Search

The primary objectives of this study were to describe the characteristics and survival outcomes for children supported with the HeartWare HVAD® system from the global community. This was a retrospective survey of patients <18 years of age with an HVAD® system. Questionnaires were sent to sites worldwide in April 2015 and collected between May 2015 and 2016. Information on 205 patients was collected. The median age at implantation was 13.1 years (interquartile range [IQR] 9.8-15.8 years) and the weight was 42 kg (IQR 28-60 kg). Over half of the implants occurred in males (61%), with the most common diagnosis being cardiomyopathy (n = 168, 82%). The majority of HVAD® systems implanted were left ventricular assist device (n = 189, 92.2%). Temporary right ventricular support was utilized in 24 patients (12%) with a median duration of 12 days (6-32 days). Fifty-five percent (n = 111) of the patients were discharged home after implantation after a median (IQR) duration of hospital stay of 40 days (28-71 days). By 12 months, the proportion of patients who underwent heart transplant was 65.4%, 10.7% had died, 3.2% were explanted for recovery, and 20.8% remained on the device. Death on the device on multivariable analysis was associated with the need for temporary RV support (hazard ratio [HR] 10.65 (95% CI 12.53-44.81), P = 0.001) and pump exchange (HR 7.9 (95% CI 1.8-34.2], P = 0.006). The use of the HeartWare HVAD system in the pediatric population is associated with mortality with the majority of patients supported to heart transplant by 1 year post implant. These positive results are independent of geographic location. The need for a temporary right heart support and pump exchange is associated with a higher risk of poor outcomes, and further work is required to predict these patients to allow for optimization. Although survival results are promising, further studies are needed to delineate the associated morbidities with this technology in the pediatric population. [ABSTRACT FROM AUTHOR]

Children and adolescents with high functioning autism (HFA) display heterogeneity in social competence, which may be particularly evident during interactions with unfamiliar peers. The goal of this study was to examine predictors of social competence variability during an unfamiliar peer interaction. Thirty-nine participants with HFA and 39 age-, gender- and IQ-matched comparison participants were observed during dyadic laboratory interactions and detailed behavioral coding revealed three social competence dimensions: social initiative , social reciprocity , and social self-monitoring . Participants with HFA displayed higher social initiative but lower reciprocity than comparison participants. For participants with HFA, theory of mind was positively associated with observed initiative. For COM participants, social anxiety was negatively associated with reciprocity. However, for HFA participants, there was a quadratic relation between parent-reported social anxiety and observed reciprocity, demonstrating that low and high levels of anxiety were associated with low reciprocity. Results demonstrated the utility of our behavioral coding scheme as a valid assessment of social competence for children and adolescents with and without HFA. The curvilinear association between social anxiety and reciprocity highlights the importance of examining nonlinear relations in individuals with HFA, and emphasizes that discrete profiles of social anxiety in individuals with HFA may necessitate different treatment options. [ABSTRACT FROM AUTHOR]

Background: ABO incompatible (ABOi) heart transplantation is an accepted approach to increasing organ availability for young patients. Previous studies have suggested that early survival for ABOi transplants is similar to ABO compatible (ABOc) transplants. We analyzed the Pediatric Heart Transplant Study (PHTS) database from 1/96 to 12/08 to further assess this strategy. Methods: We analyzed the numbers of ABOi and ABOc done at the PHTS centers. We then compared the clinical characteristics, and short-term freedom from death, rejection and infection in the ABOi patients with the patients that had an ABOc heart transplant during the same period. All patients were less than or equal to 15 months of age at listing (the age of the oldest ABOi patient). We adjusted for co-variates shown to increase risk for mortality (age less than 1 month, extracorporeal membrane oxygenation (ECMO), ventilator, previous sternotomy, and congenital heart disease). Results: There were 931 total transplants done at 34 PHTS centers during the 12 year time period in patients ≤15 months of age. Of these, 502 transplants were performed at 20 PHTS centers that did at least one ABOi heart transplant. Eighty-five of the 502 (17%) were ABOi. At time of transplant, ABOi recipients compared with ABOc were more likely to be on a ventilator (49.4% vs 36.5%, p=0.025), and more often supported with ECMO (23.5% vs 13.4%, p=0.018). There was similar survival at 12 months (82% vs 84%, p=0.7). In risk adjusted analysis ABOi status was not associated with 1 year mortality (HR 0.85, 95% CI 0.45–1.6, p=0.61). The ABOi patients had greater freedom from rejection when compared with ABOc patients for all 34 centers (75% vs 62%, p=0.016), but the difference was not significant when limited only to the 20 centers doing ABOi transplants (75% vs 69%, p=0.4). The ABOi cohort had lower infection rates (23.5% vs 37.9%, p = 0.013). This difference remained after adjusting for center and other covariates. Conclusions: In center and risk adjusted analysis, young children who received an ABOi transplant had equivalent one-year survival and freedom from rejection compared with those who received an ABOc transplant. In spite of the favorable outcome for ABOi recipients, many centers appear to reserve ABOi transplantation for sicker patients. These data mandate reexamination of the current United Network for Organ Sharing (UNOS) policy that gives priority to ABOc over ABOi transplantation in the United States. [ABSTRACT FROM AUTHOR]

