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U.S. import and export price indexes replaced unit value indexes forty years ago, given quality concerns of mismeasurement due to unit value bias. The administrative trade data underlying the unit values have greatly improved since that time. The transaction records are now more detailed, available electronically, and compiled monthly with little delay. The data are used by academic researchers to calculate price measures, and unit value indexes based on trade data are used by other national statistical offices (NSOs). The U.S. Bureau of Labor Statistics is now evaluating whether replacing price indexes with unit value indexes for homogeneous products calculated from administrative trade data could expand the number of published official import and export price indexes. Using export transactions, the research calculates detailed unit value indexes from 200 + million trade records from 2012–2017 for 123 export product categories. Results show that 27 of the 123 unit value indexes are homogeneous and closely comparable to published official price indexes. This article presents the concepts and methods considered to calculate and evaluate the unit value indexes and to select the product categories that are homogeneous. Compared to official price indexes, export unit value indexes for the 27 5-digit BEA (U.S. Bureau of Economic Analysis) end-use product categories would deflate real exports of these goods by 13 percentage points less over the period. Incorporating these 27 indexes into the top-level XPI would increase the value of real exports of all merchandise goods by 2.6 percentage points at the end of 2017.

This pilot study explores the possibility of predicting post-concussion symptom recovery at one week post-injury using only objective diffusion tensor imaging (DTI) data inputs to a novel artificial intelligence (AI) system composed of Genetic Fuzzy Trees (GFT). Forty-three adolescents age 11 to 16 years with either mild traumatic brain injury or traumatic orthopedic injury were enrolled on presentation to the emergency department. Participants received a DTI scan three days post-injury, and their symptoms were assessed by the Post-Concussion Symptom Scale (PCSS) at 6 h and one week post-injury. The GFT system was trained using one-week total PCSS scores, 48 volumetric magnetic resonance imaging inputs, and 192 DTI inputs per participant over 225 training runs. Each training run contained a randomly selected 80% of the total sample followed by a 20% validation run. Over a different randomly selected sample distribution, GFT was also compared with six common classification methods. The cascading GFT structure controlled an effectively infinite solution space that classified participants as recovered or not recovered significantly better than chance. It demonstrated 100% and 62% classification accuracy in training and validation, respectively, better than any of the six comparison methods. Recovery sensitivity and specificity were 59% and 65% in the GFT validation set, respectively. These results provide initial evidence for the effectiveness of a GFT system to make clinical predictions of trauma symptom recovery using objective brain measures. Although clinical and research applications will necessitate additional optimization of the system, these results highlight the future promise of AI in acute care.

The Ruddlesden-Popper ($A_{n+1}B_{n}\text{O}_{3n+1}$) compounds are a highly tunable class of materials whose functional properties can be dramatically impacted by their structural phase $n$. The negligible energetic differences associated with forming a sample with a single value of $n$ versus a mixture of $n$ makes the growth of these materials difficult to control and can lead to local atomic-scale structural variation arising from small stoichiometric deviations. In this work, we present a Python analysis platform to detect, measure, and quantify the presence of different $n$-phases based on atomic-resolution scanning transmission electron microscopy (STEM) images in a statistically rigorous manner. We employ phase analysis on the 002 Bragg peak to identify horizontal Ruddlesden-Popper faults which appear as regions of high positive compressive strain within the lattice image, allowing us to quantify the local structure. Our semi-automated technique offers statistical advantages by considering effects of finite projection thickness, limited fields of view, and precise sampling rates. This method retains the real-space distribution of layer variations allowing for a spatial mapping of local $n$-phases, enabling both quantification of intergrowth occurrence as well as qualitative description of their distribution, opening the door to new insights and levels of control over a range of layered materials., 8 pages, 5 figures

The goals of the current study were to determine whether topological organization of brain structural networks is altered in youth with bipolar disorder, whether such alterations predict treatment outcomes, and whether they are normalized by treatment. Youth with bipolar disorder were randomized to double-blind treatment with quetiapine or lithium and assessed weekly. High-resolution MRI images were collected from children and adolescents with bipolar disorder who were experiencing a mixed or manic episode (n = 100) and healthy youth (n = 63). Brain networks were constructed based on the similarity of morphological features across regions and analyzed using graph theory approaches. We tested for pretreatment anatomical differences between bipolar and healthy youth and for changes in neuroanatomic network metrics following treatment in the youth with bipolar disorder. Youth with bipolar disorder showed significantly increased clustering coefficient (Cp) (p = 0.009) and characteristic path length (Lp) (p = 0.04) at baseline, and altered nodal centralities in insula, inferior frontal gyrus, and supplementary motor area. Cp, Lp, and nodal centrality of the insula exhibited normalization in patients following treatment. Changes in these neuroanatomic parameters were correlated with improvement in manic symptoms but did not differ between the two drug therapies. Baseline structural network matrices significantly differentiated medication responders and non-responders with 80% accuracy. These findings demonstrate that both global and nodal structural network features are altered in early course bipolar disorder, and that pretreatment alterations in neuroanatomic features predicted treatment outcome and were reduced by treatment. Similar connectome normalization with lithium and quetiapine suggests that the connectome changes are a downstream effect of both therapies that is related to their clinical efficacy.

