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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.

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

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 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.

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.

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.

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

Homologous series are layered phases that can have a range of stoichiometries depending on an index n. Examples of perovskite-related homologous series include (ABO3)nAO Ruddlesden–Popper phases and (Bi2O2) (An−1BnO3n+1) Aurivillius phases. It is challenging to precisely control n because other members of the homologous series have similar stoichiometry and a phase with the desired n is degenerate in energy with syntactic intergrowths among similar n values; this challenge is amplified as n increases. To improve the ability to synthesize a targeted phase with precise control of the atomic layering, we apply the x-ray diffraction (XRD) approach developed for superlattices of III–V semiconductors to measure minute deviations from the ideal structure so that they can be quantitatively eradicated in subsequent films. We demonstrate the precision of this approach by improving the growth of known Ruddlesden–Popper phases and ultimately, by synthesizing an unprecedented n = 20 Ruddlesden–Popper phase, (ATiO3)20AO where the A-site occupancy is Ba0.6Sr0.4. We demonstrate the generality of this method by applying it to Aurivillius phases and the Bi2Sr2Can–1CunO2n+4 series of high-temperature superconducting phases.

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.

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.

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.

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.

This article describes bench scale sequential, biological and coagulation-flocculation treatment of mature leachate for the removal of nitrogen and biodegradable and recalcitrant carbonaceous material. The biological stage was conducted on two SBRs, one of which inoculated with nitrifying sludge, another without an inoculum, for 152 and 133 days, respectively. The coagulation-flocculation stage used four coagulants at different doses and pH adjustments. The treatment conducted on the inoculated SBR when a pH control was used produced mean removals of BOD5, COD and TKN of 69.6%, 38.5% and 51.6%, respectively, and practically complete denitrification. Coagulation-flocculation applied to the effluent of the inoculated biological reactor showed a superior effectiveness of the ferric coagulants, when the pH was adjusted to close to 6.0, producing removals of turbidity, COD and true color close to 95%, 78% and 92%, respectively.

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.

The purpose of this study was to explore the correlates of online health information-seeking behaviors among Hispanic residents of a low-income urban neighborhood.Data were collected with a community survey from 1045 unique participants at ambulatory care clinics in a largely Hispanic immigrant community in northern Manhattan, New York. A descriptive correlational analysis was conducted using logistic regression.A majority of the participants were born outside the United States (85.7%), and half (50.3%) had completed high school. A logistic regression revealed that five independent variables were significantly correlated with online health information-seeking behaviors: age, education, marital status, primary language, and health literacy. Age and Spanish as preferred language were negatively associated with online health information-seeking (OR = 0.93 and 0.50), whereas education and health literacy were positively associated with online health information-seeking (OR = 4.28 and 1.28).The findings have implications for designing online health information resources and interventions appropriate for the populations they are likely to reach. Furthermore, the findings highlight the need for special efforts to ensure access to reliable health information for immigrant populations and those with low health literacy.

Heffner JL, Fleck DE, DelBello MP, Adler CM, Strakowski SM. Cigarette smoking and impulsivity in bipolar disorder. Bipolar Disord 2012: 14: 735–742. © 2012 The Authors. Journal compilation © 2012 John Wiley & Sons A/S. Objectives: There is a high prevalence of smoking among individuals with bipolar disorder, yet there have been few efforts to identify potential contributing factors as a means of improving prevention and treatment approaches. The goal of this study was to examine the association between impulsivity and the initiation or maintenance of smoking in bipolar disorder. Methods: Participants comprised 97 adolescents and adults, ages 16–50, with bipolar I disorder who were experiencing a mixed or manic episode at the time of study enrollment. Participants completed the Barratt Impulsiveness Scale-11 (BIS-11) as a self-report indicator of trait impulsivity, and the Logan Stop-Signal Task (SST), Delayed Reward Task (DRT), and Degraded Stimulus Continuous Performance Task (DSCPT) as behavioral measures of impulsivity. Results: Current smokers (34%) and former smokers (23%) generally reported higher trait impulsivity on the BIS-11 than never smokers (43%), with minimal evidence for differences among the two ever-smoking groups. No differences in impulsivity by smoking status emerged on the behavioral measures. Conclusions: Trait impulsivity is associated with the initiation, but not necessarily the maintenance, of cigarette smoking in adolescents and adults with bipolar disorder. Our findings provide no evidence that smoking is associated with impulsive responding on cognitive tasks during a symptomatic period during which impulsivity is elevated.