Abstract: Oral vaccination is an important part of wildlife rabies control programs. Currently, the vaccinia-rabies glycoprotein recombinant virus is the only oral rabies vaccine licensed in the United States, and it is not effective in skunks. In the current study, captive raccoons and skunks were used to evaluate a vaccine developed by incorporating the rabies virus glycoprotein gene into a canine adenovirus serotype 2 vector (CAV2-RVG). Seven of 7 raccoons orally vaccinated with CAV2-RVG developed virus neutralizing antibodies and survived lethal challenge. Five of 5 and 6 of 6 skunks in 2 experimental groups receiving 10-fold different dilutions of CAV2-RVG developed neutralizing antibodies and survived challenge. The results of this preliminary study suggest that CAV2-RVG stimulates protective immunity against rabies in raccoons and skunks. [Copyright &y& Elsevier]

Presents a study which examined the influence of maternal reports of negative reactivity in the first year of life on measures of sociability and social wariness taken at four years of age. Gender differences in social wariness; Methodology and results; Limitations of the study; Clinical implications.

Heart failure results in significant morbidity and mortality for young children with hypoplastic left heart syndrome (HLHS) following the Norwood procedure. The trajectory in later childhood is not well described. We studied the outcome into adolescence of participants enrolled in the Single Ventricle Reconstruction trial who underwent the Fontan procedure or survived to 6 years without having undergone Fontan procedure. The primary outcome was heart failure events, defined as heart transplant listing or death attributable to heart failure. Symptomatic heart failure for participants surviving 10 or more years was also assessed utilizing the Pediatric Quality of Life Inventory (PedsQL). Of the 345 participants who underwent a Fontan operation or survived to 6 years without Fontan, 25 (7.2%) had a heart failure event before the age of 12 years. Among these, 21 were listed for heart transplant, and 4 died from heart failure. Nineteen participants underwent heart transplant, all of whom survived to age 12 years. Factors associated with a heart failure event included longer Norwood hospital length of stay, aortic atresia, and no Fontan operation by age 6 years. Assessment of heart failure symptoms at 12 years of age revealed that 24 (12.2%) of 196 PedsQL respondents "often" or "almost always" had difficulty walking more than one block. Heart failure events occur in over 5% of children with palliated HLHS between preschool age and adolescence. Outcomes for children listed for transplant are excellent. However, a substantial portion of palliated HLHS children have significant symptoms of heart failure at 12 years of age. [ABSTRACT FROM AUTHOR]

Background In the Single Ventricle Reconstruction trial, infants with hypoplastic left heart syndrome (HLHS) who received a right-ventricle-to-pulmonary-artery shunt (RVPAS) versus a modified Blalock-Taussig shunt (MBTS) had lower early postoperative mortality, but more complications at 14 months. We explored the effect of shunt type and other patient, medical, and surgical factors on postoperative length of stay (LOS) after the Fontan operation. Methods Fontan postoperative course was ascertained from medical record review. Cox proportional hazards modeling was used to identify factors associated with LOS. Results Of 327 subjects who underwent Fontan, 323 were analyzed (1 death, 1 biventricular repair, 2 with missing data). Median age and weight at Fontan were 2.8 years (interquartile range [IQR]: 2.3, 3.4) and 12.7 kg (IQR: 11.4, 14.1), respectively. Fontan type was extracardiac in 55% and lateral tunnel in 45%; 87% were fenestrated. The RVPAS and MBTS subjects had similar LOS (median 11 days [IQR: 9, 18] vs 10 days [IQR: 9, 13]; P = .23). Independent risk factors for longer LOS were treatment center ( P < .01), LOS at stage II (hazard ratio [HR] 1.02 for each additional day; P < .01), and pre-Fontan complications (HR 1.03 for each additional complication; P = .04). Use of deep hypothermic circulatory arrest at Fontan (HR 0.64; P = .02) was independently associated with shorter LOS. When center was excluded from the model, pre-Fontan complications and use of circulatory arrest were no longer significant; instead, older age at stage II (HR 1.08 for each additional month; P = .01) predicted longer LOS. In 254 subjects who had a pre-Fontan echocardiogram, at least moderate tricuspid regurgitation was independently associated with longer LOS, both with center (HR 1.72; P < .01) and without center in the model (HR 1.49; P = .02). Conclusions In this multicenter prospective cohort of subjects with HLHS, Norwood shunt type was not associated with Fontan LOS. Rather, global measures of earlier medical complexity indicate greater likelihood of longer LOS after the Fontan operation. [ABSTRACT FROM AUTHOR]

