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We conducted this phase I, open-label safety and feasibility trial of autologous cord blood (CB) stem cell (CBSC) therapy via a novel blood cardioplegia-based intracoronary infusion technique during the Norwood procedure in neonates with an antenatal diagnosis of hypoplastic left heart syndrome (HLHS). CBSC therapy may support early cardiac remodeling with enhancement of right ventricle (RV) function during the critical interstage period. Clinical grade CB mononucleated cells (CBMNCs) were processed to NetCord-FACT International Standards. To maximize yield, CBSCs were not isolated from CBMNCs. CBMNCs were stored at 4 °C (no cryopreservation) for use within 3 days and delivered after each cardioplegia dose (4 × 15 mL). Of 16 patients with antenatal diagnosis, 13 were recruited; of these 13 patients, 3 were not treated due to placental abruption (n = 1) or conditions delaying the Norwood for >4 days (n = 2) and 10 received 644.9 ± 134 × 106 CBMNCs, representing 1.5 ± 1.1 × 106 (CD34+) CBSCs. Interstage mortality was 30% (n = 3; on days 7, 25, and 62). None of the 36 serious adverse events (53% linked to 3 deaths) were related to CBMNC therapy. Cardiac magnetic resonance imaging before stage 2 (n = 5) found an RV mass index comparable to that in an exact-matched historical cohort (n = 22), with a mean RV ejection fraction of 66.2 ± 4.5% and mean indexed stroke volume of 47.4 ± 6.2 mL/m2 versus 53.5 ± 11.6% and 37.2 ± 10.3 mL/m2, respectively. All 7 survivors completed stage 2 and are alive with normal RV function (6 with ≤mild and 1 with moderate tricuspid regurgitation). This trial demonstrated that autologous CBMNCs delivered in large numbers without prior cryopreservation via a novel intracoronary infusion technique at cardioplegic arrest during Norwood palliation on days 2 to 3 of life is feasible and safe. [ABSTRACT FROM AUTHOR]

Background One potential approach for advancing univentricular heart surgical palliation outcomes is by stem cell therapy to augment right ventricular function and muscle mass. Whether the stem cell–inclusive cord blood mononuclear cells (CBMNCs) are safe to perfuse into the coronary vasculature during neonatal cardiopulmonary bypass (CPB) is unknown. We evaluated the acute safety, functional effects, and fate of human CBMNCs in a novel model of coronary vasculature delivery in a lamb model of infant CPB. Methods Neonatal lambs were randomized in blinded fashion to receive control (n = 5) or human CD45 + CBMNCs (8 × 10 6 cells/kg body weight, n = 7) treatments during CPB. Aortic cross-clamp time was 40 minutes, with maintenance blood cardioplegia delivered every 10 minutes. Pressure-volume indices were used to measure left ventricular function before CPB and 60 minutes after CPB. CBMNCs were assessed by flow cytometry and immunohistochemistry. Results CBMNC-treated lambs were hemodynamically stable after CPB, with a decline in left ventricular pressure-volume indices similar to controls. The coronary vasculature was patent on microscopy, without evidence of cell aggregates or clots. Human CD45 + cells were distributed in high abundance within all cardiac regions, predominantly the right atrium and ventricles, and trafficked beyond endothelial cell layers and between myocytes. CD45 + cells localized at low incidence in the spleen, liver, lungs, and kidneys, but rarely remained in the circulation (<0.1% of infused cells). Conclusions Coronary delivery of human CBMNCs during blood-cardioplegic arrest in a lamb model of CPB results in highly abundant myocardial distribution of cells without acute adverse effects on vascular patency and post-CPB cardiac function. [ABSTRACT FROM AUTHOR]

The horizontal-to-vertical (H/V) technique by Nakamura (1989) was applied to data from 30 new field stations and 64 other broadband temporary and permanent seismic stations within the Mississippi Embayment of the central United States to develop a 3D model of unconsolidated sediment shear-wave velocity structure. Using the Dart (1992) map of sediment thickness as a basis, two selfconsistent models of average shear-wave velocity versus sediment thickness were developed by utilizing the theoretical linear relationship between the frequency of the H/V peak and shear-wave velocity. One model was based on the observation that the H/V peak period Tp (s) versus sediment thickness h (m) was seen to be approximately linear with the relationship T p = 0.003266h + 1.084. The second model was developed by considering peak frequency f p versus sediment thickness parameterized to follow In /p = 8.325 × 10-7h² - 0.00232h - 0.01796. Overall, the models show low-average shear-wave velocity near the edge of the Mississippi Embayment with velocities increasing with increasing sediment thickness, consistent with increased sediment compaction. These models will be useful in studies of site resonance and amplification for earthquake-shaking hazards and for wave propagation computations for the region. [ABSTRACT FROM AUTHOR]

