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Background: Beyond the core symptoms of autism spectrum disorder (ASD), associated symptoms of anxiety can cause substantial impairment for individuals affected by ASD and those who care for them., Methods: We utilized a potentiated startle paradigm with a puff of air to the neck as the unconditioned stimulus in order to investigate differences between response to cued fear and contextual anxiety among cognitively able adolescents diagnosed with ASD and an age- and IQ-matched typically developing group., Results: In a threat-modulated startle paradigm, response patterns to neutral, predictable, and unpredictable conditions were comparable across typically developing and ASD youth in terms of startle response magnitude and latency. However, the ASD group showed significantly greater absolute startle responsivity at baseline and throughout the experiment, suggesting possibly enhanced general sensitivity to threatening contexts. The ASD group, but not the control group, demonstrated moderate to strong negative correlations between psychophysiological response to unpredictable threats (uncertainty) and questionnaire measures of generalized anxiety, intolerance of uncertainty, and repetitive behavior., Conclusions: Our data suggest enhanced general reactivity among the ASD group, possibly reflecting greater sensitivity to the threatening context of the startle paradigm. Associations with the response to uncertainty may help explain shared neurobehavioral mechanisms in ASD and anxiety. This task can provide useful targets for future neuroimaging and genetics studies as well as specific avenues for intervention. We emphasize the importance of further basic and clinical research into links among these important constructs.

Background: Despite recognition of the benefits associated with well-controlled diabetes and hypertension, control remains suboptimal. Effective interventions for these conditions have been studied within academic settings, but interventions targeting both conditions have rarely been tested in community settings. We describe the design and baseline results of a trial evaluating a behavioral intervention among community patients with poorly-controlled diabetes and comorbid hypertension., Methods: Tailored Case Management for Diabetes and Hypertension (TEACH-DM) is a 24-month randomized, controlled trial evaluating a telephone-delivered behavioral intervention for diabetes and hypertension versus attention control. The study recruited from nine community practices. The nurse-administered intervention targets 3 areas: 1) cultivation of healthful behaviors for diabetes and hypertension control; 2) provision of fundamentals to support attainment of healthful behaviors; and 3) identification and correction of patient-specific barriers to adopting healthful behaviors. Hemoglobin A1c and blood pressure measured at 6, 12, and 24 months are co-primary outcomes. Secondary outcomes include self-efficacy, self-reported medication adherence, exercise, and cost-effectiveness., Results: Of 377 randomized patients, 193 were allocated to the intervention and 184 to attention control. The cohort is balanced in terms of gender, race, education level, and income. The cohort's mean baseline hemoglobin A1c and blood pressure are above goal, and mean baseline body mass index falls in the obese range. Baseline self-reported non-adherence is high for diabetes and hypertension medications. Trial results are pending., Conclusions: If effective, the TEACH-DM intervention's telephone-based delivery strategy and nurse administration make it well-suited for rapid implementation and broad dissemination in community settings., (© 2013.)

Background: Cardiovascular disease (CVD) and diabetes account for one-third of the mortality difference between African American and white patients. We evaluated the effect of a CVD risk reduction intervention in African Americans with diabetes., Methods: We randomized 359 African Americans with type 2 diabetes to receive usual care or a nurse telephone intervention. The 12-month intervention provided monthly self-management support and quarterly medication management facilitation. Coprimary outcomes were changes in systolic blood pressure (SBP), hemoglobin A1c (HbA1c), and low-density lipoprotein cholesterol (LDL-C) over 12 months. We estimated between-intervention group differences over time using linear mixed-effects models. The secondary outcome was self-reported medication adherence., Results: The sample was 72% female; 49% had low health literacy, and 37% had annual income <$10,000. Model-based estimates for mean baseline SBP, HbA1c, and LDL-C were 136.8 mm Hg (95% CI 135.0-138.6), 8.0% (95% CI 7.8-8.2), and 99.1 mg/dL (95% CI 94.7-103.5), respectively. Intervention patients received 9.9 (SD 3.0) intervention calls on average. Primary providers replied to 76% of nurse medication management facilitation contacts, 18% of these resulted in medication changes. There were no between-group differences over time for SBP (P = .11), HbA1c (P = .66), or LDL-C (P = .79). Intervention patients were more likely than those receiving usual care to report improved medication adherence (odds ratio 4.4, 95% CI 1.8-10.6, P = .0008), but adherent patients did not exhibit relative improvement in primary outcomes., Conclusions: This intervention improved self-reported medication adherence but not CVD risk factor control among African Americans with diabetes. Further research is needed to determine how to maximally impact CVD risk factors in African American patients., (Copyright © 2013 Mosby, Inc. All rights reserved.)

Objective: Group medical clinics (GMC) combine medication management and self-management training, and may improve diabetes outcomes. It remains unclear which patients benefit most from GMC. This secondary analysis examined the impact of baseline insulin regimen on GMC response., Research Design and Methods: We analyzed a trial of 239 veterans with type 2 diabetes randomized to GMC or usual care (UC). We categorized baseline insulin regimen as the following: no insulin; basal insulin only; or complex insulin (basal-prandial or mixed regimens). Using linear mixed models adjusted for clustering within GMC, we evaluated the differential impact of GMC relative to UC on hemoglobin A1c (HbA1c) and self-efficacy among patients on different baseline insulin regimens., Results: From linear mixed models, the effect of GMC on HbA1c differed by baseline insulin regimen versus UC (P = 0.05); there was no differential effect on self-efficacy (P = 0.29). Among those using complex insulin regimens at baseline, GMC reduced HbA1c by study end compared with UC (-1.0%; 95% CI -1.8 to -0.2; P = 0.01). We found no such HbA1c difference between GMC and UC patients using no insulin (P = 0.65) or basal insulin only (P = 0.71). There were no clinically significant differences in hypoglycemia by baseline insulin regimen and intervention group., Conclusions: We found that compared with UC, GMC lowered HbA1c specifically among patients using complex insulin regimens at study baseline, which may relate to this group's demanding medication and self-management requirements. Implementing GMC among patients using complex insulin regimens may maximize this care delivery strategy's potential.

