Detection of EGFR mutations in non-small cell lung cancer by droplet digital PCR.

Activating mutations in EGFR predict benefit from tyrosine kinase inhibitor therapy for patients with advanced non-small cell lung cancer. Directing patients to appropriate therapy depends on accurate and timely EGFR assessment in the molecular pathology laboratory. This article describes the analytical design, performance characteristics, and clinical implementation of an assay for the rapid detection of EGFR L858R and exon 19 deletion mutations.

Role of Risk Taking and Inhibitory Control in Alcohol Use Among Maltreated Adolescents and Nonmaltreated Adolescents.

Exposure to childhood maltreatment is a significant risk factor for the development and persistence of problematic alcohol use. The present study examined the role of risk taking and inhibitory control, key cognitive processes believed to govern behavioral regulation, as mechanisms that underlie the association between childhood maltreatment and the early stages of alcohol use. A sample of 129 maltreated adolescents and 102 socioeconomic status-matched, nonmaltreated adolescents and their parents completed three annual assessments, including computer-administered tasks and adolescent- and parent-report questionnaires, across ages 12-13 through 14-15 years.

Behavioral and electrophysiological indices of inhibitory control in maltreated adolescents and nonmaltreated adolescents.

Early adverse experiences are believed to have a profound effect on inhibitory control and the underlying neural regions. In the current study, behavioral and event-related potential (ERP) data were collected during a go/no-go task from adolescents who were involved with the child welfare system due to child maltreatment ( = 129) and low-income, nonmaltreated adolescents ( = 102). The nonmaltreated adolescents were more accurate than the maltreated adolescents on the go/no-go task, particularly on the no-go trials.

Effects of a school readiness intervention on electrophysiological indices of external response monitoring in children in foster care.

This study examined the impact of a school readiness intervention on external response monitoring in children in foster care. Behavioral and event-related potential (ERP) data were collected during a flanker task from children who received the Kids In Transition to School (KITS) Program (n = 26) and children who received services as usual (n = 19) before and after the intervention. While there were no significant group differences on the behavioral data, the ERP data for the two groups of children significantly differed.

Exploring the Psychometric Properties of the Parent Daily Report - Toddler Version (PDR-T).

The present study examined the psychometric properties of a brief parent-report daily checklist of toddler behavior (Parent Daily Report - Toddler Version; PDR-T). Data were collected from three groups of 18-36 month-olds who were followed longitudinally for approximately 1 year: 1) internationally adopted children ( = 156), 2) children placed in foster care due to child maltreatment ( = 79), and 3) community comparison children raised by their biological families ( = 80). An exploratory factor analysis of this measure resulted in three factors, measuring aggressive/noncompliant, positive, and distress behaviors.

General Cognitive Ability as an Early Indicator of Problem Behavior Among Toddlers in Foster Care.

Objective: Children who have experienced maltreatment and subsequent placement in foster care are at increased risk of problem behavior. Increased knowledge of the development of problem behavior in this population, particularly during toddlerhood, can greatly inform preventive intervention efforts. This study examined variability in problem behavior among toddlers entering new foster care placements and identified related child and parenting characteristics.

Effects of a school readiness intervention on hypothalamus-pituitary-adrenal axis functioning and school adjustment for children in foster care.

Maltreated children in foster care are at high risk for dysregulated hypothalamus-pituitary-adrenal (HPA) axis functioning and educational difficulties. The present study examined the effects of a short-term school readiness intervention on HPA axis functioning in response to the start of kindergarten, a critical transition marking entry to formal schooling, and whether altered HPA axis functioning influenced children's school adjustment. Compared to a foster care comparison group, children in the intervention group showed a steeper diurnal cortisol slope on the first day of school, a pattern previously observed among nonmaltreated children.

Improving kindergarten readiness in children with developmental disabilities: Changes in neural correlates of response monitoring.

Among children diagnosed with developmental delays, difficulties in self-regulation are prominent and have been linked to school readiness problems. The current study sought to examine the impact of the Kids in Transition to School (KITS) school readiness intervention program on self-regulation, with a specific focus on response monitoring skills, among children with developmental delays. Children (n = 20 in the KITS group and n = 21 in a services as usual group) were administered a flanker task during which event-related potential data were collected to examine group differences in response monitoring.