Objective: The myocardial protective effect of remote ischemic preconditioning has been demonstrated in heterogeneous groups of patients undergoing cardiac surgery. No studies have examined this technique in neonates. The present study was performed to examine the remote ischemic preconditioning efficacy in this high-risk patient group. Methods: A preliminary, randomized, controlled trial was conducted to investigate whether remote ischemic preconditioning in cyanosed neonates undergoing cardiac surgery confers protection against cardiopulmonary bypass. Two groups of neonates undergoing cardiac surgery were recruited for the present study: patients with transposition of the great arteries undergoing the arterial switch procedure and patients with hypoplastic left heart syndrome undergoing the Norwood procedure. The subjects were randomized to the remote ischemic preconditioning or sham control groups. Remote ischemic preconditioning was induced by four 5-minute cycles of lower limb ischemia and reperfusion using a blood pressure cuff. Troponin I and the biomarkers for renal and cerebral injury were measured pre- and postoperatively. Results: A total of 39 neonates were recruited—20 with transposition of the great arteries and 19 with hypoplastic left heart syndrome. Of the 39 neonates, 20 were randomized to remote ischemic preconditioning and 19 to the sham control group. The baseline demographics appeared similar between the randomized groups. The cardiopulmonary bypass and crossclamp times were not significantly different between the 2 groups. The troponin I levels were not significantly different at 6 hours after cardiopulmonary bypass nor were the postoperative inotrope requirements. Markers of renal (neutrophil gelatinase-associated lipocalin) and cerebral injury (S100b, neuron-specific enolase) were not significantly different between the 2 groups. Conclusions: Our data suggest that remote ischemic preconditioning in hypoxic neonates undergoing cardiopulmonary bypass surgery does not provide myocardial, renal, or neuronal protection. Additional studies are needed to examine the relationships among developmental age, hypoxia, and the molecular mechanisms of ischemic preconditioning. [Copyright &y& Elsevier]

Background: Outcomes after operations for bicuspid aortic valve disease in pediatric patients were determined. Methods: Between 1977 and 2011, 146 consecutive patients underwent surgical repair of bicuspid aortic valve. Median age at operation was 207 days (range, 5 days to 16 years). Indication for surgery was stenosis in 113, insufficiency in 25, and both in 8. Valve debridement was done in 76 patients, and complex repairs in 70, including 61 who required addition of pericardial patches, consisting of the creation of a neocommissure in 55, cusp extension in 33, and a perforation repair in 6. The valve was made tricuspid in 38 patients (29 cusp extensions). Results: Twenty-year survival was 88% (95% confidence interval, 73% to 95%). After a mean follow-up of 8 ± 7 years, 35 patients needed a reintervention. Freedom from reintervention at 18 years was 43% (95% confidence interval, 28% to 56%). At the latest follow-up, an additional 13 patients without reoperation had moderate or severe stenosis, and 17 had moderate regurgitation. Seventy-eight patients had an event-free long-term outcome (no reintervention, stenosis, or regurgitation). The only independent predictive factors of an event-free outcome were not having addition of patch material at repair (hazard ratio, 12; p = 0.05) and shorter bypass time (HR, 1.01; p = 0.023). The 10-year freedom from any significant event was 60% (95% confidence interval, 46% to 71%) for those without use of patch material, whereas nearly all those with a patch repair had an adverse event at that time. Conclusions: Outcomes after surgical repair of bicuspid aortic valves in the pediatric population are excellent, especially if the repair can be performed without the addition of patches. Primary repair should be offered because long-lasting results can be achieved if the disease can be relieved by simple procedures. [Copyright &y& Elsevier]

Background: Outcomes after atrioventricular (AV) valve operations in patients with functional single ventricles are unclear. Methods: From 1988 to 2010, 76 consecutive patients with single ventricles underwent AV valve operations for regurgitation at a single institution. Five replacements, 66 repairs, and 5 valve closures were performed at a median age of 1 year (range, 1 day–14 years) on 43 tricuspid, 9 mitral, and 24 common AV valves. Results: Hospital mortality was 17% (13/76). The follow-up was 100% complete. There were 15 late deaths. There were 48 survivors with a mean follow-up of 8.3 ± 6 years. One- and 10-year Kaplan-Meier survival after AV valve operations was 72% (95% confidence interval [CI], 60%–81%) and 61% (95% CI, 48%–71%), respectively. Independent predictors of overall mortality were presence of a common AV valve (p = 0.03), requirement for postoperative mechanical circulatory support (p = 0.02), and timing of valve operations between initial palliation and performance of a bidirectional cavopulmonary shunt (BCPS) (p = 0.047). Ten-year freedom from valve reoperation and from thromboembolic events of hospital survivors was 56% (95% CI, 38%–70%) and 70% (95% CI, 56%–80%), respectively. At last follow-up, 11 of 48 surviving patients (23%) had moderate to severe regurgitation, and pacemaker implantation was required in 6 patients. Only 34 patients reached the stage of Fontan completion. Conclusions: AV valve regurgitation is a considerable burden for the patient with a single ventricle, especially when appearing at a young age. A quarter of patients died within the first year after operation, and they had considerable morbidity in terms of reoperation, thromboembolic events, and pacemaker implantation. Their chances of reaching Fontan completion seemed decreased. [ABSTRACT FROM AUTHOR]