Background: The BRAF(V600E) mutation is present in 62% of radioactive iodine-resistant thyroid tumors and is associated with downregulation of the sodium-iodide symporter (NIS) and thyroid stimulating hormone receptor (TSHr). We sought to evaluate the combined effect of BRAF inhibition and TSH supplementation on (131)I uptake of BRAF(V600E)-mutant human thyroid cancer cells., Materials and Methods: WRO cells (a BRAF(V600E)-mutant follicular-derived papillary thyroid carcinoma cell line) were transfected with small interfering RNA targeting BRAF for 72 h in a physiological TSH environment. NIS and TSHr expression were then evaluated at three levels: gene expression, protein levels, and (131)I uptake. These three main outcomes were then reassessed in TSH-depleted media and media supplemented with supratherapeutic concentrations of TSH., Results: NIS gene expression increased 5.5-fold 36 h after transfection (P = 0.01), and TSHr gene expression increased 2.8-fold at 24 h (P = 0.02). NIS and TSHr protein levels were similarly increased 48 and 24 h after transfection, respectively. Seventy-two hours after BRAF inhibition, (131)I uptake was unchanged in TSH-depleted media, increased by 7.5-fold (P < 0.01) in physiological TSH media, and increased by 9.1-fold (P < 0.01) in supratherapeutic TSH media., Conclusions: The combined strategy of BRAF inhibition and TSH supplementation results in greater (131)I uptake than when either technique is used alone. This represents a simple and feasible approach that may improve outcomes in patients with radioactive iodine-resistant thyroid carcinomas for which current treatment algorithms are ineffective., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: Preoperative B-type Raf kinase Val600Glu mutation, or BRAF(V600E), analysis has been proposed as a tool to guide initial surgery for indeterminate thyroid nodules. This study sought to determine if cytologic markers of malignancy are associated with the BRAF(V600E) mutation and if preoperative BRAF(V600E) testing would alter the initial management of patients with indeterminate nodules., Methods: Patients who underwent surgery for a thyroid nodule between 2003 and 2012 at a tertiary care center were prospectively enrolled. Stored nodule samples were retrospectively genotyped for the BRAF(V600E) mutation. BRAF(V600E) status, demographics, cytologic and histopathologic findings, and choice of initial surgery were examined., Results: A total of 960 patients were enrolled, of which 310 (32%) had an indeterminate nodule. The BRAF(V600E) mutation was identified in 13 patients (4%), 12 of whom had either cytologic atypia or were Bethesda category V. Three percent of Bethesda category III or IV nodules that were malignant harbored the mutation compared with 42% of Bethesda category V malignancies. Nuclear grooves (P = .030), pseudoinclusions (P < .001), and oval nuclei (P = .022) were all more common among BRAF(V600E) mutants. The sensitivities of using BRAF testing alone, cytologic atypia/Bethesda category V classification, or both, were 15%, 73%, and 76%, respectively. Twelve of the 13 BRAF(V600E) mutants had total thyroidectomies initially due to worrisome cytologic features, and therefore the initial management of only one patient would have been altered if BRAF(V600E) testing had been performed preoperatively., Conclusions: Preoperative mutation screening for BRAF(V600E) does not meaningfully improve risk stratification and is unlikely to alter the initial management of patients with indeterminate nodules., (Copyright © 2012 American Cancer Society.)

Across two studies, we examined the association between adiposity, restrictive feeding practices and cortical processing bias to food stimuli in children. We assessed P3b event-related potential (ERP) during visual oddball tasks in which the frequently presented stimulus was non-food and the infrequently presented stimulus was either a food (Study 1) or non-food (Study 2) item. Children responded to the infrequently presented stimulus and accuracy and speed responses were collected. Restrictive feeding practices, children's height and weight were also measured. In Study 1, the difference in P3b amplitude for infrequently presented food stimuli, relative to frequently presented non-food stimuli, was negatively associated with adiposity and positively associated with restrictive feeding practices after controlling for adiposity. There was no association between P3b amplitude difference and adiposity or restriction in Study 2, suggesting that the effects seen in Study 1 were not due to general attentional processes. Taken together, our results suggest that attentional salience, as indexed by the P3b amplitude, may be important for understanding the neural correlates of adiposity and restrictive feeding practices in children., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

The tendency to perceive caregivers in highly positive terms and to perceive the self as strong and problem-free are two facets of the positive bias characteristic of a dismissing attachment classification in adulthood. However, this link has not yet been examined in children. We evaluated the association between dismissing attachment and positive bias in school-aged children's reports of their own emotional experience and their parental care, hypothesizing that: (1) compared to secure children, dismissing children would underreport their subjective distress relative to physiological indicators of distress, and (2) dismissing children would report that their parents were warmer/more caring than would secure children. Ninety-seven children between the ages of 8 and 12 completed the Child Attachment Interview, reports of maternal and paternal care, and a psychophysiological threat paradigm. Compared to secure children, dismissing children reported less distress than their startle responses during threat would suggest. In other words, dismissing children showed a greater divergence between subjective and physiological emotional response. Dismissing children rated their parents as warmer and more caring as compared to secure children's ratings. Results provide support for the association between dismissing attachment and inflated positivity on child-report measures of parental care and emotional experience. Implications of the study's findings for attachment theory are discussed.

Background: Clinicians have difficulty in identifying patients that are unlikely to adhere to hypertension self-management. Identifying non-adherence is essential to addressing suboptimal blood pressure control and high costs., Objectives: 1) To identify risk factors associated with non-adherence to three key self-management behaviors in patients with hypertension: proper medication use, diet, and exercise; 2) To evaluate the extent to which an instrument designed to identify the number of risk factors present for non-adherence to each of the three hypertension self-management behaviors would be associated with self-management non-adherence and blood pressure., Design: Cross-sectional analysis of randomized trial data., Patients: Six hundred and thirty-six primary care patients with hypertension., Measurements: 1) Demographic, socioeconomic, psychosocial, and health belief-related factors; 2) measures of self-reported adherence to recommended medication use, diet recommendations, and exercise recommendations, all collected at baseline assessment; 3) systolic blood pressure (SBP) and diastolic blood pressure (DBP)., Results: We identified patient factors associated with measures of non-adherence to medications, diet, and exercise in hypertension. We then combined risk factors associated with ≥1 adherence measure into an instrument that generated three composite variables (medication, diet, and exercise composites), reflecting the number of risk factors present for non-adherence to the corresponding self-management behavior. These composite variables identified subgroups with higher likelihood of medication non-adherence, difficulty following diet recommendations, and difficulty following exercise recommendations. Composite variable levels representing the highest number of self-management non-adherence risk factors were associated with higher SBP and DBP., Conclusions: We identified factors associated with measures of non-adherence to recommended medication use, diet, and exercise in hypertension. We then developed an instrument that was associated with non-adherence to these self-management behaviors, as well as with blood pressure. With further study, this instrument has potential to improve identification of non-adherent patients with hypertension.