Objective: Behavioral inhibition (BI) is an infant temperament characterized by heightened reactivity and negative affect in response to novel people and situations. BI is among the earliest and strongest predictors of future anxiety problems. However, not all children with a history of BI will manifest anxiety problems. A growing body of evidence suggests that proactive control skills may help buffer youth with BI from future anxiety difficulties; yet, it remains unclear how temperament may interact with the development of cognitive control to influence anxiety risk. The present study tested whether enhancements in proactive control occurring during adolescence may reduce risk for anxiety among youth with a history of BI.Method: Participants included 185 adolescents (56% female) whose temperament was assessed during toddlerhood. In adolescence, participants completed anxiety assessments and an AX Continuous Performance Test (AX-CPT) to assess cognitive control strategy. Both assessments were administered at age 13 years and again at 15 years.Results: Latent change score modeling revealed that, on average, participants increasingly used proactive control strategies and experienced worsening anxiety from age 13-15 years. Early BI was associated with a smaller anxiety increase from 13-15 years, but only among participants whose proactive control skills improved at mean or greater rates.Conclusion: The present findings suggest that greater proactive control development during adolescence protects youth with high BI from age-related increases in anxiety. Results support a framework that highlights cognitive control as a key moderator of anxiety risk among children with a history of high BI. [ABSTRACT FROM AUTHOR]

Temperament involves stable behavioral and emotional tendencies that differ between individuals, which can be first observed in infancy or early childhood and relate to behavior in many contexts and over many years.1 One of the most rigorously characterized temperament classifications relates to the tendency of individuals to avoid the unfamiliar and to withdraw from unfamiliar people, objects, and unexpected events. This temperament is referred to as behavioral inhibition or inhibited temperament (IT).2 IT is a moderately heritable trait1 that can be measured in multiple species.3 In humans, levels of IT can be quantified from the first year of life through direct behavioral observations or reports by caregivers or teachers. Similar approaches as well as self-report questionnaires on current and/or retrospective levels of IT1 can be used later in life. [ABSTRACT FROM AUTHOR]

Abstract: While current rabies post-exposure prophylaxis (PEP) is highly effective, it is costly and the vaccination regimen is complicated, requiring both inactivated vaccines and immunoglobulins. A one-dose rabies vaccine for human PEP remains a long-term goal. Here, we describe development of a highly attenuated rabies virus ERAg3m, with a mutation in the glycoprotein (G) gene and a switch of the G gene with the matrix protein gene in the viral genome. After a one-dose intramuscular vaccination, the ERAg3m virus protected 100% of mice and hamsters from lethal challenge. In co-infections, using a lethal dose of street rabies virus mixed with ERAg3m, 100% of hamsters and 90% of mice survived and were protected against subsequent infection. A mock co-infection, using inactivated commercial human rabies vaccine and a lethal dose of street rabies virus, protected 100% and 40% of hamsters and mice, respectively. In co-infections, when vaccine was administrated in the left leg and challenge virus in the right leg, the ERAg3m virus protected 40% of mice, while the inactivated vaccine showed no protection. Therefore, live attenuated rabies virus when given pre-exposure or co-infected with street rabies virus, is capable of preventing rabies in two different animal models. Overall, this highly attenuated live rabies virus offered better protection than the inactivated vaccine. [Copyright &y& Elsevier]

Background: Behaviorally inhibited (BI) children who also exhibit enhanced response monitoring might be at particularly high risk for anxiety disorders. The current study tests the hypothesis that response monitoring, as manifest in the error-related negativity (ERN), moderates the association between BI and anxiety. Methods: Participants (n = 113; 73 male) assessed for early-childhood BI were re-assessed as adolescents with a clinical interview and a flanker paradigm that generated behavioral data and event-related potentials (ERPs). Risk for anxiety disorders in adolescents was examined as a function of childhood-BI status and adolescent performance on the flanker paradigm. Results: Adolescents with childhood BI displayed ERP evidence of enhanced response monitoring, manifest as large ERNs. The ERN moderated the relationship between early BI and later clinically significant disorders. Conclusions: Physiological measures of response monitoring might moderate associations between early-childhood BI and risk for psychopathology. The subset of children with BI and enhanced response monitoring might face greater risk for later-life clinical anxiety than children with either BI or enhanced response monitoring alone. [Copyright &y& Elsevier]

Summary: Behavioral problems in young children can take on a variety of forms, which are linked to distinct antecedents and co-occurring markers. Internalizing difficulties in young children, for example, have been linked to individual differences in infant temperament and cortisol levels. In addition, there is growing evidence that these biobehavioral mechanisms are also shaped by gender. Four-year-old children participated in a study examining the relations between salivary cortisol and behavioral maladjustment as a function of gender and temperament. Both longitudinal (maternal report of infant temperament at 9 months) and concurrent (morning salivary cortisol at age 4) data were used to predict two forms of maladjustment: ‘Withdrawal’ (maternal report of internalizing behavior and laboratory observation of social reticence) and ‘Acting Out’ (maternal report of externalizing behavior and laboratory observation of solitary active play). High basal cortisol levels were strongly associated with Withdrawal in male participants. However, the relation was significant only in boys who exhibited high levels of negative temperament in infancy. There were no comparable findings with ‘Acting Out’ beyond a main effect of gender reflecting greater difficulty in boys. The data suggested that there are unique biobehavioral mechanisms shaping specific patterns of maladjustment in childhood. [Copyright &y& Elsevier]