OBJECTIVES: Altered activity in the ventrolateral prefrontal and anterior cingulate cortices, as well as subcortical and amygdala projection sites, were previously reported during a first manic episode in youth with bipolar disorder and observed to be associated with treatment response. To extend these findings, we investigated functional connectivity among these regions in first-episode manic participants who remitted after eight weeks of treatment compared to those that did not. METHODS: Forty-two participants with bipolar disorder (60% female) during their first manic episode were recruited and received eight weeks of treatment. Twenty-one remitted following treatment. Participants completed fMRI scans, at baseline and following eight weeks of treatment, while performing a continuous performance task with emotional and neutral distractors. A healthy comparison group (n=41) received fMRI evaluations at the same intervals. Differences in functional connectivity of the amygdala and caudate with the rostral anterior cingulate and ventrolateral prefrontal cortices at baseline (and changes in functional connectivity following treatment) were modeled between groups. RESULTS: At baseline, non-remitters showed an increase in positive connectivity between right anterior cingulate and caudate and a loss of negative connectivity between right anterior cingulate and amygdala, compared to healthy participants. Individuals who remitted following treatment showed an increase in negative connectivity between amygdala and left anterior cingulate eight weeks following treatment. CONCLUSIONS: Results provide evidence of alterations in anterior cingulate-amygdala and caudate functional connectivity in bipolar disorder non-remitters during a first manic episode and changes in anterior cingulate functional connectivity associated with remission suggesting targets to predict treatment response. Registered at ClinicalTrials.Gov; Functional and Neurochemical Brain Changes in First-episode Bipolar Mania. NCT00609193. URL: https://clinicaltrials.gov/ct2/show/NCT00609193?term=strakowski&rank=1

Disrupted topological organization of brain functional networks has been widely reported in bipolar disorder. However, the potential clinical implications of structural connectome abnormalities have not been systematically investigated. The present study included 109 unmedicated subjects with acute mania who were assigned to 8 weeks of treatment with quetiapine or lithium and 60 healthy controls. High resolution 3D-T1 weighted magnetic resonance images (MRI) were collected from both groups at baseline, week 1 and week 8. Brain networks were constructed based on the similarity of morphological features across brain regions and analyzed using graph theory approaches. At baseline, individuals with bipolar disorder illness showed significantly lower clustering coefficient (CName: Functional and Neurochemical Brain Changes in First-episode Bipolar Mania Following Successful Treatment with Lithium or Quetiapine. URL: https://clinicaltrials.gov/ .NCT00609193. Name: Neurofunctional and Neurochemical Markers of Treatment Response in Bipolar Disorder. URL: https://clinicaltrials.gov/ .NCT00608075.

Children of individuals with bipolar disorder (bipolar offspring) are at increased risk for developing mood disorders, but strategies to predict mood episodes are unavailable. In this study, we used support vector machine (SVM) to characterize the potential of proton magnetic resonance spectroscopy (1H-MRS) in predicting the first mood episode in youth bipolar offspring. From a longitudinal neuroimaging study, 19 at-risk youth who developed their first mood episode (converters), and 19 without mood episodes during follow-up (non-converters) were selected and matched for age, sex and follow-up time. Baseline 1H-MRS data were obtained from anterior cingulate cortex (ACC) and bilateral ventrolateral prefrontal cortex (VLPFC). Glutamate (Glu), myo-inositol (mI), choline (Cho), N-acetyl aspartate (NAA), and phosphocreatine plus creatine (PCr + Cr) levels were calculated. SVM with a linear kernel was adopted to classify converters and non-converters based on their baseline metabolites. SVM allowed the significant classification of converters and non-converters across all regions for Cho (accuracy = 76.0%), but not for other metabolites. Considering all metabolites within each region, SVM allowed the significant classification of converters and non-converters for left VLPFC (accuracy = 76.5%), but not for right VLPFC or ACC. The combined mI, PCr + Cr, and Cho from left VLPFC achieved the highest accuracy differentiating converters from non-converters (79.0%). Our findings from this exploratory study suggested that 1H-MRS levels of mI, Cho, and PCr + Cr from left VLPFC might be useful to predict the development of first mood episode in youth bipolar offspring using machine learning. Future studies that prospectively examine and validate these metabolites as predictors of mood episodes in high-risk individuals are necessary.