Since 1996, states have been implementing and enhancing their graduated driver licensing (GDL) programs. Increased licensing restrictions could steer new drivers to bypass training and licensing altogether. Unlicensed driving is associated with increased fatal crashes and high-risk behaviors that have been shown to adversely affect passenger safety behaviors like restraint use. The objective of this study was to assess the impact of varying state level GDL programs on rates of unlicensed driving and on passenger restraint use. De-identified data from the National Highway Traffic Safety Administration's Fatality Analysis Reporting System from years 1996-2010 was analyzed. Fatal crashes involving drivers (15-24 yrs) and their passengers (15-24 yrs) were included. Using a validated system, each state's GDL laws at a given month were rated as poor, marginal, fair, or good. The association between GDL strength and unlicensed driving was analyzed graphically and by chi-square test. Multivariate logistic regression with generalized estimating equations were undertaken to assess the relationship between GDL strength and passenger restraint use. From January 1996 to December 2010, 26,504 (23.4%) passengers were involved in fatal crashes taking place in states with GDL programs rated poor, 21,366(18.9%) marginal, 33,603 (29.6%) fair, and 31,903 (28.1%) good. Rates of unlicensed driving ranged from 16.4% in state-months rated marginal versus 21.5% in state-months rated good (p<0.001). In the multivariate model, compared to states with poor GDL ratings, each additional rating boost was associated with an increased odds of passenger safety restraint use (OR 1.15, 95% CI 1.13-1.18). Our findings suggest that stronger GDL law can mitigate passenger risk in fatal crashes by encouraging passenger restraint use. Our study provides evidence that stronger legislation in these states may reduce overall risk to young drivers and their passengers.

We employed event-related potentials to examine the feedback-related negativity (FRN), during a non-learning reward versus non-reward task. We compared 10-12-year-old, 13-14-year-old, and 15-17-year-old youth (n = 91). Age effects included a larger FRN for younger age groups, regardless of feedback type, and a decrease in peak latency for feedback, across age groups as a linear trend. Males showed larger responses irrespective of feedback type and longer latency for rewarded feedback. Source modeling revealed reward/non-reward differences in the anterior cingulate cortex (ACC) and orbitofrontal cortex, most strongly in the subgenual ACC. Males showed more subgenual ACC activity for feedback overall.

Risk-taking propensity is a pivotal facet of motor vehicle crash involvement and subsequent traumatic injury in adolescents. Clinical encounters are important opportunities to identify teens with high risk-taking propensity who may later experience serious injury. Our objective was to compare self-reports of health risk behavior with performance on the Balloon Analog Risk Task (BART), a validated metric of risk-taking propensity, in adolescents during a clinical encounter. 100 adolescent patients from a hospital emergency department and adolescent health clinic completed a computer-based survey of self-reported risk behaviors including substance use behaviors and behaviors that influence crash involvement. They then completed the BART, a validated laboratory-based risk task in which participants earn points by pumping up a computer-generated balloon with greater pumps leading to increased chance of balloon explosion. 20 trials were undertaken. Mean number of pumps on the BART showed a correlation of .243 (p=.015) with self-reported driver/passenger behaviors and attitudes towards driving that influence risk of crash injury. Regression analyses showed that self-reports of substance use and mean number of pumps on the BART uniquely predict self-reports of behaviors influencing the risk of crash injury. The BART is a promising correlate of real-world risk-taking behavior related to traffic safety. It remains a valid predictor of behaviors influencing risk of crash injury when using just 10 trials, suggesting its utility as a quick and effective screening measure for use in busy clinical environments. This tool may be an important link to prevention interventions for those most at-risk for future motor vehicle crash involvement and injury.

Internet use and video-game playing are experiencing rapid growth among both youth and adult populations. Research suggests that a minority of users experience symptoms traditionally associated with substance-related addictions. Mental health professionals, policy makers and the general public continue to debate the issue of Internet addiction (IA) and problematic video-game playing (PVG). This review identifies existing studies into the clinical and biological characteristics of these disorders that may help guide decisions as to whether or not IA and PVG should be grouped together with substance use disorders (SUDs).

Attachment representations are thought to provide a cognitive-affective template, guiding the way individuals interact with unfamiliar social partners. To examine the neural correlates of this process, we sampled event-related potentials (ERPs) during exclusion by unfamiliar peers to differentiate insecure-dismissing from securely attached youth, as indexed by the child attachment interview. Thirteen secure and 10 dismissing 11- to 15-year-olds were ostensibly connected with two peers via the Internet to play a computerized ball-toss game. Actually, peers were computer generated, first distributing the ball evenly, but eventually excluding participants. Afterward children rated their distress. As in previous studies, distress was related to a negative left frontal slow wave (500-900 ms) during rejection, a waveform implicated in negative appraisals and less approach motivation. Though attachment classifications were comparable in frontal ERPs and distress, an attachment-related dismissal dimension predicted a negative left frontal slow wave during rejection, suggesting that high dismissal potentially involves elevated anticipation of rejection. As expected, dismissal and self-reported distress were uncorrelated. Yet, a new approach to quantifying the dissociation between self-reports and rejection-related ERPs revealed that dismissal predicted underreporting of distress relative to ERPs. Our findings imply that evaluations and regulatory strategies linked to attachment generalize to distressing social contexts in early adolescence.

