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Children who spend their early lives in institutions experience profound psychosocial deprivation that is associated with altered stress response system development. Here, we used data from a longitudinal randomized controlled trial of foster care for institutionally reared children to examine whether caregiving quality and stressful life events (SLEs) in early adolescence (age 12) influence patterns of hypothalamic–pituitary–adrenal (HPA) axis and sympathetic nervous system (SNS) reactivity. Controlling for the effect of institutional care, higher caregiving quality at age 12 was associated with heightened cortisol and SNS reactivity. However, moderation analysis revealed that the latter effect was only observed among never-institutionalized children, whereas ever-institutionalized children demonstrated a persistently blunted SNS response regardless of recent caregiving quality. Among institutionally reared children, SLEs interacted with prior random assignment to foster care, such that those placed in foster care early in development had a SNS response that approximated never-institutionalized children when SLEs at age 12 were low. In contrast, SNS reactivity was persistently blunted among those with prolonged deprivation, regardless of recent SLEs. Early-life deprivation is associated with persistent blunting of stress response systems, but normalization may be achievable if SLEs are limited following placement into enriched family-based care.
Early adversity has been shown to sensitize individuals to the effects of later stress and enhance risk of psychopathology. Using a longitudinal randomized trial of foster care as an alternative to institutional care, we extend the stress sensitization hypothesis to examine whether early institutional rearing sensitizes individuals to stressful events in adolescence engendering chronic low-grade inflammation. At baseline, institutionalized children in Romania (ages 6–31 months) were randomly assigned to foster care or to remain in usual care within institutions. A group of never-institutionalized children was recruited as an in-country comparison sample. At ages 12 and 16, participants reported stressful events. At age 16, Interleukin-6 (IL-6) and C-reactive protein (CRP) were derived from blood spots. Among children assigned to care as usual, more stressful events at age 12, but not age 16, were associated with higher IL-6. In the same group, stressful events at age 16 were associated with higher CRP, though these effects attenuated after adjusting for covariates. These associations were not observed in the foster care or never-institutionalized groups. The findings suggest that heightened inflammation following stress exposure is one pathway through which early neglect could compromise physical health. In contrast, early family care might buffer against these risks.
Children reared in institutions experience profound deprivation that is associated with both heightened levels of psychopathology and deficits in executive functioning (EF). It is unclear whether deficits in EF among institutionally-reared children serve as a vulnerability factor that increases risk for later psychopathology. It is also unclear whether this putative association between EF and psychopathology is transdiagnostic (i.e. cuts across domains of psychopathology), or specific to a given syndrome. Thus, we examined whether global deficits in EF mediate the association between severe childhood neglect and general v. specific psychopathology in adolescence.
The sample consisted of 188 children from the Bucharest Early Intervention Project, a longitudinal study examining the brain and behavioral development of children reared in Romanian institutions and a comparison group of never-institutionalized children. EF was assessed at age 8, 12, and 16 using a well-validated measure of neuropsychological functioning. Psychopathology was measured as general (P) and specific internalizing (INT) and externalizing (EXT) factors at age 12 and 16.
Institutionally-reared children had lower global EF and higher general psychopathology (P) at all ages compared to never-institutionalized children. Longitudinal path analysis revealed that the effect of institutionalization on P at age 16 operated indirectly through poorer EF from ages 8 to 12. No indirect effects involving EF were observed for INT or EXT at age 16.
We conclude that stable, global deficits in EF serve as a cognitive endophenotype that increases transdiagnostic vulnerability to psychopathology in adolescence among those who have experienced profound early neglect.
Individual differences in social-emotional functioning emerge early and have long-term implications for developmental adaptation and competency. Research is needed that specifies multiple early risk factors and outcomes simultaneously to demonstrate specificity. Using multigroup longitudinal path analysis in a sample of typically developing children (N = 541), we examined child temperament dimensions (surgency, negative affectivity, and regulation/effortful control) and maternal anxiety in infancy and age 2 as predictors of child externalizing, internalizing, dysregulation, and competence behaviors at age 3. Four primary patterns emerged. First, there was stability in temperament dimensions and maternal anxiety from infancy to age 3. Second, negative affectivity was implicated in internalizing problems and surgency in externalizing problems. Third, effortful control at age 2 was a potent mediator of maternal anxiety in infancy on age 3 outcomes. Fourth, there was suggestive evidence for transactional effects between maternal anxiety and child effortful control. Most pathways operated similarly for boys and girls, with some differences, particularly for surgency. These findings expand our understanding of the roles of specific temperamental domains and postnatal maternal anxiety in a range of social-emotional outcomes in the preschool period, and have implications for efforts to enhance the development of young children's social-emotional functioning and reduce risk for later psychopathology.