Disruptions in cognition are a clinically significant feature of bipolar disorder (BD). The effects of different treatments on these deficits and the brain systems that support them remain to be established.A continuous performance test was administered to 55 healthy controls and 71 acutely ill youths with mixed/manic BD to assess vigilance and working memory during task-based functional magnetic resonance imaging studies. Patients, who were untreated for at least 7 days at baseline, and controls were scanned at pretreatment baseline and at weeks 1 and 6. After baseline testing, patients (n = 71) were randomly assigned to 6-week double-blind treatment with lithium (n = 26; 1.0-1.2 mEq/L) or quetiapine (n = 45; 400-600 mg). Weighted seed-based connectivity (wSBC) was used to assess regional brain interactions during the attention task compared with the control condition.At baseline, youths with BD showed reduced connectivity between bilateral anterior cingulate cortex and both left ventral lateral prefrontal cortex and left insula and increased connectivity between left ventral lateral prefrontal cortex and left temporal pole, left orbital frontal cortex and right postcentral gyrus, and right amygdala and right occipital pole compared with controls. At 1-week follow-up, quetiapine, but not lithium, treatment led to a significant shift of connectivity patterns toward those of the controls. At week 6, compared with baseline, there was no difference between treatment conditions, at which time both patient groups showed significant normalization of brain connectivity toward that of controls.Functional alterations in several brain regions associated with cognitive processing and the integration of cognitive and affective processing were demonstrated in untreated youths with BD before treatment. Treatment reduced several of these alterations, with significant effects at week 1 only in the quetiapine treatment group. Normalization of functional connectivity might represent a promising biomarker for early target engagement in youth with BD.Multimodal Neuroimaging of Treatment Effects in Adolescent Mania; https://clinicaltrials.gov/; NCT00893581.

Over 2.3 million people in the United States live with bipolar disorder. Sixty percent of those with a bipolar disorder diagnosis attempt suicide at least once in their lifetime, and up to 19% die by suicide. However, the neurobiology of suicide attempts in bipolar disorder remains unclear. Here, we studied the neuroanatomical basis for suicide attempt history in bipolar disorder by measuring gray matter volumes (GMV) to identify differences in brain-volumes in 121 participants with bipolar disorder type I, and healthy participants (n=40). The bipolar group consisted of individuals with suicide attempt history (n=23) and no suicide attempt history (n=58). All participants completed behavioral/diagnostic assessments and MRI measures of GMV. We focused on a predefined frontolimbic circuitry in bipolar disorder versus (vs.) healthy to first identify diagnostic GMV markers and to specifically identify markers for suicide attempt history. We found reduced GMV markers for bipolar diagnosis (i.e., bipolarHighlightsSuicide is a major health problem especially in bipolar disorder but the neurobiological basis for suicide attempts remains obscure. We identified an anterior cingulate and dorsolateral prefrontal cortical volume correlate for suicide attempt history and suicidal ideation and thereby demonstrates a convergent brain marker for suicidal behaviors.

OBJECTIVE To examine effects of participating in collegiate football on neural health several years after retirement. We hypothesized that relative cortical thinning and loss of white matter integrity would be observed in former players. DESIGN Former NCAA Division I football players were compared with demographically similar track-and-field athletes with regard to cortical thickness and white matter integrity. SETTING Participants participated in MRI scans at the Center for Imaging Research at the University of Cincinnati. PARTICIPANTS Eleven former football players and 10 demographically similar track-and-field athletes. MAIN OUTCOME MEASURES Normalized cortical thickness was compared between groups using 2-tailed Student t test. As a secondary analysis, Spearman correlation coefficient was calculated between cortical thickness and number of concussions. Fractional anisotropy for regions-of-interest placed in frontal white matter tracts and internal capsule were compared between groups using 2-tailed Student t test. RESULTS Football players showed significantly lower cortical thickness within portions of both the frontal and temporal cortex. Affected frontal regions included left frontal pole and right superior frontal gyrus. Affected temporal regions included portions of the superior temporal gyrus, left inferior temporal gyrus, and right middle and superior temporal gyri. Cortical thickness inversely correlated with number of reported concussions over most of these regions. In addition, fractional anisotropy was lower in the right internal capsule of former football players, relative to controls. CONCLUSIONS These findings suggest that at least some consequences of high-level collegiate football play persist even after the cessation of regular head blows. Longer-term studies are warranted to examine potential cognitive and functional implications of sustained cortical atrophy.