Abstract: The purpose of the current study is to describe the development and validation of a new measure of temperament, the Preschool Temperament Classification System (PTCS). The PTCS was developed as a typological measure that identifies children''s temperament styles as undercontrolled, resilient, or overcontrolled. The PTCS is a time efficient structured interview assessing children''s temperament as it is observed in the classroom environment. During the 20min interview, teachers classify all of the children in their class into one of the three temperament styles, rank order children within each temperament group, and assign an intensity rating to each child, indicating how well the child matches his/her assigned temperament group. Data were collected on 196 preschool-age children from 25 Head Start classrooms in an urban area. Teachers assessed children''s temperament and peer play behaviors, and trained research assistants assessed children''s school readiness. The PTCS classified children into temperament groups that showed expected relations to peer play competence and school readiness after controlling for age and gender, indicating good validity. Test–retest reliability was moderate to high. Overall the PTCS shows promise as a valid and reliable teacher measure of preschool children''s temperament. [Copyright &y& Elsevier]

Objective: The COVID-19 pandemic has brought unprecedented changes to young adults' lives, resulting in mental health difficulties for many; however, some individuals are particularly prone to heightened anxiety. Little is known about the early life predictors of anxiety during the pandemic. We examined a developmental pathway from behavioral inhibition (BI), a temperament characterized by fearful responses toward novelty, to changes in young adults' anxiety during the initial period of the pandemic. We hypothesized that a stable pattern of BI across early childhood would predict greater adolescent worry dysregulation, which in turn would predict increases in young adult anxiety during a stressful phase of the pandemic.Method: Participants (N = 291; 54% female) were followed from toddlerhood to young adulthood. BI was observed at ages 2 and 3 years. Social wariness was observed at age 7 years. Participants rated their worry dysregulation in adolescence (age 15) and anxiety in young adulthood (age 18) at 2 assessments during the COVID-19 pandemic, 1 month apart.Results: A significant moderated mediation, in which a stable pattern of BI from toddlerhood to childhood, as compared to the absence of this pattern, predicted greater worry dysregulation in adolescence. Worry dysregulation predicted elevated young adult anxiety in the second assessment during COVID-19, even after accounting for the first assessment.Conclusion: This study identifies a developmental pathway from toddlerhood BI to young adults' elevated anxiety during the COVID-19 pandemic. Findings have implications for early identification of individuals at risk for dysregulated worry and the prevention of anxiety during stressful life events in young adulthood. [ABSTRACT FROM AUTHOR]

• Phase 1 study of HEPLISAV-B in hemodialysis patients. • Four doses of HEPLISAV-B induced high level of seroprotection and were well tolerated. Hemodialysis patients are at increased risk of hepatitis B virus (HBV) infection and are poorly responsive to HBV vaccines. Current vaccine recommendations for hemodialysis patients utilize more than twice the amount of hepatitis B surface antigen (HBsAg) used for healthy adults and achieve lower immune responses. An open-label, single-arm, multicenter trial was conducted among adults 18 years of age and older who were initiating or undergoing hemodialysis who had not previously received hepatitis B vaccine. Participants received four doses of HepB-CpG (HEPLISAV-B®) (20 mcg rHBsAg + 3000 mcg CpG 1018, a Toll-like receptor 9 agonist) administered at 0, 4, 8, and 16 weeks. Participants are being followed for 68 weeks. This paper reports the final immunogenicity analysis of the primary endpoint at study week 20 and an interim safety analysis. We enrolled 119 participants receiving hemodialysis who were followed for a median of 47.4 weeks. Of the 119 participants, 75 were in the per-protocol population. At week 20, the seroprotection rate (% with antibodies to hepatitis B surface antigen [anti-HBs] ≥ 10 mIU/mL) was 89.3% and the percentage of participants with anti-HBs ≥ 100 mIU/mL was 81.3%. The anti-HBs geometric mean concentration was 1061.8 mIU/mL. HepB-CpG was well tolerated with no observed safety concerns. In patients receiving hemodialysis, HepB-CpG given as four doses was well tolerated and induced very high anti-HBs concentrations and seroprotection in a very high proportion of recipients. [ABSTRACT FROM AUTHOR]

