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The Interplay of Genes and Environment across Multiple Studies (IGEMS) is a consortium of 18 twin studies from 5 different countries (Sweden, Denmark, Finland, United States, and Australia) established to explore the nature of gene–environment (GE) interplay in functioning across the adult lifespan. Fifteen of the studies are longitudinal, with follow-up as long as 59 years after baseline. The combined data from over 76,000 participants aged 14–103 at intake (including over 10,000 monozygotic and over 17,000 dizygotic twin pairs) support two primary research emphases: (1) investigation of models of GE interplay of early life adversity, and social factors at micro and macro environmental levels and with diverse outcomes, including mortality, physical functioning and psychological functioning; and (2) improved understanding of risk and protective factors for dementia by incorporating unmeasured and measured genetic factors with a wide range of exposures measured in young adulthood, midlife and later life.
Objectives: We conducted joint analyses from five randomized clinical trials (RCTs) of online family problem-solving therapy (OFPST) for children with traumatic brain injury (TBI) to identify child and parent outcomes most sensitive to OFPST and trajectories of recovery over time. Methods: We examined data from 359 children with complicated mild to severe TBI, aged 5–18, randomized to OFPST or a control condition. Using profile analyses, we examined group differences on parent-reported child (internalizing and externalizing behavior problems, executive function behaviors, social competence) and family outcomes (parental depression, psychological distress, family functioning, parent–child conflict). Results: We found a main effect for measure for both child and family outcomes [F(3, 731) = 7.35, p < .001; F(3, 532) = 4.79, p = .003, respectively], reflecting differing degrees of improvement across measures for both groups. Significant group-by-time interactions indicated that children and families in the OFPST group had fewer problems than controls at both 6 and 18 months post baseline [t(731) = −5.15, p < .001, and t(731) = −3.90, p = .002, respectively, for child outcomes; t(532) = −4.81, p < .001, and t(532) = −3.80, p < .001, respectively, for family outcomes]. Conclusions: The results suggest limited differences in the measures’ responsiveness to treatment while highlighting OFPST’s utility in improving both child behavior problems and parent/family functioning. Group differences were greatest at treatment completion and after extended time post treatment.
The aggregation of neurocognitive deficits among the non-psychotic first-degree relatives of adult- and childhood-onset schizophrenia patients suggests that there may be a common etiology for these deficits in childhood- and adult-onset illness. However, there is considerable heterogeneity in the presentation of neurobiological abnormalities, and whether there are differences in the extent of familial transmission for specific domains of cognitive function has not been systematically addressed.
We employed variance components analysis, as implemented in SOLAR-Eclipse, to evaluate the evidence of familial transmission for empirically derived composite scores representing attention, working memory, verbal learning, verbal retention, and memory for faces. We contrast estimates for adult- and childhood-onset schizophrenia families and matched community control pedigrees, and compare our findings to previous reports based on analogous neurocognitive assessments.
We observed varying degrees of familial transmission; attention and working memory yielded comparable, significant estimates for adult-onset and community control pedigrees; verbal learning was significant for childhood-onset and community control pedigrees; and facial memory demonstrated significant familial transmission only for childhood-onset schizophrenia. Model-fitting analyses indicated significant differences in familiality between adult- and childhood-onset schizophrenia for attention, working memory, and verbal learning.
By comprehensively assessing a wide range of neurocognitive domains in adult- and childhood-onset schizophrenia families, we provide additional support for specific neurocognitive domains as schizophrenia endophenotypes. Whereas comparable estimates of familial transmission for certain dimensions of cognitive functioning support a shared etiology of adult- and childhood-onset neurocognitive function, observed differences may be taken as preliminary evidence of partially divergent multifactorial architectures.
Clinical Enterobacteriacae isolates with a colistin minimum inhibitory concentration (MIC) ≥4 mg/L from a United States hospital were screened for the mcr-1 gene using real-time polymerase chain reaction (RT-PCR) and confirmed by whole-genome sequencing. Four colistin-resistant Escherichia coli isolates contained mcr-1. Two isolates belonged to the same sequence type (ST-632). All subjects had prior international travel and antimicrobial exposure.
Crystallization is an extremely important process with extensive industrial applications including, but not limited to, the manufacture of electronics, explosives, fine chemicals, and pharmaceuticals. As such, controlling both crystal shape and crystal structure is vital for the production of high-quality products with desirable properties. However, the processes that govern crystallization, crystal growth, and crystal nucleation are not well understood at present. This is due in part to the limitations of experimental techniques in studying such processes because of the small number of molecules, often tens or hundreds, involved. Furthermore, experimental strategies for identifying and analyzing crystal structures (which may have serious implications in terms of intellectual property rights) and controlling crystal shape are not always successful in yielding the optimal product and often can be costly and time consuming.