Lateral and medial epicondylitis are common pathologic conditions and can be debilitating problems for athletes. Lateral epicondylitis occurs much more commonly than medial epicondylitis but both can create significant and persistent symptoms that limit performance. Nonoperative management is the mainstay of treatment for both conditions with more invasive treatments, including surgical intervention, reserved for recalcitrant cases. Both pathological entities can be operatively managed by using either percutaneous, formal open, or arthroscopic surgical techniques.

Objectives The objective of this clinical trial was to evaluate the long-term effect of endothelin receptor antagonism with bosentan on the morbidity and mortality of patients with severe chronic heart failure. Background Endothelin may play a role in heart failure, but short-term clinical trials with endothelin receptor antagonists have reported disappointing results. Long-term trials are lacking. Methods In 2 identical double-blind trials, we randomly assigned 1,613 patients with New York Heart Association functional class IIIb to IV heart failure and an ejection fraction Results Bosentan did not influence clinical status at 9 months in either trial (p = 0.928 and p = 0.263). In addition, 321 patients in the placebo group and 312 patients in the bosentan group died or were hospitalized for heart failure (hazard ratio [HR]: 1.01; 95% confidence interval [CI]: 0.86 to 1.18; p = 0.90). The bosentan group experienced fluid retention within the first 2 to 4 weeks, as evidenced by increased peripheral edema, weight gain, decreases in hemoglobin, and an increased risk of hospitalization for heart failure, despite intensification of background diuretics. During follow-up, 173 patients died in the placebo group and 160 patients died in the bosentan group (HR: 0.94; 95% CI: 0.75 to 1.16). About 10% of the bosentan group showed meaningful increases in hepatic transaminases, but none had acute or chronic liver failure. Conclusions Bosentan did not improve the clinical course or natural history of patients with severe chronic heart failure and but caused early and important fluid retention.

Functional magnetic resonance imaging (fMRI) and magnetic resonance spectroscopy (MRS) studies provide an exciting opportunity to understand the neural substrates that underlie the pathophysiology of bipolar disorder. This chapter reviews fMRI and MRS meta-analyses from the past 10 years to examine whether meta-analytic results differ from those otherwise expected on the basis of individual studies considered in isolation. Across different meta-analytic studies, and predominantly consistent with extant fMRI hypotheses, the most replicated findings are an overactivity of amygdala, especially during emotional processing, and underactivity of right ventrolateral prefrontal cortex during emotional or cognitive processing in bipolar disorder. These functional abnormalities appear to present during mania or depression, but not during euthymia, suggesting they are related to mood state, symptom severity, or both. Additionally, they appear to be rather specific to bipolar disorder, as opposed to major depressive disorder or schizophrenia. Recent prospective studies also suggest that clinical improvement associates with normalization of functional abnormalities or functional connectivity between prefrontal cortex and amygdala. MRS meta-analyses, although more limited than fMRI, suggest elevated glutamate in prefrontal cortex and decreased N-acetylaspartate in the basal ganglia and hippocampus. Additional studies employing multimodal imaging or longitudinal designs could help to advance the understanding of these neurofunctional and neurochemical brain abnormalities and to develop better preventive and therapeutic strategies for this condition.

This chapter provides a characterization of cognitive impairment in bipolar disorder and how emotions affect cognition and lead to cognitive biases. The Behavioral Approach System and Interactive Cognitive Model of bipolar disorder are reviewed, along with the newer Interactive Influence Model of Emotion and Cognition, which holds promise in future applications to mood disorders. These models provide a framework for the development and expansion of neurobiological models and psychotherapeutic interventions for bipolar disorder. The authors conclude by noting that, while models of bipolar disorder still need to be expanded to account for cognitive and behavioral influences beyond simple correlations with symptom outcomes, their importance is clearly demonstrated in the development of cognitive behavioral therapies, cognitive remediation therapies, and mindfulness-based cognitive therapies for bipolar disorder. The ability to test the efficacy of these, and other, cognitive behavioral therapeutics in controlled trials based on the predictions of well-characterized models of bipolar disorder will undoubtedly lead to advances in patient care.

The U.S. Bureau of Labor Statistics’ import and export price indexes (MXPI) are published from an ever decreasing sample relative to the size of trade. The Principal Federal Economic Indicator has an opportunity to retain and regain detailed MXPI using unit values calculated from comprehensive administrative trade data. Unit values are known to be biased, although bias is less prevalent among homogeneous products. This research presents a new methodological and statistical approach to blend unit values into official price indexes. First, a proof of concept for identifying homogeneous items is based on an analysis of two export products – dairy and vegetables – for 2015-16. The results provide a prototype and a roadmap for a consistent and testable approach that aligns with the concepts in official MXPI measures, maximizes the use of high-frequency data, and mitigates unit value bias. Applying the prototype, 52 of 142 import and 50 of 129 export 5-digit BEA End Use categories are identified as homogeneous using administrative data. This coverage accounts for 35 and 39 percent of the 2016 value of imports and exports, respectively. Incorporating unit values has the potential to deepen coverage and expand publication of detailed import and export price indexes. Institutional subscribers to the NBER working paper series, and residents of developing countries may download this paper without additional charge at www.nber.org.

