Single-nucleotide polymorphism associations with preterm delivery: a case-control replication study and meta-analysis

BackgroundThe aim of this study was to replicate single-nucleotide polymorphism (SNP) associations with preterm birth (PTB; birth at MethodsSpontaneous PTB cases and controls were selected from an existing cohort. Candidate SNPs were taken from an existing genotype panel. A systematic review was conducted for each SNP in the panel to determine suitability as a PTB candidate. Those with significant associations previously reported in Caucasians were selected for replication. Candidate SNPs were already genotyped in cases and controls and clinical data were accessed from state perinatal and cerebral palsy databases. Association analysis was conducted between each SNP and PTB, and meta-analysis was conducted if there were ≥ 3 studies in the literature. Maternal and fetal SNPs were considered as separate candidates.ResultsA cohort of 170 cases and 583 controls was formed. Eight SNPs from the original panel of genotyped SNPs were selected as PTB candidates and for replication on the basis of systematic literature review results. In our cohort, fetal factor V Leiden (FVL) was significantly associated with PTB (odds ratio (OR): 2.6, 95% confidence interval (CI): 1.31-5.17), and meta-analysis confirmed this association (OR: 2.71, 95% CI: 1.15-6.4).ConclusionReplication and meta-analysis support an increased risk of PTB in Caucasians with the fetal FVL mutation.Michael E. O’Callaghan, Alastair H. MacLennan, Gai L. McMichael, Eric A. Haan and Gustaaf A. Dekke

A double-blind, randomized, placebo-controlled trial of prostaglandin E 1 in liver transplantation

A double-blind placebo-controlled trial of intravenous prostaglandin PGE 1 (40 Μg/h) was conducted in adult orthotopic liver transplant recipients. Infusion was started intraoperatively and continued for up to 21 days. Patients were followed up for 180 days postoperatively. Among 172 patients eligible for treatment in the study, 160 could be evaluated (78 PGE 1 ; 82 placebo). Patient and graft survival were similar (PGE 1 : 16 deaths, 9 retransplantations [7 survivors]; controls: 15 deaths, 6 retransplantations [3 survivors]). In patients with surviving grafts, however, PGE 1 administration resulted in a 23% shorter mean duration of hospitalization following transplantation (PGE 1 : 24.4 days; controls: 31.8 days; P = .02) and 40% shorter length of time postoperatively in the intensive care unit (PGE 1 : 8.2 days; controls 13.7 days; P = .05). Reduced needs for renal support ( P = .03) or surgical intervention other than retransplantation ( P = .02) were also noted with PGE 1 use. Further, PGE 1 administration resulted in a trend toward improved survival rates in patients with mild renal impairment (preoperative serum creatinine 1.5 mg percent or greater; P = .08). Neither the incidence of acute cellular rejection nor of primary nonfunction was significantly different in the two groups. Phlebitis was the only complication that was more common during PGE 1 administration, (PGE 1 : 9; controls: 4). These results suggest that PGE 1 use in hepatic allograft recipients reduces morbidity and may result in sizable cost reductions. (H EPATOLOGY 1995;21:366–372.)Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/38409/1/1840210216_ftp.pd

Global report on preterm birth and stillbirth (2 of 7): discovery science

<p>Abstract</p> <p>Background</p> <p>Normal and abnormal processes of pregnancy and childbirth are poorly understood. This second article in a global report explains what is known about the etiologies of preterm births and stillbirths and identifies critical gaps in knowledge. Two important concepts emerge: the continuum of pregnancy, beginning at implantation and ending with uterine involution following birth; and the multifactorial etiologies of preterm birth and stillbirth. Improved tools and data will enable discovery scientists to identify causal pathways and cost-effective interventions.</p> <p>Pregnancy and parturition continuum</p> <p>The biological process of pregnancy and childbirth begins with implantation and, after birth, ends with the return of the uterus to its previous state. The majority of pregnancy is characterized by rapid uterine and fetal growth without contractions. Yet most research has addressed only uterine stimulation (labor) that accounts for <0.5% of pregnancy.</p> <p>Etiologies</p> <p>The etiologies of preterm birth and stillbirth differ by gestational age, genetics, and environmental factors. Approximately 30% of all preterm births are indicated for either maternal or fetal complications, such as maternal illness or fetal growth restriction. Commonly recognized pathways leading to preterm birth occur most often during the gestational ages indicated: (1) inflammation caused by infection (22-32 weeks); (2) decidual hemorrhage caused by uteroplacental thrombosis (early or late preterm birth); (3) stress (32-36 weeks); and (4) uterine overdistention, often caused by multiple fetuses (32-36 weeks). Other contributors include cervical insufficiency, smoking, and systemic infections. Many stillbirths have similar causes and mechanisms. About two-thirds of late fetal deaths occur during the antepartum period; the other third occur during childbirth. Intrapartum asphyxia is a leading cause of stillbirths in low- and middle-income countries.</p> <p>Recommendations</p> <p>Utilizing new systems biology tools, opportunities now exist for researchers to investigate various pathways important to normal and abnormal pregnancies. Improved access to quality data and biological specimens are critical to advancing discovery science. Phenotypes, standardized definitions, and uniform criteria for assessing preterm birth and stillbirth outcomes are other immediate research needs.</p> <p>Conclusion</p> <p>Preterm birth and stillbirth have multifactorial etiologies. More resources must be directed toward accelerating our understanding of these complex processes, and identifying upstream and cost-effective solutions that will improve these pregnancy outcomes.</p

Stability, consistency, and heritability of electrodermal response lability in middle-aged male twins

Abstract We examined individual differences in nonspecific electrodermal response (EDR) lability in terms of retest stability, cross-situational consistency, and heritability in a sample of 345 adult monozygotic and dizygotic twin pairs. We also examined the phenotypic and genetic relationships between EDR lability and speed of habituation of the specific EDR to a nonsignal stimulus. Individual variation in EDR lability showed substantial retest stability and cross-situational consistency and also predicted resistance to specific EDR habituation. Structural equation modeling showed that the covariation among EDR lability measures and resistance to specific EDR habituation operated through a single latent phenotype, which was influenced in approximately equal measure by genetic and unique environmental factors. We discuss these findings in terms of an information processing account of individual differences in phasic EDR activation. Descriptors: Individual differences, Electrodermal response lability, Temporal stability, Cross-situational consistency, Behavioral genetics, Twin study Electrodermal response (EDR) lability is most commonly defined by individual differences in the rate of emission of nonspecific (spontaneous) EDRs under resting conditions. Because resting assessments of nonspecific EDR activity are known to be stable on retest, EDR lability is often regarded as a psychophysiological trait The question of the cross-situational consistency of nonspecific EDR lability has received relatively little attention. An influential early study b

Towards a Standardization for Simulation Scenario Development in Aviation - Panel Discussion

Aviation industry is characterized by its broad utilization of modeling and simulation starting from concept demonstration to operator training. Scenario development is an important aspect of any simulation study, however, the community is still lacking of a common understanding and standardized practices. This leads to degraded interoperability and shareability. The American Institute of Aeronautics and Astronautics (AIAA) Modeling and Simulation Technical Committee (MSTC) is recently trying to create a synergy towards development of a standard scenario definition language for aviation by conducting sessions and panel discussions in conferences and launching a working group. This paper presents the recap of the panel discussion that has been carried out as a part of the invited session “Aviation Simulation Scenario Development” in AIAA Modeling and Simulation Technologies Conference of Scitech 2017