Detection of Mismatch Repair Deficiency and Microsatellite Instability in Colorectal Adenocarcinoma by Targeted Next-Generation Sequencing.

Mismatch repair protein deficiency (MMR-D) and high microsatellite instability (MSI-H) are features of Lynch syndrome-associated colorectal carcinomas and have implications in clinical management. We evaluate the ability of a targeted next-generation sequencing panel to detect MMR-D and MSI-H based on mutational phenotype. Using a criterion of >40 total mutations per megabase or >5 single-base insertion or deletion mutations in repeats per megabase, sequencing achieves 92% sensitivity and 100% specificity for MMR-D by immunohistochemistry in a training cohort of 149 colorectal carcinomas and 91% sensitivity and 98% specificity for MMR-D in a validation cohort of 94 additional colorectal carcinomas.

The Clinical Implications of Inconsistently Methylated Results from Glioblastoma MGMT Testing by Replicate Methylation-Specific PCR.

The methylation status of the promoter of the O-methylguanine DNA methyltransferase gene (MGMT) is an established prognostic and predictive biomarker of glioblastoma (GBM). At the Center for Advanced Molecular Diagnostics, MGMT testing is performed by methylation-specific PCR with multiple replicates, leading to three types of reportable results: methylated, unmethylated, and inconsistently methylated. An inconsistently methylated result is reported when a methylated peak is seen in some but not all of the PCR replicates from a single DNA sample.

Preliminary evidence of the impact of early childhood maltreatment and a preventive intervention on neural patterns of response inhibition in early adolescence.

Maltreated youths in foster care often experience negative developmental and psychological outcomes, which have been linked with poor response inhibition. Recent evidence suggests that childhood maltreatment is also associated with alterations in the neural circuitry underlying response inhibition. However, a burgeoning line of research has begun to explore the mitigating effects of preventive interventions on neural functioning.

Income, neural executive processes, and preschool children's executive control.

This study aimed to specify the neural mechanisms underlying the link between low household income and diminished executive control in the preschool period. Specifically, we examined whether individual differences in the neural processes associated with executive attention and inhibitory control accounted for income differences observed in performance on a neuropsychological battery of executive control tasks. The study utilized a sample of preschool-aged children (N = 118) whose families represented the full range of income, with 32% of families at/near poverty, 32% lower income, and 36% middle to upper income.

Impulsivity and the association between the feedback-related negativity and performance on an inhibitory control task in young at-risk children.

Identifying neurocognitive processes associated with effective inhibitory control is particularly relevant for individuals at high risk for disruptive behaviors, such as maltreated children. Performance feedback processing during a flanker task was investigated in maltreated preschool-aged children (N = 67) via an event-related potential component, the feedback-related negativity (FRN). The functionality of the FRN in children with high impulsivity was of interest, as impulsivity was associated with an exaggerated FRN in previous research.

HPA stability for children in foster care: mental health implications and moderation by early intervention.

Research on stress-sensitive biological systems has typically focused on activation at one time, yet recent theories emphasize dynamic, context-specific adaptation. This study tested hypothesized calibration of one such system by examining both mean levels and longitudinal stability of daily cortisol--reflecting hypothalamic-pituitary-adrenal axis activation--in children exposed to high-risk versus lower-risk caregiving contexts. Context-specific effects of longitudinal cortisol profiles were addressed via relations with child psychiatric symptoms.

Child diurnal cortisol rhythms, parenting quality, and externalizing behaviors in preadolescence.

This study examined a neurobiologically informed model of the emergence of child externalizing behaviors in an ethnically diverse community sample of 232 9-12 year old children. Replicating extensive prior research, our analyses revealed that parents' inconsistent discipline and poor quality monitoring were predictive of child externalizing behavior. In addition, poor parental monitoring, but not inconsistent discipline, was associated with children having a significantly flatter morning-to-evening cortisol slope, which was in turn, related to higher levels of externalizing behaviors.