Background: Few studies have addressed comorbid antisocial personality disorder (ASPD) and marijuana dependence in young adults, and results from previous studies are inconsistent., Objectives: This study evaluated differences in pretreatment characteristics and treatment outcomes between marijuana-dependent young adults with and without ASPD., Methods: Data for this study were derived from a randomized trial, in which marijuana-dependent young adults (n = 136) between 18 and 25 years of age were randomized to four behavioral conditions: (1) MET/CBT with CM, (2) MET/CBT without CM, (3) DC with CM, and (4) DC without CM., Results: Forty-four percent of the participants met DSM-IV-TR criteria for ASPD. ASPD clients had significantly more lifetime alcohol dependence disorders, marijuana use in the 28 days pretreatment, arrests, and assault and weapon charges compared to those without ASPD. ASPD clients did not differ in retention or substance use outcomes at 8 weeks posttreatment or the 6-month follow-up. In general, both groups had more attendance in the voucher condition, but there were no significant ASPD by treatment interactions., Conclusions: These data suggest that marijuana-dependent young adults with comorbid ASPD do not necessarily have poorer retention or substance use outcomes compared with marijuana-dependent young adults who do not have ASPD when treated in a well-defined behavioral therapy protocol., Scientific Significance: Previous research has shown increased risks for clients with comorbid ASPD and marijuana dependence; however, our findings suggest that specialized programs for clients with ASPD may not be necessary if they are provided with empirically supported, structured treatments.

Background: A long line of theoretical and empirical evidence implicates negative reinforcement as a process underlying the etiology and maintenance of risky alcohol use behaviors from adolescence through emerging adulthood. However, the bulk of this literature has relied on self-report measures, and there is a notable absence of behavioral modes of assessments of negative reinforcement-based alcohol-related risk-taking. To address this clear gap in the literature, the current study presents the first published data on the reliability and validity of the Maryland Resource for the Behavioral Utilization of the Reinforcement of Negative Stimuli (MRBURNS), which is a modified version of the positive reinforcement-based Balloon Analogue Risk Task (BART)., Methods: Participants included a convenience sample of 116 college freshmen ever regular drinkers (aged 18 to 19) who completed both behavioral tasks; self-report measures of negative reinforcement/avoidance constructs and of positive reinforcement/appetitive constructs to examine convergent validity and discriminant validity, respectively; and self-report measures of alcohol use, problems, and motives to examine criterion validity., Results: The MRBURNS evidenced sound experimental properties and reliability across task trials. In support of convergent validity, risk-taking on the MRBURNS correlated significantly with negative urgency, difficulties in emotion regulation, and depressive and anxiety-related symptoms. In support of discriminant validity, performance on the MRBURNS was unrelated to risk-taking on the BART, sensation seeking, and trait impulsivity. Finally, pertaining to criterion validity, risk-taking on the MRBURNS was related to alcohol-related problems but not heavy episodic alcohol use. Notably, risk-taking on the MRBURNS was associated with negative reinforcement-based but not with positive reinforcement-based drinking motives., Conclusions: Data from this initial investigation suggest the utility of the MRBURNS as a behavioral measure of negative reinforcement-based risk-taking that can provide a useful complement to existing self-report measures to improve our understanding of the relationship between avoidant reinforcement processes and risky alcohol use., (Copyright © 2012 by the Research Society on Alcoholism.)

Background: Problems with reward system function have been posited as a primary difficulty in autism spectrum disorders. The current study examined an electrophysiological marker of feedback monitoring, the feedback-related negativity (FRN), during a monetary reward task. The study advanced prior understanding by focusing exclusively on a developmental sample, applying rigorous diagnostic characterization and introducing an experimental paradigm providing more subtly different feedback valence (reward versus non-reward instead of reward versus loss)., Methods: Twenty-six children with autism spectrum disorder and 28 typically developing peers matched on age and full-scale IQ played a guessing game resulting in monetary gain ("win") or neutral outcome ("draw"). ERP components marking early visual processing (N1, P2) and feedback appraisal (FRN) were contrasted between groups in each condition, and their relationships to behavioral measures of social function and dysfunction, social anxiety, and autism symptomatology were explored., Results: FRN was observed on draw trials relative to win trials. Consistent with prior research, children with ASD exhibited a FRN to suboptimal outcomes that was comparable to typical peers. ERP parameters were unrelated to behavioral measures., Conclusions: Results of the current study indicate typical patterns of feedback monitoring in the context of monetary reward in ASD. The study extends prior findings of normative feedback monitoring to a sample composed exclusively of children and demonstrates that, as in typical development, individuals with autism exhibit a FRN to suboptimal outcomes, irrespective of neutral or negative valence. Results do not support a pervasive problem with reward system function in ASD, instead suggesting any dysfunction lies in more specific domains, such as social perception, or in response to particular feedback-monitoring contexts, such as self-evaluation of one's errors.

Background: A recent review evaluated the comparative effectiveness of angiotensin-converting enzyme inhibitors (ACE-Is) and angiotensin II receptor blockers (ARBs) in patients with or at high risk for stable ischemic heart disease (IHD). The prioritization of future research needs has customarily been an informal process that is not responsive to the needs of all relevant stakeholders., Methods: As part of the Agency for Healthcare Research and Quality Effective Healthcare Program, the Duke Evidence-Based Practice Center engaged a diverse stakeholder group in 3 exercises designed to prioritize future research needs pertaining to the comparative effectiveness of ACE-I/ARB in patients with stable IHD., Results: Our stakeholders prioritized the following areas of research pertaining to the comparative effectiveness of ACE-I/ARB in stable IHD: (1) strategies to enhance greater evidence-based use, (2) impact of adherence on effectiveness or harms, (3) impact of comorbidities on effectiveness or harms, (4) medication impact on patient quality of life, (5) impact of demographic differences on effectiveness or harms, and (6) medication impact on incidence of new diagnoses. This project also yielded suggestions regarding potential study designs to address these future research needs., Conclusions: Our stakeholders prioritized research designed to facilitate (1) tailored ACE-I/ARB treatment based on individual patient characteristics and (2) implementation of ACE-I/ARB use among patients most likely to benefit. With respect to suggested study designs, it was felt that analysis of existing data would sufficiently address many of the top-tier future research needs (FRNs)., (Copyright © 2012 Mosby, Inc. All rights reserved.)