Behavioral inhibition (BI) is a temperament characterized in early childhood by distress to novelty and avoidance of unfamiliar people, and it is one of the best-known risk factors for the development of social anxiety. However, nearly 60% of children with BI do not go on to meet criteria for social anxiety disorder. In this review we present an approach to understanding differential developmental trajectories among children with BI. We review research using laboratory-based tasks that isolate specific attention processes that enhance versus mitigate risk for social anxiety among behaviorally inhibited children and studies that suggest that BI is associated with heightened detection of novelty or threat. Moreover, stimulus-driven control processes, which we term "automatic control," increase the probability that behaviorally inhibited children display socially reticent behavior and develop social anxiety. In contrast, goal-driven control processes, which we term "planful control," decrease risk for anxiety. We suggest that these three categories of processes (detection, automatic control, and planful control) function together to determine whether behaviorally inhibited children are able to flexibly regulate their initial reactions to novelty, and in turn, decrease risk for social anxiety. Although laboratory-based tasks have identified these processes underlying risk and resilience, the challenge is linking them to the emotions, thoughts, and behaviors of behaviorally inhibited children in real-world contexts. [ABSTRACT FROM AUTHOR]

BACKGROUND Rejection with severe hemodynamic compromise (RSHC) carries a mortality risk approaching 50%. We aimed to identify current risk factors for RSHC and predictors of graft failure after RSHC. METHODS Data from 3,259 heart transplant (HT) recipients between January 2005 and December 2015 in the Pediatric Heart Transplant Study (PHTS) were analyzed. Predictors for RSHC and outcome after RSHC were sought. Time to RSHC was analyzed using the Cox proportional hazards regression model. Cardiac allograft vasculopathy (CAV) after HT and CAV after RSHC were analyzed as time-dependent covariates. Timing of RSHC was analyzed as occurring before and after 4 years after RSHC. RESULTS There were 309 patients (9.5%) with ≥ 1 RSHC episodes. In 143 patients with RSHC, the first episode was within 1 year after HT. Independent risk factors for RSHC were age 1 to 5 years at HT (hazard ratio [HR], 1.51; 95% confidence interval [CI], 1.04–2.18), age > 10 years at HT (HR, 1.83; 95% CI, 1.29–2.60), black race (HR, 1.64; 95% CI, 1.25–2.15), prior cardiac surgery (HR, 1.55; 95% CI, 1.03–2.31), ventricular assist device support at HT (HR, 1.65; 95% CI, 1.18–2.29), maintenance steroids (HR, 1.39; 95% CI, 1.06–1.82), and recipient on inotropes, pressors, or thyroid hormones (HR, 1.45; 95% CI, 1.09–1.94). Graft survival at 5 years after RSHC was 45.7%. RSHC was a greater risk factor for earlier CAV (HR, 7.78; 95% CI, 5.82–10.40) than other rejection types (HR, 2.31; 95% CI, 1.79–3.00). Patients with late RSHC, after 1 year after RSHC had increased risk of graft loss 4 years after RSHC (HR, 7.12; 95% CI, 2.18–23.22). The 5-year graft survival after RSHC was 50.5% for early RSHC and 39.0% for late RSHC. CONCLUSIONS Mortality after RSHC is high in the current treatment era. Many patient risk factors for RSHC cannot be modified, including age, race, prior cardiac surgery, and ventricular assist device support. After RSHC, CAV is the only predictor of graft failure. Patients who have late RSHC fare worse than those who have RSHC within the first year after HT. [ABSTRACT FROM AUTHOR]

Background Heart failure results in significant morbidity and mortality in young children with hypoplastic left heart syndrome (HLHS) after the Norwood procedure. Methods We studied subjects enrolled in the prospective Single Ventricle Reconstruction (SVR) Trial who survived to hospital discharge after a Norwood operation and were followed up to age 6 years. The primary outcome was heart failure, defined as heart transplant listing after Norwood hospitalization, death attributable to heart failure, or symptomatic heart failure (New York Heart Association [NYHA] Class IV). Multivariate modeling was undertaken using Cox regression methodology to determine variables associated with heart failure. Results Of the 461 subjects discharged home following a Norwood procedure, 66 (14.3%) met the criteria for heart failure. Among these, 15 died from heart failure, 39 were listed for transplant (22 had a transplant, 12 died after listing, and 5 were alive and not yet transplanted), and 12 had NYHA Class IV heart failure but were never listed. The median age at heart failure identification was 1.28 (interquartile range 0.30 to 4.69) years. Factors associated with early heart failure included post-Norwood lower fractional area change, need for extracorporeal membrane oxygenation, non-Hispanic ethnicity, Norwood perfusion type, and total support time ( p < 0.05). Conclusions By 6 years of age, heart failure developed in nearly 15% of children after the Norwood procedure. Although transplant listing was common, many patients died from heart failure before receiving a transplant or without being listed. Shunt type did not impact the risk of developing heart failure. [ABSTRACT FROM AUTHOR]