Background: Perioperative brain injury is common in infants undergoing cardiac surgery. Amplitude-integrated electroencephalography (aEEG) provides real-time neurologic monitoring and can identify seizures and abnormalities of background cerebral activity. We aimed to determine the incidence of perioperative electrical seizures, and to establish the background pattern of aEEG, in neonates undergoing Norwood-type palliations for complex congenital heart disease in relation to outcome at 2 years. Methods: Thirty-nine full-term neonates undergoing Norwood-type operations underwent aEEG monitoring before and during surgery and for 72 hours postoperatively. The perfusion strategy included full-flow moderately hypothermic cardiopulmonary bypass with antegrade cerebral perfusion. Amplitude-integrated electroencephalography tracings were reviewed for seizure activity and background pattern. Survivors underwent neurodevelopmental outcome assessment using the Bayley Scales of Infant Development (3rd edition) at 2 years of age. Results: Thirteen (33%) infants had electrical seizures, including 9 with intraoperative seizures and 7 with postoperative seizures. Seizures were associated with significantly increased mortality, but not with neurodevelopmental impairment in survivors. Delay in recovery of the aEEG background beyond 48 hours was also associated with increased mortality and worse motor development. Conclusions: Perioperative seizures were common in this cohort. Intraoperative seizures predominantly affected the left hemisphere during antegrade cerebral perfusion. Delayed recovery in aEEG background was associated with increased risk of early mortality and worse motor development. Ongoing monitoring is essential to determine the longer-term significance of these findings. [ABSTRACT FROM AUTHOR]

Objective: Systemic cooling for cardiopulmonary bypass is widely used to attenuate the systemic inflammatory response syndrome and organ injury in children after open surgery. We compared the effects of moderate (24°C) and mild (34°C) hypothermia during bypass on markers of the systemic inflammatory response syndrome and organ injury, and on clinical outcome after corrective surgery for congenital heart disease. Methods: Sixty-six children (mean age, 6.8 ± 5.7 months; mean weight, 6.2 ± 2.3 kg) were randomized to 24°C or 34°C bypass temperature during cardiac surgery. Perfusion strategies were otherwise strictly identical. Clinical data and blood samples were collected before bypass, 5 minutes after aortic crossclamp release, and 4, 24, and 48 hours after bypass. Patients were followed up until discharge from the hospital. Results: In the 54 children with outcome data, bypass temperature did not influence the duration of mechanical ventilation between the 24°C group and the 34°C group (median [interquartile range] 22 [13–40] hours vs 14 [8–40] hours, P = .14), intensive care unit stay (43 [24–49] hours vs 29 [23–47] hours, P = .79), blood loss (29 [20–38] mL/kg vs 23 [13–38] mL/kg, P = .36), or incidence of postoperative infection (9% vs 11%, P = 1.0). There was no evidence of an influence of bypass temperature on the markers of acute inflammation, innate immune response, organ injury, coagulation, or hemodynamics. Conclusions: There is no evidence that the systemic inflammatory response syndrome and organ injury after pediatric open surgery are influenced by bypass temperature. The routine use of hypothermic bypass may not be warranted in the pediatric population. [ABSTRACT FROM AUTHOR]