Purpose: Indeterminate thyroid lesions on fine needle aspiration (FNA) harbor malignancy in about 25% of cases. Hemi- or total thyroidectomy has, therefore, been routinely advocated for definitive diagnosis. In this study, we analyzed miRNA expression in indeterminate FNA samples and determined its prognostic effects on final pathologic diagnosis., Experimental Design: A predictive model was derived using 29 ex vivo indeterminate thyroid lesions on FNA to differentiate malignant from benign tumors at a tertiary referral center and validated on an independent set of 72 prospectively collected in vivo FNA samples. Expression levels of miR-222, miR-328, miR-197, miR-21, miR-181a, and miR-146b were determined using reverse transcriptase PCR. A statistical model was developed using the support vector machine (SVM) approach., Results: A SVM model with four miRNAs (miR-222, miR-328, miR-197, and miR-21) was initially estimated to have 86% predictive accuracy using cross-validation. When applied to the 72 independent in vivo validation samples, performance was actually better than predicted with a sensitivity of 100% and specificity of 86%, for a predictive accuracy of 90% in differentiating malignant from benign indeterminate lesions. When Hurthle cell lesions were excluded, overall accuracy improved to 97% with 100% sensitivity and 95% specificity., Conclusions: This study shows that that the expression of miR-222, miR-328, miR-197, and miR-21 combined in a predictive model is accurate at differentiating malignant from benign indeterminate thyroid lesions on FNA. These findings suggest that FNA miRNA analysis could be a useful adjunct in the management algorithm of patients with thyroid nodules., (©2012 AACR.)

Concern for the impact of prenatal cocaine exposure (PCE) on human language development is based on observations of impaired performance on assessments of language skills in these children relative to non-exposed children. We investigated the effects of PCE on speech processing ability using event-related potentials (ERPs) among a sample of adolescents followed prospectively since birth. This study presents findings regarding cortical functioning in 107 prenatally cocaine-exposed (PCE) and 46 non-drug-exposed (NDE) 13-year-old adolescents. PCE and NDE groups differed in processing of auditorily presented non-words at very early sensory/phonemic processing components (N1/P2), in somewhat higher-level phonological processing components (N2), and in late high-level linguistic/memory components (P600). These findings suggest that children with PCE have atypical neural responses to spoken language stimuli during low-level phonological processing and at a later stage of processing of spoken stimuli., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Young unlicensed drivers are more likely to be in fatal crashes and to engage in high-risk driving behaviors like impaired driving, speeding, and driving unrestrained. In a crash context, the influence of these high-risk behaviors may spillover to adversely affect passenger safety restraint use. We conducted an analysis of the Fatality Analysis Reporting System from years 1996-2008. Fatal crashes involving a driver aged 15-24 years and at least one passenger aged 15-24 years were included. Logistic regression with generalized estimating equations was undertaken to assess the effect of unlicensed driving on passenger restraint use. We controlled for established predictors of passenger restraint use including driver restraint use, gender, number of occupants, driver drinking, number of occupants, crash year, and crash location (rural vs. urban). 102,092 passengers were involved in fatal crashes during the time period with 64,803 unique drivers. 6,732 (10.51%) were never licensed drivers and 5,603 (8.8%) were drivers with suspended, revoked, or expired licenses. Rates of unlicensed driving ranged from 17.7% to 22.1% and increased over time. While passengers in fatal crashes averaged a mere 40.9% restraint use, passengers of never and invalidly licensed drivers had a further decreased odds of wearing a safety restraint (OR 0.73, 95% CI 0.69-0.77, p<0.001) and (OR 0.84, 95% CI 0.79-0.90, p<0.001). Unlicensed driving is involved in a disproportionate and increasing number of preventable crash fatalities and plays a detrimental role in the lifesaving safety behaviors of their passengers. Our findings highlight an alarming peer influence between unlicensed drivers and passengers, placing increased emphasis on the need to better understand and characterize this present and growing threat.

False discovery rate (FDR) is a multiple comparison procedure that targets the expected proportion of false discoveries among the discoveries. Employing FDR methods in event-related potential (ERP) research provides an approach to explore new ERP paradigms and ERP-psychological trait/behavior relations. In Study 1, we examined neural responses to escape behavior from an aversive noise. In Study 2, we correlated a relatively unexplored trait dimension, ostracism, with neural response. In both situations we focused on the frontal cortical region, applying a channel by time plots to display statistically significant uncorrected data and FDR corrected data, controlling for multiple comparisons.

Evidence from behavioral and neuroimaging studies suggest that atypical amygdala function plays a critical role in the development of autism spectrum disorders (ASD). The handful of psychophysiological studies examining amygdala function in ASD using classical fear conditioning paradigms have yielded discordant results. We recorded skin conductance response (SCR) during a simple discrimination conditioning task in 30 children and adolescents (ages 8-18) diagnosed with high-functioning ASD and 30 age- and IQ-matched, typically developing controls. SCR response in the ASD group was uniquely and positively associated with social anxiety; and negatively correlated with autism symptom severity, in particular with social functioning. Fear conditioning studies have tremendous potential to aid understanding regarding the amygdale's role in the varied symptom profile of ASD. Our data demonstrate that such studies require careful attention to task-specific factors, including task complexity; and also to contributions of dimensional, within-group factors that contribute to ASD heterogeneity., (Copyright © 2011, International Society for Autism Research, Wiley-Liss, Inc.)

Adolescence is a period of development in which peer relationships become especially important. A computer-based game (Cyberball) has been used to explore the effects of social exclusion in adolescents and adults. The current functional magnetic resonance imaging (fMRI) study used Cyberball to extend prior work to the cross-sectional study of younger children and adolescents (7 to 17 years), identifying age-related changes in the neural correlates of social exclusion across the important transition from middle childhood into adolescence. Additionally, a control task illustrated the specificity of these age-related changes for social exclusion as distinct from expectancy violation more generally. During exclusion, activation in and functional connectivity between ventrolateral prefrontal cortex and ventral anterior cingulate cortex increased with age. These effects were specific to social exclusion and did not exist for expectancy violation. Our results illustrate developmental changes from middle childhood through adolescence in both affective and regulatory brain regions during social exclusion., (2011 Blackwell Publishing Ltd.)