Schizophrenia affects 1% of the population. Clozapine is the only medication licensed for treatment-resistant schizophrenia and is intensively monitored to prevent harm from neutropenia. Clozapine is also associated with increased risk of pneumonia although the mechanism is poorly understood.
To investigate the potential association between clozapine and antibody deficiency.
Patients taking clozapine and patients who were clozapine-naive and receiving alternative antipsychotics were recruited and completed a lifestyle, medication and infection-burden questionnaire. Serum total immunoglobulins (immunoglobulin (Ig)G, IgA, IgM) and specific IgG antibodies to haemophilus influenzae type B, tetanus and IgG, IgA and IgM to pneumococcus were measured.
Immunoglobulins were all significantly reduced in the clozapine-treated group (n = 123) compared with the clozapine-naive group (n = 111). Odds ratios (ORs) for a reduction in clozapine:control immunoglobulin values below the fifth percentile were IgG, OR = 6.00 (95% CI 1.31–27.44); IgA, OR = 16.75 (95% CI 2.18–128.60); and IgM, OR = 3.26 (95% CI 1.75–6.08). These findings remained significant despite exclusion of other potential causes of hypogammaglobulinaemia. In addition, duration on clozapine was associated with decline in IgG. A higher proportion of the clozapine-treated group reported taking more than five courses of antibiotics in the preceding year (5.3% (n = 5) versus 1% (n = 1).
Clozapine use was associated with significantly reduced immunoglobulin levels and an increased proportion of patients using more than five antibiotic courses in a year. Antibody testing is not included in existing clozapine monitoring programmes but may represent a mechanistic explanation and modifiable risk factor for the increased rates of pneumonia and sepsis-related mortality previously reported in this vulnerable cohort.
Declaration of interest
S.J. has received support from CSL Behring, Shire, LFB, Biotest, Binding Site, Sanofi, GSK, UCB Pharma, Grifols, BPL SOBI, Weatherden, Zarodex and Octapharma for projects, advisory boards, meetings, studies, speaker and clinical trials.
Genetic variation in the oxytocin receptor gene (OXTR) is associated with several psychiatric conditions characterized by deficits in executive functioning (EF). A specific OXTR variant, rs2254298, has previously been associated with brain functioning in regions implicated in EF. Moreover, birth weight variation across the entire range is associated with individual differences in cortical structure and function that underlie EF. This is the first study to examine the main and interactive effect between rs2254298 and birth weight on EF in children. The sample consisted of 310 children from an ongoing longitudinal study. EF was measured at age 4.5 using observational tasks indexing working memory, cognitive flexibility, and inhibitory control. A family-based design that controlled for population admixture, stratification, and nongenomic confounds was employed. A significant genetic association between rs2254298 and EF was observed, with more copies of the major allele (G) associated with higher EF. There was also a significant interaction between rs2254298 and birth weight, such that more copies of the major allele in combination with higher birth weight predicted better EF. Findings suggest that OXTR may be associated with discrete neurocognitive abilities in childhood, and these effects may be modulated by intrauterine conditions related to fetal growth and development.
Scanning transmission electron microscope (STEM) through-focus imaging (TFI) has been used to determine the three-dimensional atomic structure of Bi segregation-induced brittle Cu grain boundaries (GBs). With TFI, it is possible to observe single Bi atom distributions along Cu  twist GBs using an aberration-corrected STEM operating at 200 kV. The depth resolution is ~5 nm. Specimens with GBs intentionally inclined with respect to the microscope’s optic axis were used to investigate Bi segregant atom distributions along and through the Cu GB. It was found that Bi atoms exist at most once per Cu unit cell along the GB, meaning that no continuous GB film is present. Therefore, the reduced fracture toughness of this particular Bi-doped Cu boundary would not be caused by fracture of Bi–Bi bonds.
By 18 months children demonstrate a range of social–cognitive skills that can be considered important precursors to more advanced forms of social understanding such as theory of mind. Although individual differences in social cognition have been linked to neurocognitive maturation, sociocultural models of development suggest that environmental influences operate in the development of children's social–cognitive outcomes. In the current study of 501 children and their mothers, we tested and found support for a model in which distal environmental risk, assessed when children were newborns, was indirectly associated with children's social–cognitive competency at 18 months through mothers' responsivity at 18 months. Part of this effect also operated through children's concomitant language skills, suggesting both a language-mediated and a language-independent mechanism of social–cognitive development. These findings are discussed with respect to the Vygotskian themes of internalization and semiotic mediation.