Communicative abilities play a crucial role in children's social success and, for shyer children, protect against socio-emotional maladjustment. Despite communication being highly reciprocal, research on the dyadic influences of children's shyness on their own and their partner's communicative behaviours is limited. Addressing this gap, children (M age = 10.07 years; N = 338) were paired with a same-sex and same-age, unfamiliar peer and completed two puzzle tasks wherein one child ("instructor") could only see the puzzle, while the other child ("listener") could only move the pieces. Children's communicative behaviours were observed, with children switching roles between trials. Shyer instructors verbalized fewer instructions and received less encouragement from listeners during puzzle one. During puzzle two, shyer instructors verbalized fewer instructions and received more responses from listeners, while shyer listeners verbalized less encouragement. Findings provide insight into how temperamental shyness influences interactions within a structured communicative setting. • Examined the dyadic effect of shyness on children's own and their social partners' communicative behaviours. • Used a relevant context for school-aged children: a collaborative, goal-directed task with specific communicative roles ("instructor" and "listener"). • Shyer children produced fewer instructional statements when in instructor role. • Children attuned their communicative behaviours to the shy temperament of their unfamiliar social partner. • Dyadic association between shyness and communication varied by social role and experience with the task. [ABSTRACT FROM AUTHOR]

Objective: Behavioral inhibition (BI) is a temperament identified in early childhood that is a risk factor for later social anxiety. However, mechanisms underlying the development of social anxiety remain unclear. To better understand the emergence of social anxiety, longitudinal studies investigating changes at behavioral neural levels are needed.Method: BI was assessed in the laboratory at 2 and 3 years of age (N = 268). Children returned at 12 years, and an electroencephalogram was recorded while children performed a flanker task under 2 conditions: once while believing they were being observed by peers and once while not being observed. This methodology isolated changes in error monitoring (error-related negativity) and behavior (post-error reaction time slowing) as a function of social context. At 12 years, current social anxiety symptoms and lifetime diagnoses of social anxiety were obtained.Results: Childhood BI prospectively predicted social-specific error-related negativity increases and social anxiety symptoms in adolescence; these symptoms directly related to clinical diagnoses. Serial mediation analysis showed that social error-related negativity changes explained relations between BI and social anxiety symptoms (n = 107) and diagnosis (n = 92), but only insofar as social context also led to increased post-error reaction time slowing (a measure of error preoccupation); this model was not significantly related to generalized anxiety.Conclusion: Results extend prior work on socially induced changes in error monitoring and error preoccupation. These measures could index a neurobehavioral mechanism linking BI to adolescent social anxiety symptoms and diagnosis. This mechanism could relate more strongly to social than to generalized anxiety in the peri-adolescent period. [ABSTRACT FROM AUTHOR]

Background: Multicenter longitudinal objective data for survival into adulthood of patients who have undergone Fontan procedures are lacking.Objectives: This study sought to describe transplant-free survival and explore relationships between laboratory measures of ventricular performance and functional status over time.Methods: Exercise testing, echocardiography, B-type natriuretic peptide, functional health assessment, and medical history abstraction were repeated 9.4 ± 0.4 years after the Fontan Cross-Sectional Study (Fontan 1) and compared with previous values. Cox regression analysis explored risk factors for interim death or cardiac transplantation.Results: From the original cohort of 546 subjects, 466 were contacted again, and 373 (80%) were enrolled at 21.2 ± 3.5 years of age. Among subjects with paired testing, the percent predicted maximum oxygen uptake decreased (69 ± 14% vs. 61 ± 16%; p < 0.001; n = 95), ejection fraction decreased (58 ± 11% vs. 55 ± 10%; p < 0.001; n = 259), and B-type natriuretic peptide increased (median [interquartile range] 13 [7 to 25] pg/mol vs. 18 [9 to 36] pg/mol; p < 0.001; n = 340). At latest follow-up, a lower Pediatric Quality of Life Inventory physical summary score was associated with poorer exercise performance (R2 adjusted = 0.20; p < 0.001; n = 274). Cumulative complications since the Fontan procedure included additional cardiac surgery (32%), catheter intervention (62%), arrhythmia treatment (32%), thrombosis (12%), and protein-losing enteropathy (8%). Since Fontan 1, 54 subjects (10%) have received a heart transplant (n = 23) or died without transplantation (n = 31). The interval risk of death or/cardiac transplantation was associated with poorer ventricular performance and functional health status assessed at Fontan 1, but it was not associated with ventricular morphology, the subject's age, or the type of Fontan connection.Conclusions: Interim transplant-free survival over 12 years in this Fontan cohort was 90% and was independent of ventricular morphology. Exercise performance decreased and was associated with worse functional health status. Future interventions might focus on preserving exercise capacity. (Relationship Between Functional Health Status and Ventricular Performance After Fontan-Pediatric Heart Network; NCT00132782). [ABSTRACT FROM AUTHOR]