Speleothem organic matter can be a powerful tracer for past environmental conditions and karst processes. Carbon isotope measurements (δ13C and 14C) in particular can provide crucial information on the provenance and age of speleothem organic matter, but are challenging due to low concentrations of organic matter in stalagmites. Here, we present a method development study on extraction and isotopic characterization of speleothem organic matter using a rapid procedure with low laboratory contamination risk. An extensive blank assessment allowed us to quantify possible sources of contamination through the entire method. Although blank contamination is consistently low (1.7 ± 0.34 – 4.3 ± 0.86 μg C for the entire procedure), incomplete sample decarbonation poses a still unresolved problem of the method, but can be detected when considering both δ13C and 14C values. We test the method on five stalagmites, showing reproducible results on samples as small as 7 μg C for δ13C and 20 μg C for 14C. Furthermore, we find consistently lower non-purgeable organic carbon (NPOC) 14C values compared to the carbonate 14C over the bomb spike interval in two stalagmites from Yok Balum Cave, Belize, suggesting overprint of a pre-aged or even fossil source of carbon on the organic fraction incorporated by these stalagmites.
Objectives: Examine the mediating effects of anxiety and depressive symptoms on the relationship between psychological resilience and post-concussive symptoms (PCS) in children with poor recovery following concussion. Participants and Methods: Adolescents (N=93), ages 13 to 18 years, were assessed at a neuropsychology screening clinic at a children’s hospital. They sustained concussions more than 1 month before the clinic visit (median time since injury=5.1 months; range=42–473 days) and were seen on the basis of poor recovery (i.e., presence of persistent PCS and complaints of cognitive problems). Self-reported psychological resilience was measured using the 10-item version of the Connor-Davidson Resilience Scale; self- and parent-reported anxiety and depressive symptoms were measured using the Behaviour Assessment System for Children – Second Edition; and self- and parent-reported PCS were measured using the Post-Concussion Symptom Inventory. All variables were measured concurrently. Regression-based mediation analyses were conducted to examine anxiety and depressive symptoms as mediators of the relationship between psychological resilience and PCS. Results: Psychological resilience significantly predicted self-reported PCS. Self-reported anxiety and depressive symptoms significantly mediated the relationship between resilience and self-reported PCS, and parent-reported child depressive symptoms significantly mediated the relationship between resilience and self- and parent-reported PCS. Conclusions: Psychological resilience plays an important role in recovery from concussion, and this relationship may be mediated by anxiety and depressive symptoms. These results help shed light on the mechanisms of the role of psychological resilience in predicting PCS in children with prolonged symptom recovery. (JINS, 2019, 25, 346–354)
Objective: Concussion in children and adolescents is a prevalent problem with implications for subsequent physical, cognitive, behavioral, and psychological functioning, as well as quality of life. While these consequences warrant attention, most concussed children recover well. This study aimed to determine what pre-injury, demographic, and injury-related factors are associated with optimal outcome (“wellness”) after pediatric concussion. Method: A total of 311 children 6–18 years of age with concussion participated in a longitudinal, prospective cohort study. Pre-morbid conditions and acute injury variables, including post-concussive symptoms (PCS) and cognitive screening (Standardized Assessment of Concussion, SAC), were collected in the emergency department, and a neuropsychological assessment was performed at 4 and 12 weeks post-injury. Wellness, defined by the absence of PCS and cognitive inefficiency and the presence of good quality of life, was the main outcome. Stepwise logistic regression was performed using 19 predictor variables. Results: 41.5% and 52.2% of participants were classified as being well at 4 and 12 weeks post-injury, respectively. The final model indicated that children who were younger, who sustained sports/recreational injuries (vs. other types), who did not have a history of developmental problems, and who had better acute working memory (SAC concentration score) were significantly more likely to be well. Conclusions: Determining the variables associated with wellness after pediatric concussion has the potential to clarify which children are likely to show optimal recovery. Future work focusing on wellness and concussion should include appropriate control groups and document more extensively pre-injury and injury-related factors that could additionally contribute to wellness. (JINS, 2019, 25, 375–389)
OBJECTIVES/SPECIFIC AIMS: Intensive lifestyle change (e.g., the Diabetes Prevention Program) and metformin reduce type 2 diabetes risk among patients with prediabetes. However, real-world uptake remains low. Shared decision-making (SDM) may increase awareness and help patients select and follow through with informed options for diabetes prevention that are aligned with their preferences.The objective was to test the effectiveness of a prediabetes SDM intervention. METHODS/STUDY POPULATION: This was a cluster-randomized controlled trial in 20 primary care clinics within a large regional health system. Participants were overweight/obese adults with prediabetes (BMI>24 kg/m2 and HbA1c 5.7-6.4%) were enrolled from 10 SDM intervention clinics. Propensity score matching was used to identify control patients from 10 usual care clinics.Intervention clinic patients were invited to participate in a face-to-face SDM visit with a pharmacist who used a decision aid (DA) to describe prediabetes and four possible options for diabetes prevention; DPP, DPP +/− metformin, metformin only, or usual care. RESULTS/ANTICIPATED RESULTS: Uptake of DPP and/or metformin was higher among SDM participants (n=351) than controls receiving usual care (n = 1,028; 38% vs. 2%, p<.001). At 12-months follow-up, adjusted weight loss (lbs.) was greater among SDM participants than controls (−5.3 vs. −0.2, p < .001). DISCUSSION/SIGNIFICANCE OF IMPACT: A prediabetes SDM intervention led by pharmacists increased patient engagement in evidence-based options for diabetes prevention and was associated with significantly greater uptake of DPP and/or metformin at 4-months and weight loss at 12-months. Prediabetes SDM may be a promising approach to enhance prevention efforts among patients at increased risk.