Clinical inertia represents a barrier to hypertension management. As part of a hypertension telemanagement trial designed to overcome clinical inertia, we evaluated study physician reactions to elevated home blood pressures. We studied 296 patients from the Hypertension Intervention Nurse Telemedicine Study who received telemonitoring and study physician medication management. When a patient's 2-week mean home blood pressure was elevated, an "intervention alert" prompted study physicians to consider treatment intensification. We examined treatment intensification rates and subsequent blood pressure control. Patients generated 1216 intervention alerts during the 18-month intervention. Of 922 eligible intervention alerts, study physicians intensified treatment in 374 (40.6%). Study physician perception that home blood pressure was acceptable was the most common rationale for nonintensification (53.7%). When "blood pressure acceptable" was the reason for not intensifying treatment, the mean blood pressure was lower than for intervention alerts where treatment intensification occurred (135.3/76.7 versus 143.2/80.6 mm Hg; P<0.0001). Blood pressure acceptable intervention alerts were associated with the lowest incidence of repeat alerts (hazard ratio: 0.69 [95% CI: 0.58 to 0.83]), meaning that the patient home blood pressure was less likely to subsequently rise above goal, despite apparent clinical inertia. This telemedicine intervention targeting clinical inertia did not guarantee treatment intensification in response to elevated home blood pressures. However, when physicians did not intensify treatment, it was because blood pressure was closer to an acceptable threshold, and repeat blood pressure elevations occurred less frequently. Failure to intensify treatment when home blood pressure is elevated may, at times, represent good clinical judgment, not clinical inertia.

The ability to regulate one's emotions is critical to mental health and well-being, and is impaired in a wide range of psychopathologies, some of which initially manifest in childhood or adolescence. Cognitive reappraisal is a particular approach to emotion regulation frequently utilized in behavioral psychotherapies. Despite a wealth of research on cognitive reappraisal in adults, little is known about the developmental trajectory of brain mechanisms subserving this form of emotion regulation in children. In this functional magnetic resonance imaging study, we asked children and adolescents to up-and down-regulate their response to disgusting images, as the experience of disgust has been linked to anxiety disorders. We demonstrate distinct patterns of brain activation during successful up- and down-regulation of emotion, as well as an inverse correlation between activity in ventromedial prefrontal cortex (vmPFC) and limbic structures during down-regulation, suggestive of a potential regulatory role for vmPFC. Further, we show age-related effects on activity in PFC and amygdala. These findings have important clinical implications for the understanding of cognitive-based therapies in anxiety disorders in childhood and adolescence.

The present study aimed to explore the neural correlates of two characteristic deficits in autism spectrum disorders (ASD); social impairment and restricted, repetitive behavior patterns. To this end, we used comparable experiences of social exclusion and rule violation to probe potentially atypical neural networks in ASD. In children and adolescents with and without ASD, we used the interactive ball-toss game (Cyberball) to elicit social exclusion and a comparable game (Cybershape) to elicit a non-exclusive rule violation. Using functional magnetic resonance imaging (fMRI), we identified group differences in brain responses to social exclusion and rule violation. Though both groups reported equal distress following exclusion, the right insula and ventral anterior cingulate cortex were hypoactive during exclusion in children with ASD. In rule violation, right insula and dorsal prefrontal cortex were hyperactive in ASD. Right insula showed a dissociation in activation; it was hypoactive to social exclusion and hyperactive to rule violation in the ASD group. Further probed, different regions of right insula were modulated in each game, highlighting differences in regional specificity for which subsequent analyses revealed differences in patterns of functional connectivity. These results demonstrate neurobiological differences in processing social exclusion and rule violation in children with ASD.

Despite significant social difficulties, children with autism spectrum disorder (ASD) are vulnerable to the effects of social exclusion. We recorded EEG while children with ASD and typical peers played a computerized game involving peer rejection. Children with ASD reported ostracism-related distress comparable to typically developing children. Event-related potentials (ERPs) indicated a distinct pattern of temporal processing of rejection events in children with ASD. While typically developing children showed enhanced response to rejection at a late slow wave indexing emotional arousal and regulation, those with autism showed attenuation at an early component, suggesting reduced engagement of attentional resources in the aversive social context. Results emphasize the importance of studying the time course of social information processing in ASD; they suggest distinct mechanisms subserving similar overt behavior and yield insights relevant to development and implementation of targeted treatment approaches and objective measures of response to treatment.

Individuals with high-functioning autism often display deficits in social interactions and high-level cognitive functions. Such deficits may be influenced by poor ability to process feedback and rewards. The feedback-related negativity (FRN) is an event-related potential (ERP) that is more negative following losses than gains. We examined FRN amplitude in 25 individuals with Autism Spectrum Disorder (ASD) and 25 age- and IQ-matched typically developing control participants who completed a guessing task with monetary loss/gain feedback. Both groups demonstrated a robust FRN that was more negative to loss trials than gain trials; however, groups did not differ in FRN amplitude as a function of gain or loss trials. N1 and P300 amplitudes did not differentiate groups. FRN amplitude was positively correlated with age in individuals with ASD, but not measures of intelligence, anxiety, behavioral inhibition, or autism severity. Given previous findings of reduced-amplitude error-related negativity (ERN) in ASD, we propose that individuals with ASD may process external, concrete, feedback similar to typically developing individuals, but have difficulty with internal, more abstract, regulation of performance., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Social exclusion inherently involves an element of expectancy violation, in that we expect other people to follow the unwritten rule to include us in social interactions. In this functional magnetic resonance imaging (fMRI) study, we employed a unique modification of an interactive virtual ball-tossing game called "Cyberball" (Williams et al., 2000) and a novel paradigm called "Cybershape," in which rules are broken in the absence of social exclusion, to dissociate brain regions that process social exclusion from rule violations more generally. Our Cyberball game employed an alternating block design and removed evoked responses to events when the participant was throwing the ball in inclusion to make this condition comparable to exclusion, where participants did not throw. With these modifications, we replicated prior findings of ventral anterior cingulate cortex (vACC), insula, and posterior cingulate cortex activity evoked by social exclusion relative to inclusion. We also identified exclusion-evoked activity in the hippocampi, left ventrolateral prefrontal cortex, and left middle temporal gyrus. Comparing social exclusion and rule violation revealed a functional dissociation in the active neural systems as well as differential functional connectivity with vACC. Some overlap was observed in regions differentially modulated by social exclusion and rule violation, including the vACC and lateral parietal cortex. These overlapping brain regions showed different activation during social exclusion compared to rule violation, each relative to fair play. Comparing activation patterns to social exclusion and rule violation allowed for the dissociation of brain regions involved in the experience of exclusion versus expectancy violation., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Understanding hetereogeneity in symptom expression across the autism spectrum disorders (ASD) is a major challenge for identifying causes and effective treatments. In 40 children and adolescents diagnosed with ASD and 37 IQ-and age-matched comparison participants (the TYP group), we found no differences in summary measures on an experimental risk-taking task. However, anxiety and IQ predicted risk-taking only in the ASD group. Risk-taking was correlated with behavioral inhibition in the ASD group and behavioral activation in the TYP group. We suggest that performance on the task was motivated by fear of failure in the ASD group and by sensitivity to reward in the TYP group. Behavioral markers of anxiety and cognitive ability may improve conceptualization of heterogeneity in ASD.

