Model for end-stage liver disease (MELD) exception guidelines: Results and recommendations from the MELD exception study group and conference (MESSAGE) for the approval of patients who need liver transplantation with diseases not considered by the standard MELD formula

No abstract.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/55914/1/20979_ftp.pd

Continuing to deliver: the evidence base for pre-implantation genetic screening

International audienc

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 $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ 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

Distinct genetic architectures for syndromic and nonsyndromic congenital heart defects identified by exome sequencing.

Congenital heart defects (CHDs) have a neonatal incidence of 0.8-1% (refs. 1,2). Despite abundant examples of monogenic CHD in humans and mice, CHD has a low absolute sibling recurrence risk (∼2.7%), suggesting a considerable role for de novo mutations (DNMs) and/or incomplete penetrance. De novo protein-truncating variants (PTVs) have been shown to be enriched among the 10% of 'syndromic' patients with extra-cardiac manifestations. We exome sequenced 1,891 probands, including both syndromic CHD (S-CHD, n = 610) and nonsyndromic CHD (NS-CHD, n = 1,281). In S-CHD, we confirmed a significant enrichment of de novo PTVs but not inherited PTVs in known CHD-associated genes, consistent with recent findings. Conversely, in NS-CHD we observed significant enrichment of PTVs inherited from unaffected parents in CHD-associated genes. We identified three genome-wide significant S-CHD disorders caused by DNMs in CHD4, CDK13 and PRKD1. Our study finds evidence for distinct genetic architectures underlying the low sibling recurrence risk in S-CHD and NS-CHD

Transplantation of livers from HBc Ab positive donors into HBc Ab negative recipients: a strategy and preliminary results

Here we describe a strategy for using livers from hepatitis B core antibody (anti-HBc) positive donors in anti-HBc negative recipients and report our preliminary results. Adult anti-HBc negative recipients were immunized against hepatitis B virus (HBV) prior to transplantation. Liver biopsies from anti-HBc positive, HBs Ag negative donors were performed at the time of procurement to rule out acute hepatitis or chronic liver disease. Donor serum and liver samples were collected for HBV DNA analysis by PCR. Recipients were given HBIG (10 000 units, i.v.) during the anhepatic phase of transplantation. Patients were treated with lamivudine (150 mg) beginning on postoperative day (POD) 1. If HBV DNA was not detected in either donor liver or serum by PCR, recipient antiviral therapy was stopped. If donor liver and serum were positive for HBV DNA by PCR, the recipient was maintained on combination lamivudine and HBIG therapy. If HBV DNA was detected in donor liver but not in donor serum, the patient was managed on lamivudine therapy alone. Between February 1999 and June 2000, six anti-HBc negative recipients received liver transplants from anti-HBc positive donors. PCR analysis of serum from the six donors was negative for HBV DNA in each, while donor liver PCR analysis was positive in five of six for HBV DNA. Accordingly, all patients were given HBIG in the anhepatic phase of transplantation and five of six were maintained on daily lamivudine therapy. Follow-up periods have ranged from 2 to 18 months. There has been no emergence of de novo hepatitis B. Serial serum HBs Ag and HBV DNA assays have all proven negative. Moreover, while on lamivudine therapy, 2 patients now have undetectable HBV DNA in hepatic allograft biopsies by PCR analysis. Our strategy for using livers from anti-HBc donors has yielded promising initial results. De novo hepatitis B has not occurred and our data suggest residual hepatitis B virus may be eradicated in recipients maintained on lamivudine therapy