This study evaluated in a rigorous 18-month randomized controlled trial the efficacy of an enhanced vocational intervention for helping individuals with a recent first schizophrenia episode to return to and remain in competitive work or regular schooling.
Individual Placement and Support (IPS) was adapted to meet the goals of individuals whose goals might involve either employment or schooling. IPS was combined with a Workplace Fundamentals Module (WFM) for an enhanced, outpatient, vocational intervention. Random assignment to the enhanced integrated rehabilitation program (N = 46) was contrasted with equally intensive clinical treatment at UCLA, including social skills training groups, and conventional vocational rehabilitation by state agencies (N = 23). All patients were provided case management and psychiatric services by the same clinical team and received oral atypical antipsychotic medication.
The IPS–WFM combination led to 83% of patients participating in competitive employment or school in the first 6 months of intensive treatment, compared with 41% in the comparison group (p < 0.005). During the subsequent year, IPS–WFM continued to yield higher rates of schooling/employment (92% v. 60%, p < 0.03). Cumulative number of weeks of schooling and/or employment was also substantially greater with the IPS–WFM intervention (45 v. 26 weeks, p < 0.004).
The results clearly support the efficacy of an enhanced intervention focused on recovery of participation in normative work and school settings in the initial phase of schizophrenia, suggesting potential for prevention of disability.
Inappropriate antibiotic use is associated with increased antimicrobial resistance and adverse events that can lead to further downstream patient harm. Preventative strategies must be employed to improve antibiotic use while reducing avoidable harm. We use the term “antibiotic never events” to globally recognize and define the most inappropriate antibiotic use.
The detection and monitoring of meltwater within firn presents a significant monitoring challenge. We explore the potential of small wireless sensors (ETracer+, ET+) to measure temperature, pressure, electrical conductivity and thus the presence or absence of meltwater within firn, through tests in the dry snow zone at the East Greenland Ice Core Project site. The tested sensor platforms are small, robust and low cost, and communicate data via a VHF radio link to surface receivers. The sensors were deployed in low-temperature firn at the centre and shear margins of an ice stream for 4 weeks, and a ‘bucket experiment’ was used to test the detection of water within otherwise dry firn. The tests showed the ET+ could log subsurface temperatures and transmit the recorded data through up to 150 m dry firn. Two VHF receivers were tested: an autonomous phase-sensitive radio-echo sounder (ApRES) and a WinRadio. The ApRES can combine high-resolution imaging of the firn layers (by radio-echo sounding) with in situ measurements from the sensors, to build up a high spatial and temporal resolution picture of the subsurface. These results indicate that wireless sensors have great potential for long-term monitoring of firn processes.
Psychopathy is a personality disorder associated with severe emotional and interpersonal consequences and persistent antisocial behavior. Neurobiological models of psychopathy emphasize impairments in emotional processing, attention, and integration of information across large-scale neural networks in the brain. One of the largest integrative hubs in the brain is the corpus callosum (CC) – a large white matter structure that connects the two cerebral hemispheres.
The current study examines CC volume, measured via Freesurfer parcellation, in a large sample (n = 495) of incarcerated men who were assessed for psychopathic traits using the Hare Psychopathy Checklist-Revised (PCL-R).
Psychopathy was associated with reduced volume across all five sub-regions of the CC. These relationships were primarily driven by the affective/interpersonal elements of psychopathy (PCL-R Factor 1), as no significant associations were found between the CC and the lifestyle/antisocial traits of psychopathy. The observed effects were not attributable to differences in substance use severity, age, IQ, or total brain volume.
These findings align with suggestions that core psychopathic traits may be fostered by reduced integrative capacity across large-scale networks in the brain.
Objectives: To evaluate the relationship of psychological resilience to persistent post-concussive symptoms (PCS) in children with a history of single or multiple concussions, as well as orthopedic injury (OI). Methods: Participants (N=75) were children, ages 8–18 years, who sustained a single concussion (n=24), multiple concussions (n=25), or an OI (n=26), recruited from a tertiary care children’s hospital. All participants sustained injuries at least 6 months before recruitment, with an average time since injury of 32.9 months. Self-reported psychological resilience was measured using the Connor-Davidson Resilience Scale, and both self- and parent-reported PCS were measured using the Post-Concussion Symptom Inventory. Hierarchical regression analyses examined psychological resilience as a predictor of PCS, both as a main effect and as a moderator of group differences. Results: Multiple concussions and low psychological resilience were both significant predictors of persistent PCS. Resilience was not a significant moderator of group differences in PCS. Conclusions: Sustaining multiple concussions may increase a child’s risk of persistent PCS; however, high psychological resilience may serve as a protective factor, regardless of the number or type of injuries sustained. These findings provide support for developing and testing interventions aimed at increasing psychological resilience as a potential means of improving outcomes for children suffering from persistent PCS after concussion. (JINS, 2018, 24, 759–768)