Background Clinical remission is widely accepted as the primary target outcome for juvenile idiopathic arthritis (JIA). PR-COIN is a quality improvement collaborative that serves as a sample of pediatric rheumatology centers in North America. By measuring disease activity in practice using the ACR provisional criteria for Clinical Inactive Disease (CID), variation in patient outcomes has been previously observed between centers. Objectives The objective of this study was to evaluate differences in patient-level factors that may be driving center-level variation in JIA outcomes. Methods This study used cross-sectional data provided by PR-COIN that was collected by PR-COIN centers from March 2015 to May 2016. For each patient, sociodemographic, clinical, patient-reported, disease activity, and medication variables were extracted from the most recent encounter. Patients with disease duration less than 9 months were excluded. Patients were grouped by CID status (inactive vs active disease) and then compared using descriptive statistics, chi-square for categorical variables, and independent t-tests for continuous variables. Missing data were excluded with each analysis. Analyses were performed using R software. Results There were 2751 patients eligible for analysis from 14 centers, with 33 to 394 patients per center. We identified 1249 patients with inactive disease (47%) and 1428 patients with active disease (53%). Patients with inactive disease were younger (12 vs 13 years), more likely to have persistent oligoarticular subtype (33% vs 23%), and less likely to have enthesitis related arthritis (9% vs 14%). Patients with active disease had higher patient-reported measures of global assessment of disease activity, pain, and functional disability, as well as disease activity measures per definition. More medication usage was observed in patients with active disease compared to inactive disease across multiple categories, including both non-biologic DMARDs (45% vs. 32%) and biologic DMARDs (48% vs 35%). Conclusion This study demonstrates differences in sociodemographic, clinical, and medication factors between patients with inactive and active JIA. Further analysis is needed to adjust center-level measures of JIA disease activity using the observed differences in patient case-mix. By using population data to identify predictors of inactive disease in JIA, there is potential to develop and implement targeted clinical interventions to directly impact care and improve outcomes. Disclosure of Interests: Emily A. Smitherman: None declared, Bin Huang: None declared, Ronald Laxer Consultant for: Eli Lilly Canada, Alexion, Sanofi, C. April Bingham: None declared, Cagri Yildirim-Toruner: None declared, Beth Gottlieb: None declared, Jennifer E. Weiss: None declared, Tzielan Lee: None declared, Sheetal Vora: None declared, Jon (Sandy) Burnham: None declared, Julia G. Harris: None declared, Judyann C. Olson: None declared, Mileka Gilbert: None declared, Michelle Batthish Speakers bureau: Novartis, Abbvie, Michael Shishov: None declared, Dustin Fleck: None declared, Esi Morgan: None declared

Objectives We tested the hypothesis that, with treatment, functional magnetic resonance imaging (fMRI) regional brain activation in first-episode mania would normalize – i.e., that differences from healthy subjects would diminish over time, and would be associated with clinical remission status, potentially identifying neuroanatomic treatment response markers. Methods Forty-two participants with bipolar I disorder were recruited during their first manic episode, pseudo-randomized to open-label lithium or quetiapine, and followed for 8 weeks. fMRI scans were obtained at baseline and then after 1 and 8 weeks of treatment, while participants performed a continuous performance task with emotional distracters. Healthy participants received fMRI scans at these same intervals. Specific region-of-interest (ROI) activations within prefrontal emotional networks were assessed as potential measures of treatment response. Results ROI data were reduced using exploratory factor analysis, which identified five factors that were organizationally consistent with functional anatomic models of human emotion modulation. Half of the participants with bipolar disorder achieved remission by Week 8 and were contrasted with the other half that did not. Analyses demonstrated that, in the bipolar disorder group in general, treatment led to decreases in activation across brain regions toward healthy subject values. However, differences in activation changes were observed between subjects with bipolar disorder who did or did not achieve remission in subcortical and amygdala factors. Conclusions These findings provide evidence for potential neuroanatomic treatment response markers in first-episode bipolar disorder.