Background: Repair of total anomalous pulmonary venous drainage (TAPVD) in neonates remains a challenge as it is often associated with severe obstruction. We describe a large cohort of neonates who underwent TAPVD repair at a single institution. Methods: From 1973 to 2008, 112 patients underwent simple TAPVD surgery during the first month of life. Data collection occurred retrospectively. Results: Preoperative pulmonary venous obstruction (PVO) occurred in 89 (79.5%) patients. There were 12 (10.7%) early deaths. Significant risk factors were bypass time greater than 65 minutes (p = 0.014) and emergent surgery (p = 0.005). Hospital mortality was unchanged throughout the 3 eras (1973 to 1988, 1989 to 1998, 1999 to 2008), despite an increase in patients with preoperative acidosis (p = 0.004) and severe TAPVD obstruction (p = 0.038) during the recent 10 years. There were 6 (6.25%) late deaths within 2 years of repair. Survival at 20 years was 83.4% (95% confidence interval 75 to 89). Risk factors for late death were operative weight 2.5 kg or less (p = 0.004) and postoperative pulmonary hypertensive crisis (p = 0.02). Reoperation for recurrent PVO was required in 13 patients (11.9%). Risk factors were operative weight 2.5 kg or less (p = 0.035) and postoperative pulmonary hypertensive crisis (p = 0.002). Follow-up was 96% complete and survivors (n = 90) were asymptomatic at a median age of 11.7 years. Conclusions: Hospital mortality remained unchanged over the 36-year period. Survival beyond 2 years offers excellent outcome. Risk factors for mortality were the preoperative clinical status, prolonged bypass time, persisting micro-obstruction, and low operative weight. A reduction in mortality will likely require development of effective medical management for patients who have peripheral PVO not amenable to surgical repair. [Copyright &y& Elsevier]

Ambient ground-motion data were collected using phased seismic arrays in fall 2002 and spring 2007 within the Mississippi embayment and at a single station external to the embayment. These data allowed us to determine the wave-field composition of ambient noise for understanding wave-propagation mechanisms giving rise to spectral peaks using Nakamura's HIV technique. Ambient ground motions in the frequency band of 0.1-0.33 Hz (10-3 sec period) were dominated by spatially localized Rayleigh- and Love-wave microseisms generated by high-ocean waves along the North American seaboard in the time periods of analysis. Seismic waves important in forming the H/V peak near 4 sec period are composed of relatively high-phase velocity Rayleigh and Love waves that convert to propagating homogeneous shear waves in the thick unconsolidated sediments of the embayment. The H/V resonant period is controlled by both constructive and destructive interference of these shear waves. A simple relationship for the H/V peak is given using a propagator matrix formulation that predicts the resonance frequency of a layered medium for surface wave motion at the base of the system. The amplitude of the observed H/V peak, however, does not give an accurate estimate of shear-wave amplification because it depends on the slowness of the incident wave. The inconsistency in estimated average shear-wave velocities using the H/V method and differential travel times of local earthquake Sp phases in the Mississippi embayment may be explained by misidentification of Sp-wave conversion points from deeper interfaces. [ABSTRACT FROM AUTHOR]

Centrifugal pump left ventricular assist device is a useful adjunct in pediatric cardiac surgery, as a bridge to recovery, or in some cases, to transplantation. This form of circulatory support may not have the universal applicability of extracorporeal membrane oxygenation, but it is equally or more effective in properly selected patients. The technology for centrifugal pump support is now quite standardized, and the advantages well documented. In this chapter we discuss the problems of indications, case selection, technical aspects of the circuit, and general clinical management. Results since 1989 are also presented. [Copyright &y& Elsevier]

This article describes an unusually well-behaved, unusually well-documented central and eastern United States (CEUS) earthquake sequence. Detailed analysis of regional and local waveform data from the 6 June 2003 Bardwell, Kentucky, earthquake indicates that the mainshock has the seismic moment of M0 1.3 (± 0.5) x 1015 N m (Mw 4.0) and occurred at a depth of about 2 (± 1) km on a near-vertical fault plane. A temporary seismic network recorded 85 aftershocks that delineate an east-trending fault approximately 1 km in length. The hypocenters illuminate a vertical plane between 2.0 and 2.7 km depth. The centroid of the aftershock distribution is at 36.875° N, 89.010° W and a depth of 2.4 km. The aftershock cluster is interpreted as a circular fault area with a radius of 0.44 (± 0.03) km. This source radius yields a static stress drop, Δσ = 67 (± 14) bars for the mainshock. The focal mechanism for the mainshock has strike = 90°, dip = 89°, and rake = - 165° with a subhorizontal P axis trending 135°. A formal stress inversion based on the focal mechanisms of the mainshock and ten aftershocks indicates the maximum compressive stress trends 104° with a plunge of 5°. The local stress field near Bardwell is therefore rotated about 40° clockwise relative to 65° for eastern North America as a whole. The Bardwell earthquakes have the opposite sense of slip to earthquakes with east-trending nodal planes that occur near New Madrid, Missouri. This requires a significant local rotation of the stress field over a distance of 60 km. [ABSTRACT FROM AUTHOR]

From examination of theory and practice, it is observed that strategic environmental assessment (SEA) extends the spatial reach of environmental assessment, providing greater scope for offsetting environmental degradation with environmental enhancement. We label this concurrent enhancement and degradation 'uneven development of the environment. ' We argue this uneven development does not resolve the conflict between economic development and the environment. Instead, SEA displaces and defers the conflict. [ABSTRACT FROM AUTHOR]