Background Traditionally, an elevated pulmonary vascular resistance index (PVRI) has been a relative contraindication to pediatric orthotopic heart transplantation. This study examined the risk of elevated pre-transplant PVRI on early (30-day) and intermediate-term mortality in pediatric heart transplant recipients without congenital heart disease (CHD). Methods A review of the prospective multicenter Pediatric Heart Transplant Study registry identified all patients without CHD in whom a pre-transplant PVRI was recorded. Of 35 participating centers, 29 reported heart transplants in children with a markedly elevated PVRI (> 5 WU × m 2 , corresponding to the highest quartile). Multiphase parametric analysis was performed, adjusting for potential risk factors to assess the association of PVRI with early and intermediate-term mortality. Results Between 1993 and 2011, 1,909 children without CHD underwent heart transplantation at a median age of 9.7 years (range, 1.6 months–18 years). Of those, 795 (42%) had a recorded or calculable pre-transplant PVRI, and PVRI > 5 WU × m 2 was present in 193 patients (24%). For all recipients, median pre-transplant PVRI was 3.15 WU × m 2 (range, 0.4–23 WU × m 2 ); 2.8 WU × m 2 in infants < 1 year, 3.5 WU × m 2 in patients aged 1 to 10 years, and 3.0 WU × m 2 in patients aged > 10 years ( p = 0.03). Multivariable hazard analysis controlling for graft ischemic time and pre-transplant ventilation showed no association of elevated PVRI with early mortality (relative risk, 1.2; p = 0.66), nor with intermediate mortality when controlled for year of transplant, age, race, and pre-sensitization (relative risk, 0.7; p = 0.27). Conclusions Elevation of PVRI did not affect post-transplant survival in this large, multicenter cohort of pediatric heart transplant recipients without CHD, suggesting that the barrier of elevated PVRI can be successfully overcome in this population. [ABSTRACT FROM AUTHOR]

Objective: Behavioral inhibition (BI) is an early childhood temperament characterized by fearful responses to novelty and avoidance of social interactions. During adolescence, a subset of children with stable childhood BI develop social anxiety disorder and concurrently exhibit increased error monitoring. The current study examines whether increased error monitoring in 7-year-old, behaviorally inhibited children prospectively predicts risk for symptoms of social phobia at age 9 years. Method: A total of 291 children were characterized on BI at 24 and 36 months of age. Children were seen again at 7 years of age, when they performed a Flanker task, and event-related potential (ERP) indices of response monitoring were generated. At age 9, self- and maternal-report of social phobia symptoms were obtained. Results: Children high in BI, compared to those low in BI, displayed increased error monitoring at age 7, as indexed by larger (i.e., more negative) error-related negativity (ERN) amplitudes. In addition, early BI was related to later childhood social phobia symptoms at age 9 among children with a large difference in amplitude between ERN and correct-response negativity (CRN) at age 7. Conclusions: Heightened error monitoring predicts risk for later social phobia symptoms in children with high BI. Research assessing response monitoring in children with BI may refine our understanding of the mechanisms underlying risk for later anxiety disorders and inform prevention efforts. [ABSTRACT FROM AUTHOR]

Abstract: The purpose of this study was to examine developmental change and the influence of shyness on social problem-solving (SPS). At 24, 36, and 48months, children (N=570) were observed while interacting with an unfamiliar peer during an SPS task and at 24months, maternal report of shyness was collected. Results showed that across the full sample, children displayed low but stable levels of withdrawn SPS and increasing levels of SPS competence over development. In addition, results showed multiple trajectories of withdrawn and competent SPS. Shyness was associated with high-increasing and high-decreasing withdrawn SPS trajectories compared with the low-increasing withdrawn SPS trajectory. Shyness was also associated with the low-increasing compared with the high-increasing SPS competence trajectory. Findings demonstrate the development of SPS competence over early childhood, and the influence of early shyness on this developmental course, with some shy children showing improvement in SPS skills and others continuing to show SPS difficulties over time. [Copyright &y& Elsevier]

Abstract: One hundred thirty seven adolescents (M =15.3yrs, SD =1.0yr, n =72 girls) were recruited into temperament groups when they were 4months of age based on reactivity to novel auditory/visual stimuli (Fox, Henderson, Rubin, Calkins, & Schmidt, 2001). Behavioral inhibition was observed across infancy (14 and 24months). Additionally, self-reported substance-related problems and behavioral risk-taking was assessed during adolescence. High behavioral inhibition increased risk for substance-related problems among boys, whereas high behavioral inhibition protected against substance-related problems among girls, B =−1.18, SE =.48, 95% CI=−2.13 to −.24; p <.05. Additionally, high behavioral inhibition protected lower risk-taking children from adolescent substance-related problems whereas high behavioral inhibition increased risk for substance-related problems among higher risk-taking children, B =.04, SE =.02, 95% CI=.00 to .08. Findings from this prospective, multi-informant, longitudinal study suggest that risk-taking and gender may interact with temperamental traits to place adolescents at differential risk for substance-related related behavior problems. [ABSTRACT FROM AUTHOR]