Clinical accounts of depression underscore its relation to negative emotional experiences; yet few empirical studies examine emotional experiences in adults with depression, with even less work on depression and emotion in children. Using a nonclinical sample of school-aged children (n = 89) ages 8 to 12, this study evaluated whether greater mood symptoms were associated with more or less intense emotional reactions (measured via psychophysiology, subjective report, and behavior) in response to a threat paradigm. Results indicated that greater negative mood symptoms were associated with larger startle magnitude responses during threat, increased self-reports of negative emotion, and greater likelihood of crying and stopping the paradigm prematurely.

One of the primary functions of the attachment behavioral system is to regulate emotional experience under conditions of threat. Although research supports this association among infants and adults, few studies examine the relation between emotion and attachment in middle childhood. This study examined the concurrent associations among children's attachment organization and three indices of emotion reactivity/regulation: self- and parent-assessments of emotion, neuroendocrine reactivity, and fear-potentiated startle response. Ninety-seven 8- to 12-year-old children completed the Child Attachment Interview (CAI) and a fear-potentiated startle paradigm on separate occasions, with salivary cortisol assessed before and after each assessment. Greater attachment security was related to greater child-reported positive trait- and state-level emotion, lower pre-CAI cortisol levels, higher initial startle magnitude during threat, and a faster decrease in startle magnitude during threat. The findings provide initial support that attachment security is related to select measures of emotion, though different methods of assessment yielded discrepant findings. The findings are discussed in terms of their contribution to theory and research examining attachment and emotion., (Copyright 2010 APA)

The Duke University Medical Center Internal Medicine Residency Program did not reach its anticipated quota of applicants during the 2008 National Residency Matching Program. Post-Match feedback regarding workload prompted an effort to redesign the general medicine service. As part of that effort, Duke program leaders sought to learn how peer programs accommodated Accreditation Council for Graduate Medical Education (ACGME) regulations. They launched the Resident Site Visit Project (RSVP).In 2008, Duke resident teams visited six other academic internal medicine residency programs based in university hospitals in the eastern United States. They conducted a systematic survey using a standardized questionnaire, interviewed program leaders and residents, and observed workflow directly. The RSVP identified strategies for accommodating ACGME rules in service design and also highlighted challenges shared by all of the programs.Discussion of the shared challenges yielded six core principles that directly guided Duke's general medicine service redesign: emphasize patient safety, reduce resident work compression, create educational opportunities, ensure automatic duty hours compliance, preserve essential program attributes, and involve stakeholders in the process of change.The Duke RSVP is an approach to programmatic change that applies information collected during site visits in defining core principles for program redesign. Collaboration between programs through resident site visits facilitates innovation, creates a foundation for change that increases stakeholder involvement, and generates opportunities for multicenter research.

This study examined neural activity with event-related potentials (ERPs) in middle childhood during a computer-simulated ball-toss game, Cyberball. After experiencing fair play initially, children were ultimately excluded by the other players. We focused specifically on “not my turn” events within fair play and rejection events within social exclusion. Dense-array ERPs revealed that rejection events are perceived rapidly. Condition differences (“not my turn” vs. rejection) were evident in a posterior ERP peaking at 420 ms consistent, with a larger P3 effect for rejection events indicating that in middle childhood rejection events are differentiated in <500 ms. Condition differences were evident for slow-wave activity (500-900 ms) in the medial frontal cortical region and the posterior occipital-parietal region, with rejection events more negative frontally and more positive posteriorly. Distress from the rejection experience was associated with a more negative frontal slow wave and a larger late positive slow wave, but only for rejection events. Source modeling with Geosouce software suggested that slow-wave neural activity in cortical regions previously identified in functional imaging studies of ostracism, including subgenual cortex, ventral anterior cingulate cortex, and insula, was greater for rejection events vs. “not my turn” events., (© 2010 Psychology Press)

The feedback-related negativity (FRN) is an event-related potential thought to reflect a reward prediction error, when an outcome is worse than expected. Behavior motivated by the avoidance of negative outcomes is sustained through negative reinforcement processes. Escaping or avoiding a negative outcome may be successful or not, resulting in an analogous situation to that which elicits the FRN. We observed that when expected avoidance of an aversive outcome fails to occur, there occurs a negative deflection in the frontocentral event-related potential at approximately 350 ms, but with a slow wave following. We suggest that the FRN may be considered an index of a broader class of reward-based learning that also includes avoiding negative outcomes as well as expecting positive ones.

We studied time-based neural activity with event-related potentials (ERPs) in young adults during a computer-simulated ball-toss game. Experiencing fair play initially, participants were ultimately excluded by other players. Dense-array ERPs showed time-dependent associations between slow-wave activity (580-900 ms) in left prefrontal/medial frontal cortical regions for exclusion events and self-reported distress. More subtle 'micro-rejections' during fair play showed a similar distress to ERP association (420-580 ms). In both cases, greater positive amplitude neural activity was associated with less post-exclusion distress. Findings suggest that rapidly occurring neural responses to social exclusion events are linked to individual differences in ostracism-related distress. Relations emerged even during fair play, providing a window into the neural basis of more subtle social-cognitive perceptual processes.