Patterns of brain activation in foster children and nonmaltreated children during an inhibitory control task.

Children in foster care have often encountered a range of adverse experiences, including neglectful and/or abusive care and multiple caregiver transitions. Prior research findings suggest that such experiences negatively affect inhibitory control and the underlying neural circuitry. In the current study, event-related functional magnetic resonance imaging was employed during a go/no go task that assesses inhibitory control to compare the behavioral performance and brain activation of foster children and nonmaltreated children.

Immediate Effects of a School Readiness Intervention for Children in Foster Care.

Research Findings: School readiness is a strong predictor of adjustment in elementary school and beyond. Children in foster care are at particular risk for academic and social difficulties in school. Limitations in self-regulatory skills and caregiver involvement among these children might contribute to a lack of school readiness.

Pulmonary large cell carcinoma lacking squamous differentiation is clinicopathologically indistinguishable from solid-subtype adenocarcinoma.

Context: Pulmonary large cell carcinoma (LCC) includes tumors not readily diagnosed as adenocarcinoma (ADC) or squamous cell carcinoma on morphologic grounds, without regard to immunophenotype, according to the World Health Organization (WHO). This ambiguous designation may cause confusion over selection of mutation testing and directed therapies. Several groups have proposed the use of immunohistochemistry (IHC) to recategorize LCC as ADC or squamous cell carcinoma; however, it remains unclear if strictly defined LCCs are a clinicopathologically distinct lung tumor subset.

Early adverse care, stress neurobiology, and prevention science: lessons learned.

There is growing evidence that some of the difficulties observed among children who have experienced early adverse care (e.g., children internationally adopted from institutional care and maltreated children in foster care) involve experience-induced alterations in stress-responsive neurobiological systems, including the hypothalamic-pituitary-adrenocortical (HPA) system.

Cumulative Effects of Prenatal Substance Exposure and Early Adversity on Foster Children's HPA Axis Reactivity During a Psychosocial Stressor.

Dysregulated hypothalamic-pituitary-adrenocortical (HPA) axis stress response has been reported among individuals with prenatal substance exposure and those with early adversity. However, few researchers have examined the combined effects of these risk factors. Patterns of HPA reactivity among maltreated foster children with and without prenatal substance exposure (N = 53; ages 9-12 years) were examined using the Trier Social Stress Test for Children.

Racial and ethnic differences in diurnal cortisol rhythms in preadolescents: the role of parental psychosocial risk and monitoring.

Racial/ethnic minorities experience persistent health disparities due in part to their exposure to chronic SES and psychosocial risk. The hypothalamic-pituitary-adrenal axis and its hormonal end product, cortisol, are believed to mediate the associations between chronic stress and poor health. In this study, racial/ethnic differences in diurnal salivary cortisol rhythms in 179 preadolescent youths and the contributing roles of SES risk, psychosocial risk, perceived discrimination, harsh parenting, and parental monitoring were examined.

Growth delay as an index of allostatic load in young children: predictions to disinhibited social approach and diurnal cortisol activity.

The goal of this study was to examine whether growth delay can serve as an index of allostatic load during early development, as it is well known that the activity of stress-mediating systems inhibits growth. The participants were children adopted internationally from institutional care (n = 36), children adopted internationally from foster care (n = 26), and nonadopted children (n = 35). For the adopted children, height for age and weight for height were assessed at adoption; for all children, disinhibited social approach (DSA; termed elsewhere as "indiscriminate friendliness") and diurnal cortisol were assessed at 6-8 years (M = 6.

Early elementary school adjustment of maltreated children in foster care: the roles of inhibitory control and caregiver involvement.

In this study, 85 maltreated foster children and 56 non-maltreated community children (M age=3-6 years) were assessed across kindergarten and first grade to examine the hypothesis that inhibitory control and caregiver involvement mediate associations between a history of maltreatment and foster placement and early school adjustment. Specifically, academic and social-emotional competence were evaluated. The maltreated foster children performed more poorly in academic and social-emotional competence.