Aims Plasma volume (PV) expansion hallmarks worsening chronic heart failure (CHF) but no non‐invasive means of quantifying volume status exists. Because weight and haematocrit are related to PV, they can be used to calculate relative PV status (PVS). We tested the validity and prognostic utility of calculated PVS in CHF patients. Methods and results First, we evaluated the agreement between calculated actual PV (aPV) and aPV levels measured using 125Iodine‐human serum albumin. Second, we derived PVS as: [(calculated aPV – ideal PV)/ideal PV] × 100%. Third, we assessed the prognostic implications of PVS in 5002 patients from the Valsartan in Heart Failure Trial (Val‐HeFT), and validated this in another 246 routine CHF outpatients. On analysis, calculated and measured aPV values correlated significantly in 119 normal subjects and 30 CHF patients. In the Val‐HeFT cohort, mean (+SD) PVS was –9 ± 8% and related to volume biomarkers such as brain natriuretic peptide (BNP). Over 2 years, 977 (20%) patients died. Plasma volume status was associated with death and first morbid events in a ‘J‐shaped’ fashion with the highest risk seen with a PVS > –4%. Stratification into PVS quartiles confirmed that a PVS > –4% was associated with increased mortality (unadjusted hazard ratio 1.65, 95% confidence interval 1.44–1.88, χ2 = 54, P < 0.001) even after adjusting for 22 variables, including brain natriuretic peptide. These results were mirrored in the validation cohort. Conclusions Relative PVS calculated from simple clinical indices reflects the degree to which patients have deviated from their ideal PV and independently relates to outcomes. The utility of PVS‐driven CHF management needs further evaluation.

During October–December 2016, the number of norovirus outbreaks in China increased sharply from the same period during the previous 4 years. We identified a recombinant norovirus strain, GII.P16-GII.2, as the cause of 44 (79%) of the 56 outbreaks, signaling that this strain could replace the predominant GII.4 viruses.

A dozen genes/regions have been confirmed as genetic risk factors for oral clefts in human association and linkage studies, and animal models argue even more genes may be involved. Genomic sequencing studies should identify specific causal variants and may reveal additional genes as influencing risk to oral clefts, which have a complex and heterogeneous etiology. We conducted a whole exome sequencing (WES) study to search for potentially causal variants using affected relatives drawn from multiplex cleft families. Two or three affected second, third, and higher degree relatives from 55 multiplex families were sequenced. We examined rare single nucleotide variants (SNVs) shared by affected relatives in 348 recognized candidate genes. Exact probabilities that affected relatives would share these rare variants were calculated, given pedigree structures, and corrected for the number of variants tested. Five novel and potentially damaging SNVs shared by affected distant relatives were found and confirmed by Sanger sequencing. One damaging SNV in CDH1, shared by three affected second cousins from a single family, attained statistical significance (P = 0.02 after correcting for multiple tests). Family-based designs such as the one used in this WES study offer important advantages for identifying genes likely to be causing complex and heterogeneous disorders.

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