We examined the effects of lisdexamfetamine (LDX) treatment on ventral prefrontal cortex (VPFC) and striatal brain activation in binge eating disorder (BED). We hypothesized that participants with BED have an abnormal brain response to palatable food cues, and that VPFC and striatal regions would respond to such cues after LDX treatment. Twenty women with moderate to severe BED consented to a 12-week, open-label trial of LDX with fMRI before and after treatment. Twenty obese women without BED served as healthy controls and received one fMRI. LDX was started at 30 mg/d with a target of 70 mg/d at week 12. At baseline, women with BED showed greater activation in ventrolateral prefrontal cortex (VLPFC), striatum, and globus pallidus to food pictures and brain activation to food pictures predicted clinical outcome at 12 weeks. After 12 weeks of LDX treatment, BED women showed significant reductions in globus pallidus activation. Reductions in ventromedial prefrontal cortex (VMPFC) and thalamus activation specifically correlated with binge eating and obsessive-compulsive symptom reductions, respectively. Results suggest that BED is characterized by an abnormally large VPFC-subcortical brain response to palatable foods that LDX treatment helps modify. Moreover, VPFC-subcortical activation at baseline is a potential biomarker of LDX response.

Objective: To examine the effect of cost, a traditionally “inactive” trait of intervention, as contributor to the response to therapeutic interventions. Methods: We conducted a prospective double-blind study in 12 patients with moderate to severe Parkinson disease and motor fluctuations (mean age 62.4 ± 7.9 years; mean disease duration 11 ± 6 years) who were randomized to a “cheap” or “expensive” subcutaneous “novel injectable dopamine agonist” placebo (normal saline). Patients were crossed over to the alternate arm approximately 4 hours later. Blinded motor assessments in the “practically defined off” state, before and after each intervention, included the Unified Parkinson9s Disease Rating Scale motor subscale, the Purdue Pegboard Test, and a tapping task. Measurements of brain activity were performed using a feedback-based visual-motor associative learning functional MRI task. Order effect was examined using stratified analysis. Results: Although both placebos improved motor function, benefit was greater when patients were randomized first to expensive placebo, with a magnitude halfway between that of cheap placebo and levodopa. Brain activation was greater upon first-given cheap but not upon first-given expensive placebo or by levodopa. Regardless of order of administration, only cheap placebo increased activation in the left lateral sensorimotor cortex and other regions. Conclusion: Expensive placebo significantly improved motor function and decreased brain activation in a direction and magnitude comparable to, albeit less than, levodopa. Perceptions of cost are capable of altering the placebo response in clinical studies. Classification of evidence: This study provides Class III evidence that perception of cost is capable of influencing motor function and brain activation in Parkinson disease.

1. Dustin E. Fleck, MD* 2. Mark F. Hoeltzel, MD* 1. *Division of Pediatric Rheumatology, Department of Pediatrics, University of Michigan, Ann Arbor, MI * ADHD: : attention-deficit/hyperactivity disorder ANA: : antinuclear antibody POTS: : postural tachycardia syndrome Primary care clinicians are challenged to evaluate an array of different hand and foot color changes in kids, as treatment may range from reassurance of a benign, self-limited condition to further diagnostic evaluation and treatment with vasodilator pharmacotherapy. The most common and well-known causes of these color changes are Raynaud phenomenon, acrocyanosis, and the more rare but serious erythromelalgia. Clinicians should be aware of the clinical presentation, symptoms, etiologic origins, diagnostic evaluation, treatment, and potential complications of Raynaud phenomenon, acrocyanosis, and erythromelalgia in children. After completing this article, readers should be able to: 1. Identify the various causes of hand and foot color change in children and adolescents. 2. Recognize the differences in signs and symptoms of acrocyanosis, erythromelalgia, and Raynaud phenomenon. 3. Recognize complications associated with acrocyanosis, erythromelalgia, and Raynaud phenomenon. 4. Describe current treatments for acrocyanosis, erythromelalgia, and Raynaud phenomenon. ### Clinical Presentation Acrocyanosis is a clinically benign process that is known to cause alarm in patients and their parents. Acrocyanosis typically presents as symmetrical blue and/or purple discoloration in the peripheral extremities, usually either the hands or the feet (Figs 1, 2, 3, 4). In infants, acrocyanosis also includes the perioral area but not the lips or tongue, where central cyanosis becomes a concern. It is often seen after bathing, after feeding, or in a cool environment. It is evanescent and benign. The bluish discoloration in acrocyanosis is often asymptomatic, without clear demarcation of color change. Acrocyanosis episodes can be either precipitated or exacerbated by external factors, such as cold temperatures. Acrocyanosis may also be a process secondary to an underlying systemic disease or a side effect of certain medications. Figure 1. Teenage …

