BACKGROUNDDespite evidence that genetic factors contribute to the duration of gestation and the risk of preterm birth, robust associations with genetic variants have not been identified. We used large data sets that included the gestational duration to determine possible genetic associations. METHODSWe performed a genomewide association study in a discovery set of samples obtained from 43,568 women of European ancestry using gestational duration as a continuous trait and term or preterm (<37 weeks) birth as a dichotomous outcome. We used samples from three Nordic data sets (involving a total of 8643 women) to test for replication of genomic loci that had significant genomewide association (P<5.0×10 −8 ) or an association with suggestive significance (P<1.0×10 −6 ) in the discovery set. RESULTSIn the discovery and replication data sets, four loci (EBF1, EEFSEC, AGTR2, and WNT4) were significantly associated with gestational duration. Functional analysis showed that an implicated variant in WNT4 alters the binding of the estrogen receptor. The association between variants in ADCY5 and RAP2C and gestational duration had suggestive significance in the discovery set and significant evidence of association in the replication sets; these variants also showed genomewide significance in a joint analysis. Common variants in EBF1, EEFSEC, and AGTR2 showed association with preterm birth with genomewide significance. An analysis of mother-infant dyads suggested that these variants act at the level of the maternal genome. CONCLUSIONSIn this genomewide association study, we found that variants at the EBF1, EEFSEC, AGTR2, WNT4, ADCY5, and RAP2C loci were associated with gestational duration and

The effect of heart rate on cardiac output and associated rate induced hemodynamic changes in dogs with chronic heart block is presented and discussed. At heart rates below 60/min., the stroke volume was maximum and relatively constant, and the cardiac output was largely rate-dependent. These relationships did not exist at ventricular rates above 60/min. Cinefluorographic evidence of decreased diastolic ventricular filling with increasing ventricular rates is presented. At very slow and very fast ventricular rates, the cardiac output decreased despite an increase in right atrial and right ventricular end-diastolic pressure. At slow rates the decreased output was due to rate alone, while at rapid rates it was attributed to the decreased diastolic filling period and resistance to ventricular distention, resulting in decreased diastolic filling.

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The IRIS catheter allows direct in vivo visualization of the interatrial septum to guide transseptal puncture of previous punctures.