Background: Although others have reported national disparities in the quality of diabetes care between the Veterans Affairs (VA) and private health care delivery systems, it is not known whether these differences persist among internal medicine resident providers in academic settings., Objective: We compared the quality of diabetes primary care delivered by resident physicians in either a private academic health care system (AHS) or its affiliated VA health care system., Design: Cross-sectional observational study, Participants: We included patients who: had a diagnosis of diabetes, had >2 primary care visits with the same resident provider during 2005, and were not separately managed by an attending physician or endocrinologist. A total of 640 patients met our criteria and were included in the analysis., Measurements and Results: Compared to the VA, patients in the AHS were more likely to be younger, female, have fewer medications, and be treated with insulin, but had less comorbidity. Patients in the VA were more likely to be referred for an annual eye exam (94% vs. 78%), receive lipid screening (88% vs. 74%), receive proteinuria screening (63% vs. 34%), and receive a complete foot exam (85% vs. 32%) in analyses adjusted for patient demographics and comorbidities (p-value <0.001 for all comparisons). In adjusted analyses, there were no significant differences in HbA1(c), blood pressure, or LDL cholesterol control., Conclusions: In spite of similar resident providers and practice models, there were substantial differences in the diabetes quality of care delivered in the VA and AHS. Understanding how these factors influence subsequent practice patterns is an important area for study.

Event-related brain potentials were examined in 32 adolescents (50% female) from a high-risk sample, who were exposed to cocaine and other drugs prenatally. Adolescents were selected for extreme high- or low-risk behavior on the Balloon Analog Risk Task, a measure of real-world risk-taking propensity. The feedback error-related negativity (fERN), an event-related potential (ERP) that occurs when an expected reward does not occur, was examined in a game in which choices lead to monetary gains and losses with feedback delayed 1 or 2 s. The fERN was clearly visible in the fronto-central scalp region in this adolescent sample. Feedback type, feedback delay, risk status, and sex were all associated with fERN variability. Monetary feedback also elicited a P300-like component, moderated by delay and sex. Delaying reward feedback may provide a means for studying complementary functioning of dopamine and norepinephrine systems., (2009 S. Karger AG, Basel.)

If the mere exposure effect is based on implicit memory, recognition and affect judgments should be dissociated by experimental variables in the same manner as other explicit and implicit measures. Consistent with results from recognition and picture naming or object decision priming tasks (e.g., Biederman & E.E. Cooper, 1991, 1992; L.A. Cooper, Schacter, Ballesteros, & Moore, 1992), the present research showed that recognition memory but not affective preference was impaired by reflection or size transformations of three-dimensional objects between study and test. Stimulus color transformations had no effect on either measure. These results indicate that representations that support recognition memory code spatial information about an object's left-right orientation and size, whereas representations that underlie affective preference do not. Insensitivity to surface feature changes that do not alter object form appears to be a general characteristic of implicit memory measures, including the affective preference task.

The purpose of the present investigation was to explore further the known relationship between deliberate self-poisoning and social deprivation. Each individual who attended one of Cork city's three casualty departments following an act of deliberate self-poisoning in 1988 was examined. The place of residence (ward) of each city resident patient was established. The social status of the city's 34 wards was estimated using a number of indices obtained from the 1981 and 1986 census reports and social service records. A comparison was made between the 1988 self-poisoning rate for each ward and the rate found in a 1982 study of the city. Correlations between self-poisoning rate and seven social deprivation indices were found to be significant. Multiple regression, factor, and partial correlation analyses were carried out to examine more closely the interrelationships between the social deprivation indices. With respect to explaining the variation in the self-poisoning rate, unemployment alone performed almost as well as all of the indices together and as well as the factors derived using factor analysis. The correlation between unemployment and self-poisoning rate remained highly significant when the other related variables were controlled for. However, at fixed levels of unemployment, these variables were found to be independent of the self-poisoning rate. It is suggested that whereas clinical intervention may benefit the individual, deliberate self-poisoning as an issue requires a public health approach for its resolution.

This study investigates the level of suicide in Cork City during the 5-year period 1987/1991. Both male and female crude rates were higher than the corresponding national levels. The male/female ratio was 2.3:1, which is consistent with established findings. Vulnerability to suicide is most pronounced in 20-39 year old males and females in the 40-59 age category. There was some evidence of an increased risk of suicide among single elderly males; otherwise marital status was not a significant factor. A positive association was noted between unemployment and suicide rate for males. Drowning was used as the method of suicide by approximately half the male and female sub-groups; this was followed by hanging in the case of males and overdosing among females. However all suicide cases under 20 years of age used hanging.

One of the three national games of Ireland, hurling is a contact team sport (15 a side) played with a metre long ash stick and a small hard leather ball. Over a 12 month period, 413 players were treated for hurling-related injuries at Cork Regional Hospital. While hand and facial trauma predominate, the proportion between the two sites has changed substantially from previous reports with a reduction in the level of facial injuries. The wearing of a helmet, and optionally a supplementary faceguard, is seen to have contributed to this trend. Despite this welcome reduction of facial injuries, a certain resistance to the use of protective headgear is evident, particularly among older players.

This report presents findings from a 3-year investigation of patient turnover, morbidity and mortality in the department of geriatric medicine based at Cork University and St. Finbarr's Hospitals, Cork. A total of 3,977 patients were admitted during the study period. The majority were 70 years or over (89%), referred by a general practitioner (83%) and female (56%). Seventy-one percent of admissions were discharged home, a further 18% died within the unit while 11% were transferred to continuing care. The median duration of stay was ten days. Age, diagnosis and source of referral significantly influenced both patient outcome and duration of stay. Forty-seven percent of discharged patients were followed-up at either the day hospital or outpatient clinic. A morbidity profile was constructed for a representative sample of 318 patients. 52% of this sample had two or more significant diagnoses. Neurological disorders carried a particularly poor prognosis. The median duration of stay for patients transferred to an on-site long stay facility was approximately one year.

The incidence of cancer of the central nervous system (CNS) was established for the counties of Cork and Kerry using the Southern Tumour Registry data base. A total of 191 newly-diagnosed patients were identified over the five year period 1984-1988. This represents a crude annual incidence rate of 7.3 per 100,000 for males and 6.8 for females. When the incidence rates were adjusted using the accepted theoretical World Population, the annual rates were 6.7 and 6.4 for males and females respectively. These levels are higher than those reported for England and Wales (5.2 for males and 3.6 for females) and Scotland (5.9 for males and 4.2 for females). However the Irish rates are much lower than the most recent published statistics for Denmark which report rates of 12.9 for males and 11.8 for females. The risk of being affected by a CNS tumour increases substantially from 50 years onwards for a male and from 40 years on for females. The risk is seen to diminish for those aged 80 years or more. The most common locations of CNS tumours were the frontal, parietal and temporal lobes. Gliomas were by far the most common type of tumour.