Abstract: Despite progress in vaccine development in the past century the mechanisms behind immune responses elicited by rabies biologics or via natural infection remain largely unknown. In this study, we compared protection elicited by standard, early, or delayed prophylaxis with a reduced number of vaccine doses using inactivated and live-attenuated vaccines. Two-month-old Syrian hamsters, 4-week-old ICR mice or adult rhesus macaques were inoculated with canine rabies virus variants. Thereafter, prophylaxis was initiated 6h, 1, 2, 3, 4, 5, 6 or 7 days post-exposure (p.e.). One or several doses of inactivated (HDCV), or reverse genetically attenuated (live), or gamma-irradiated (inactivated)-ERAG333 vaccines were administered intramuscularly. The dynamics of virus spread were measured over time in the rodent models. Rabies virus reached the spinal cord at day 4 and brain at day 6 p.e. All hamsters succumbed in groups in which live ERAG333 was delayed until days 5 and 6 p.e. However, 78%, 44%, 56% and 22% of hamsters survived when one dose of live ERAG333 was administered 6h, 1, 2, 3, and 4 days p.e., respectively. Similarly, 67% survived when inactivated ERAG333 was administered at 24h p.e. All hamsters succumbed when standard prophylaxis (the Essen regimen) was delayed until days 3–6, but 67% and 33% of hamsters survived when PEP began 1 or 2 days p.e., respectively. Macaques were protected by one dose of attenuated ERAG333 at 24h p.e. The highly attenuated (live) and inactivated ERAG333 vaccines elicited potent protective immune responses, even when prophylaxis initiation was delayed. When 2–5 doses of commercial vaccine and HRIG were administered according to the Essen scheme, 89–100% of the animals survived. Reduced vaccine schedules provided efficacious intervention, regardless of the total number of vaccine doses administered. [Copyright &y& Elsevier]

The article presents a study which predicts the link between behavioral inhibition (BI) and anxiety disorders such as social anxiety disorder (SAD) in later life. Participants in the study include 126 adolescents aged 14 to 16 years who were recruited when they were still four months old and temperaments were measured when they were between the ages of 14 months and 7 years. The findings suggest that stable maternal-reported early BI is significant in identifying and preventing SAD.

The article focuses on a study which examines whether startle reflex responses differ between behaviorally inhibited (BI) adolescents with anxiety disorders compared to those who do not. The study identifies behavioral or physiological markers which may be used to differentiate between BI adolescents with and without anxiety disorders. Results of the study show that the startle response in adolescents posts a high risk for anxiety disorder development, and its pattern is suggestive of abnormal inhibitory fear process.

Objective: Children with the temperament of behavioral inhibition (BI) face increased risk for developing an anxiety disorder later in life. However, not all children with BI manifest anxiety symptoms, and use of a cognitive control strategy could moderate the pathway between BI and anxiety. Individuals vary widely in the strategy used to instantiate control. The present study examined whether a more planful style of cognitive control (ie, proactive control) or a more impulsive strategy of control (ie, reactive control) would moderate the association between early BI and later anxiety symptoms.Method: Participants were part of a longitudinal study examining the relations between BI (measured at 2-3 years of age) and later anxiety symptoms (measured at 13 years). Use of a cognitive control strategy was assessed at 13 years using the AX variant of the continuous performance task.Results: BI in toddlerhood significantly predicted increased use of a more reactive cognitive control style in adolescence. In addition, cognitive control strategy moderated the relation between BI and anxious symptoms, such that reliance on a more reactive strategy predicted higher levels of anxiety for children high in BI.Conclusion: The present study is the first to identify the specific control strategy that increases risk for anxiety. Thus, it is not cognitive control per se, but the specific control strategy children adopt that could increase risk for anxiety later in life. These findings have important implications for future evidence-based interventions because they suggest that an emphasis on decreasing reactive cognitive control and increasing proactive cognitive control might decrease anxious cognition. [ABSTRACT FROM AUTHOR]

Objective: Behavioral inhibition (BI) during early childhood predicts risk for anxiety disorders and altered cognitive control in adolescence. Although BI has been linked to variation in brain function through adulthood, few studies have examined relations between early childhood BI and adult brain structure.Method: The relation between early childhood BI and cortical thickness in adulthood was examined in a cohort of individuals followed since early childhood (N = 53, mean age 20.5 years). Analyses tested whether anxiety and/or cognitive control during adolescence moderated relations between BI and cortical thickness. Cognitive control was measured with the Eriksen Flanker Task. Initial analyses examined cortical thickness in regions of interest previously implicated in BI, anxiety disorders, and cognitive control: dorsal anterior cingulate (dACC), anterior insula (aI), and subgenual anterior cingulate (sgACC); and volumes of the amygdala and hippocampus. Exploratory analyses examined relations across the prefrontal cortex.Results: BI during early childhood related to thinner dACC in adulthood. Neither anxiety nor cognitive control moderated this relation. A stronger congruency effect on the Eriksen Flanker Task during adolescence independently related to thinner dACC in adulthood. Higher anxiety during adolescence related to thicker cortex in the right ventrolateral prefrontal cortex (VLPFC) in adulthood among those with low BI as children.Conclusion: Temperament in early childhood and the interaction between temperament and later anxiety relate to adult brain structure. These results are consistent with prior work associating BI and anxiety with functional brain variability in the dACC and VLPFC. [ABSTRACT FROM AUTHOR]