In pediatric patients with anxiety disorders, existing symptom inventories are either not freely available or require extensive time and effort to administer. We sought to evaluate a brief self-report scale-the Generalized Anxiety Disorder 7-item scale (GAD-7)-in adolescents with generalized anxiety disorder (GAD).The Pediatric Anxiety Rating Scale (PARS) and the GAD-7 were administered to youth with GAD (confirmed by structured interview). Relationships between the measures were assessed, and sensitivity and specificity was determined with regard to a global symptom severity measure (Clinical Global Impression-Severity).In adolescents with GAD (N = 40; mean age, 14.8 ± 2.8), PARS and GAD-7 scores strongly correlated (R = 0.65, P ≤ .001) and a main effect for symptom severity was observed (P ≤ .001). GAD-7 scores ≥11 and ≥17 represented the optimum specificity and sensitivity for detecting moderate and severe anxiety, respectively.The PARS and GAD-7 similarly reflect symptom severity. The GAD-7 is associated with acceptable specificity and sensitivity for detecting clinically significant anxiety symptoms. GAD-7 scores may be used to assess anxiety symptoms and to differentiate between mild and moderate GAD in adolescents, and may be more efficient than the PARS.

Pathologic changes to the biceps tendon including subluxation are frequently encountered in patients with subscapularis tears. Operatively managing these combined lesions can be difficult depending on the status of the subscapularis tendon and the degree of biceps medialization. The presented technique is an effective and relatively simple method that simultaneously and efficiently provides for secure tenodesis of the biceps and fixation of subscapularis tendon detachment.

Background The neurophysiological substrates of cognition and emotion, as seen with fMRI, are generally explained using modular structures. The present study was designed to probe the modular structure of cognitive-emotional processing in bipolar and healthy individuals using factor analysis and compare the results with current conceptions of the neurophysiology of bipolar disorder. Methods Exploratory factor analysis was used to assess patterns of covariation among brain regions-of-interest activated during the Continuous Performance Task with Emotional and Neutral Distractors in healthy and bipolar individuals without a priori constraints on the number or composition of latent factors. Results Results indicated a common cognitive-emotional network consisting of prefrontal, medial temporal, limbic, parietal, anterior cingulate and posterior cingulate modules. However, reduced brain activation to emotional stimuli in the frontal, medial temporal and limbic modules was apparent in the bipolar relative to the healthy group, potentially accounting for emotional dysregulation in bipolar disorder. Limitations This study is limited by a relatively small sample size recruited at a single site. The results have yet to be validated on a larger independent sample. Conclusions Although the modular structure of cognitive-emotional processing is similar in bipolar and healthy individuals, activation in response to emotional/neutral cues varies. These findings are not only consistent with recent conceptions of mood regulation in bipolar disorder, but also suggest that regional activation can be considered within tighter modular structures without compromising data interpretation. This demonstration may serve as a template for data reduction in future region-of-interest analyses to increase statistical power.

Early treatment with ACE inhibitors of even moderate heart failure is clinically beneficial, even though haemodynamic measurements cannot adequately quantitate such improvement. Neurohumoral assessment is, however, supposed to be more accurate. In 55 patients with moderate heart failure (ejection fraction < or = 35%), we investigated the dose-dependent effects of ACE inhibition with quinapril taken orally (2.5, 5 or 10 mg b.i.d.) following a placebo-controlled, parallel design protocol over 12 weeks. Plasma components of the renin angiotensin system, catecholamines and ANF were measured together with haemodynamics both at rest and during exercise. Before ACE inhibitor treatment, median PRA, Ang I and II and catecholamines were normal, while ANF was increased. All these parameters, including ACE activity, rose during exercise. Chronic inhibition of ACE activity was dose-dependent and the maximal fall in Ang II occurred with quinapril 20 mg.day-1. Humoral changes appeared more assessible than haemodynamic alterations even though many of these changes were reasonably correlated. The effects of chronic ACE inhibition on circulating neurohumoral components in patients with moderate heart failure are small and dose-dependent. Since humoral changes are related to haemodynamics they should account for the clinical benefit. Appropriately high doses of ACE inhibitors should be chosen for treatment of heart failure.

