We report an improved draft nucleotide sequence of the 2.3-gigabase genome of maize, an important crop plant and model for biological research. Over 32,000 genes were predicted, of which 99.8% were placed on reference chromosomes. Nearly 85% of the genome is composed of hundreds of families of transposable elements, dispersed nonuniformly across the genome. These were responsible for the capture and amplification of numerous gene fragments and affect the composition, sizes, and positions of centromeres. We also report on the correlation of methylation-poor regions with Mu transposon insertions and recombination, and copy number variants with insertions and/or deletions, as well as how uneven gene losses between duplicated regions were involved in returning an ancient allotetraploid to a genetically diploid state. These analyses inform and set the stage for further investigations to improve our understanding of the domestication and agricultural improvements of maize.

A recent mandate emphasizes severity of liver disease to determine priorities in allocating organs for liver transplantation and necessitates a disease severity index based on generalizable, verifiable, and easily obtained variables. The aim of the study was to examine the generalizability of a model previously created to estimate survival of patients undergoing the transjugular intrahepatic portosystemic shunt (TIPS) procedure in patient groups with a broader range of disease severity and etiology. The Model for End-Stage Liver Disease (MELD) consists of serum bilirubin and creatinine levels, International Normalized Ratio (INR) for prothrombin time, and etiology of liver disease. The model's validity was tested in 4 independent data sets, including (1) patients hospitalized for hepatic decompensation (referred to as "hospitalized" patients), (2) ambulatory patients with noncholestatic cirrhosis, (3) patients with primary biliary cirrhosis (PBC), and (4) unselected patients from the 1980s with cirrhosis (referred to as "historical" patients). In these patients, the model's ability to classify patients according to their risk of death was examined using the concordance (c)-statistic. The MELD scale performed well in predicting death within 3 months with a c-statistic of (1) 0.87 for hospitalized patients, (2) 0.80 for noncholestatic ambulatory patients, (3) 0.87 for PBC patients, and (4)

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BACKGROUND Under the current liver-transplantation policy, donor organs are offered to patients with the highest risk of death. METHODS Using data derived from all adult candidates for primary liver transplantation who were registered with the Organ Procurement and Transplantation Network in 2005 and 2006, we developed and validated a multivariable survival model to predict mortality at 90 days after registration. The predictor variable was the Model for End-Stage Liver Disease (MELD) score with and without the addition of the serum sodium concentration. The MELD score (on a scale of 6 to 40, with higher values indicating more severe disease) is calculated on the basis of the serum bilirubin and creatinine concentrations and the international normalized ratio for the prothrombin time. RESULTS In 2005, there were 6769 registrants, including 1781 who underwent liver transplantation and 422 who died within 90 days after registration on the waiting list. Both the MELD score and the serum sodium concentration were significantly associated with mortality (hazard ratio for death, 1.21 per MELD point and 1.05 per 1-unit decrease in the serum sodium concentration for values between 125 and 140 mmol per liter; P<0.001 for both variables). Furthermore, a significant interaction was found between the MELD score and the serum sodium concentration, indicating that the effect of the serum sodium concentration was greater in patients with a low MELD score. When applied to the data from 2006, when 477 patients died within 3 months after registration on the waiting list, the combination of the MELD score and the serum sodium concentration was considerably higher than the MELD score alone in 32 patients who died (7%). Thus, assignment of priority according to the MELD score combined with the serum sodium concentration might have resulted in transplantation and prevented death. CONCLUSIONS This population-wide study shows that the MELD score and the serum sodium concentration are important predictors of survival among candidates for liver transplantation.

The Model for End-stage Liver Disease (MELD) was initially created to predict survival in patients with complications of portal hypertension undergoing elective placement of transjugular intrahepatic portosystemic shunts. The MELD which uses only objective variables was validated subsequently as an accurate predictor of survival among different populations of patients with advanced liver disease. The major use of the MELD score has been in allocation of organs for liver transplantation. However, the MELD score has also been shown to predict survival in patients with cirrhosis who have infections, variceal bleeding, as well as in patients with fulminant hepatic failure and alcoholic hepatitis. MELD may be used in selection of patients for surgery other than liver transplantation and in determining optimal treatment for patients with hepatocellular carcinoma who are not candidates for liver trans- becoming the standard by which priorities in donor liver allocation were determined. Since the score was first derived in a relatively small number of patients undergoing the transjugular intrahepatic portosystemic shunts (TIPS) procedure, it has been validated in many different populations of patients with liver disease. Within a relatively short period of time, MELD became a common metric by which the severity of liver disease could be accurately described.In this paper, we review the initial development and validation of the MELD score, its application in organ allocation and management of patients with a variety of liver conditions, its strengths and limitation, and current and future efforts to refine and improve it further. Creation and Validation of MELDMELD was initially created to predict survival following elective placement of TIPS. 1 The model was subsequently validated as a predictor of survival in several cohorts of patients with varying levels of liver disease severity (e.g., hospitalized and ambulatory patients), as well as patients of geographically and temporally diverse origin. 2 The survival model was initially termed the "Mayo End-Stage Liver Disease" or "MELD" model to acknowledge the affiliation of the investigators who created the model. During discussions leading to the establishment of MELD as the basis for prioritization of organs for liver transplantation, 3,4 we changed the name to "Model for End-Stage Liver Disease" which maintained the acronym "MELD", but removed the association with a particular institution, a process that was thought would lead to wider acceptance of the model. MELD incorporates 3 widely available laboratory variables including the international normalized ratio (INR), serum creatinine, and serum bilirubin. The original mathematical formula for MELD is: MELD ϭ 9.57 ϫ log e (creatinine) ϩ 3.78 ϫ Log e (total bilirubin) ϩ 11.2 ϫ Log e (INR) ϩ 6.43.The score can be calculated on handheld computing devices, and is available at www.mayoclinic.org/gi-rst/ mayomodel5.html. When the model was initially created the etiology of cirrhosis was also included. In the TIPS