Natural disasters can result in a range of mental health outcomes among the affected population. Appropriate mental health interventions are required to promote recovery. In the aftermath of the 2009 bushfires in Victoria, Australia, a collaboration of trauma experts, the Australian and Victorian state governments and health professional associations developed an evidence-informed three-level framework outlining recommended levels of care. The framework was underpinned by an education and training agenda for mental health professionals. This framework has been successfully applied after further natural disasters in Australia. This paper outlines the steps included in each of the levels.
Multidrug-resistant (MDR) Acinetobacter baumannii and Pseudomonas aeruginosa have emerged as the causes of nosocomial infections in critically ill patients.
To characterize the incidence of these MDR bacteria over time in the military healthcare system, comparing isolates recovered from overseas combat casualties with isolates recovered from local military and civilian patients.
Retrospective electronic records review of culture and/or susceptibility testing results of patients admitted to a military level I trauma center in San Antonio, Texas, during the period from January 2001 through December 2008. Multidrug resistance was defined as the first isolated organism resistant to 3 or more classes of antimicrobial agents.
Over time, the percentage of MDR A. baumannii isolates increased from 4% to 55%, whereas the percentage of MDR P. aeruginosa isolates increased from 2% to 8%. Respiratory tract specimens had a higher percentage of MDR A. baumannii isolates (49%), compared with specimens obtained from blood (30%), wound sites (24%), or urine (19%). No difference in the percentages of MDR P. aeruginosa isolates was observed with regard to source of specimen. The percentage of MDR A. baumannii isolates recovered was higher among patients who had been deployed overseas (52%) than among local patients (20%). When isolates recovered from patients in the burn intensive care unit (53% of MDR A. baumannii isolates) were removed from analysis, the percentage of MDR A. baumannii isolates decreased from 38% to 30% while the percentage of MDR P. aeruginosa isolates remained unaffected.
The percentage of MDR A. baumannii isolates increased in this facility among combat casualties and among local patients, which indicates nosocomial transmission; however, there was no significant increase in the percentage of MDR P. aeruginosa isolates. Isolated changes in the MDR pathogens within a facility can occur. Possible interventions to limit the spread of these organisms could include implementing aggressive infection control practices, controlling antibiotic use, and using active culture surveillance.
Applications of nanoscience in the non-traditional classroom have successfully exposed students to various methods of research with applications to micro- and nano-electronics. Activities obtained from the NanoSense website associated with current global energy and water concerns are solid examples. In this regard, all 36 students in the 2008-2009 Science Research Program (SRP) prepared and delivered individual and group lesson plans in addition to their authentic, year-long research projects. Two out of 36 students selected nanoscience based projects in preparation for science fair competition in 2009. Additionally, preliminary research was conducted while participating in the Center for Research on Interface Structures and Phenomena (CRISP) Research Experience for Teachers (RET) Program in summer 2008 which supported the idea of developing a photolithography kit. This kit is intended to introduce high school students to the fundamentals of photolithography. In this paper, the design, implementation and feasibility of this kit in the high school classroom is described as well as details involving individual and group nanoscience based projects. Supporting educational models include self-regulated learning (SRL) concepts; situated cognition; social constructivism; Renzulli's (1977) enrichment triad and Types I – III inquiry enrichment activities.
Obtaining estimates of pesticide productivity is an economic response to the growing public concern about the steady increase of pesticide use in the United States. This type of research indicates the cost of limiting pesticide use in terms of foregone output. Previous empirical studies give a “snap-shot”, or “average”, look at pesticide productivity. This research effort employs a random coefficient model to determine the trend of the marginal value product of pesticides in agriculture in the United States. Results show a distinct downward trend in two states, Iowa and Texas. California, however, shows no evidence of a downward trend.
In our continuing efforts towards the design of nonlinear (NLO) optical chromophore containing polypeptides we present an integrated computational approach, in which the design of biomolecular materials with defined secondary and tertiary structures is investigated by means of novel predictive tools, while the effects of the nonlinear optical chromophores are studied with molecular dynamics simulations. A neural network that was trained to predict the spatial proximity of Cα atoms that are less than a given threshold apart, is applied. The double-iterated Kalman filter (DIKF) technique is then employed with a constraints set that includes these pairwise atomic distances, and the distances and angles that define the structure as it is known from the protein's sequence. The results for test cases, particularly Crambin and genetically engineered Eglin-C, demonstrate that this integrated approach is useful for structure prediction at an intermediate resolution. Defined structural motifs of NLO chromophore containing polypeptides are investigated by using molecular dynamics techniques, particularly for the design of coil coiled amphiphatic biopolymers.
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