Objectives Individualized treatment for bipolar disorder based on neuroimaging treatment targets remains elusive. To address this shortcoming, we developed a linguistic machine learning system based on a cascading genetic fuzzy tree (GFT) design called the LITHium Intelligent Agent (LITHIA). Using multiple objectively defined functional magnetic resonance imaging (fMRI) and proton magnetic resonance spectroscopy (1H-MRS) inputs, we tested whether LITHIA could accurately predict the lithium response in participants with first-episode bipolar mania. Methods We identified 20 subjects with first-episode bipolar mania who received an adequate trial of lithium over 8 weeks and both fMRI and 1H-MRS scans at baseline pre-treatment. We trained LITHIA using 18 1H-MRS and 90 fMRI inputs over four training runs to classify treatment response and predict symptom reductions. Each training run contained a randomly selected 80% of the total sample and was followed by a 20% validation run. Over a different randomly selected distribution of the sample, we then compared LITHIA to eight common classification methods. Results LITHIA demonstrated nearly perfect classification accuracy and was able to predict post-treatment symptom reductions at 8 weeks with at least 88% accuracy in training and 80% accuracy in validation. Moreover, LITHIA exceeded the predictive capacity of the eight comparator methods and showed little tendency towards overfitting. Conclusions The results provided proof-of-concept that a novel GFT is capable of providing control to a multidimensional bioinformatics problem—namely, prediction of the lithium response—in a pilot data set. Future work on this, and similar machine learning systems, could help assign psychiatric treatments more efficiently, thereby optimizing outcomes and limiting unnecessary treatment.

Objectives Specific demographic and illness characteristics have been identified as predictors of overall morbidity and treatment course among individuals with bipolar disorder. However, the role of specific cognitive limitations on disease severity and treatment response is unclear. The present study evaluated whether impulsiveness during acute mania was a significant predictor of achieving euthymia within one year following psychiatric hospitalization. Methods Participants were 94 adult inpatients (60 manic) with bipolar I disorder. Baseline symptom severity was assessed using the Young Mania Rating Scale and the Montgomery–Asberg Depression Rating Scale. Impulsivity was measured with the Stop Signal Task, Degraded Stimulus Continuous Performance Task, Delayed Response Task, and Barratt Impulsiveness Scale-11. Results Individual predictors of time to reach euthymia included fewer depressive symptoms and better impulse control at baseline, later age at illness onset, shorter illness duration, and the absence of comorbid attention-deficit hyperactivity disorder. Self-reported impulsivity was a significant independent predictor of time to euthymia, even after accounting for relevant clinical variables. Conclusions Better trait impulse control may be associated with better treatment responsiveness among adults with bipolar disorder.

Bipolar disorder is a highly heritable illness, with genetic influences explaining 60–85% of risk variance (1). However, specific susceptibility genes or neurobiological markers remain unknown. In recent years, genetic and behavioral neuroscience has attempted to define endophenotypes that encompass deficits that are heritable, state-independent, and cosegregated with illness, as well as those which occur at higher rates in unaffected relatives than the general population (2, 3). Plausible endophenotype candidates in bipolar disorder include impairments in specific neurocognitive domains. Cognitive impairments in individuals with bipolar disorder were traditionally thought of as mild and limited to acute mood episodes; however, a growing body of evidence challenges this assumption. At least three recent meta-analyses in euthymic adults with bipolar disorder (4–6) and two in youths with bipolar disorder have identified several cognitive impairments, particularly in attention, processing speed, and other aspects of executive function (7, 8). Some studies have suggested that medication exposure has an effect on cognition in both adult (9) and pediatric bipolar disorder subjects (10), while others have suggested no neurocognitive differences in euthymic unmedicated pediatric bipolar disorder subjects (11). Thus, studies of cognitive impairment in youths and adults with bipolar disorder cannot fully dissociate possible effects of illness chronicity and medication exposure. Studying youth at familial risk for developing bipolar disorder (i.e., with a parent who has bipolar disorder) could facilitate identifying cognitive endophenotypes, yet few studies have examined neurocognitive function in this population. Nonetheless, recent studies suggest that children of bipolar disorder patients demonstrate specific deficits in executive function, particularly in tasks assessing cognitive interference and flexibility (12, 13). Cognitive interference occurs when task-irrelevant background information impedes processing task-relevant information that forms the current focus of attention (14). Cognitive conflict may be best described as a special instance of cognitive interference in which task-irrelevant information induces incongruent or incompatible mental representations (15). Given this theoretical approach, selecting task-relevant over task-irrelevant information may be thought of as a core process in the resolution of cognitive interference, and the main goal of conflict monitoring (16). Similarly, changes in processing speed with shifting levels of conflict represent a measure of conflict-driven adaptation (17). In the current study, we examined conflict monitoring and conflict-driven adaptation in youths at risk for bipolar disorder using an arrow version of the Eriksen Flanker Task (EFT). We hypothesized that youths at risk for bipolar disorder would exhibit deficits in conflict monitoring and conflict-driven adaptation. Additionally, we predicted that youths at risk for developing bipolar disorder would be more susceptible to interference, exhibit increased behavioral inconsistencies as measured by increased variability of response time, and show less flexible cognitive adaptation to shifting levels of conflict than healthy controls.