Bipolar I disorder is defined by the occurrence of mania and exhibits a dynamic course of symptoms that alternate among affective extremes. The specific neurophysiological basis of bipolar disorder is unknown, but neuroimaging studies suggest impairments in corticolimbic regions responsible for regulating emotion that have been termed the anterior limbic network (1–5). In subjects with bipolar I disorder, abnormal brain activation has been shown in the amygdala, anterior cingulate gyrus (ACC), ventrolateral prefrontal cortex (VLPFC), insula, and medial prefrontal cortex (1, 3). The amygdala seems to play a central role in this network and is responsible for the appraisal of emotional stimuli (6–8). Other regions in the anterior limbic network, including the VLPFC and insula, interact with the amygdala to provide cortical modulation of the appraisal process (3). Patients with bipolar I disorder spend significantly more time in depression than mania (9). Yet few studies have specifically examined the neurophysiology of the depressed phase of bipolar I disorder, and it is not clear which corticolimbic regions are involved in the generation of the syndrome of depression or involved in the switch from mania to depression. One approach to answer these questions is to use imaging to examine patients with bipolar I disorder across different mood states. However, there are few longitudinal imaging studies of bipolar I disorder across mood states (3). Comparing the same patients across manic and depressive episodes may lead to a better understanding of the how corticolimbic networks generate mood states (10). The current study was designed to understand the role of the amygdala during the course of bipolar I disorder. Using amygdala as the primary seed region in a functional connectivity analysis allowed us to identify altered connections with other brain regions in mania and depression. Subjects with bipolar I disorder were assessed during an initial manic or mixed episode and then followed for up to one year and re-assessed if they developed a depressive episode. Subjects received an fMRI scan at each assessment while performing a modified continuous performance task with emotional distracters (5). The task was designed to discriminate between ventral emotional and dorsal cognitive brain networks and their interaction and requires effective regulation of emotion to complete successfully (5). We predicted that subjects with bipolar I disorder would show different patterns of amygdala connectivity in mania versus depression. Given previous findings of decreased prefrontal modulation of limbic regions in mania, we predicted that when subjects no longer had manic symptoms (i.e., they switched to being in a depressive episode) activation in these brain regions would normalize to more closely resemble healthy comparison subjects (HC) (5, 11–13). Therefore we predicted that during depression subjects would show increased amygdala connectivity with ventral and dorsal prefrontal regions.

Objectives Cigarette smoking is highly prevalent among individuals with bipolar disorder (BD) and may adversely affect symptoms of the disorder as well as co-occurrence of other substance use disorders. However, anecdotal reports suggesting that smoking cessation caused a worsening of mood in smokers with BD have raised concerns about quitting. In this study, we prospectively evaluated the course of BD, alcohol use disorders, and cannabis use disorders in relation to smoking and examined the relationship between smoking abstinence and changes in mood.

Treating septic arthritis of the hip with coexisting advanced degenerative disease is challenging. The use of primary total hip arthroplasty (THA) has led to postoperative infection rates as high as 22%. Insertion of antibiotic spacers with subsequent reimplantation of a THA controls infection and improves pain and function in patients with periprosthetic infections.We asked whether two-stage exchange for patients with degenerative joint disease (DJD) and coexisting septic arthritis would control infection and improve pain relief and function both during the period after insertion of the spacer and after conversion to THA.We retrospectively reviewed 14 patients with severe DJD and either active or recent septic arthritis treated with débridement and insertion of a primary antibiotic-loaded cement spacer between 1996 and 2008. Ten patients underwent subsequent exchange to a permanent hip arthroplasty. Four patients did not undergo exchange to a permanent THA: two died from unrelated causes and two elected not to proceed with exchange because their spacer provided adequate function. We obtained a modified Harris hip score. The minimum clinical followup was 7 months (average, 28 months; range, 7-65 months) after insertion of the spacer.Mean pain scores improved from 6 to 34, and overall Harris hip scores improved from 11 to 67 at last followup with the spacer. Those who underwent definitive THA had further improvement in their mean Harris hip scores to 93.Articulating antibiotic spacers offer acceptable pain relief and function while the infection is treated in this unique group of patients.Level IV, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.

To compare the type and degree of impulsivity among adolescents with bipolar disorder (BD), adolescents with attention-deficit/hyperactivity disorder (ADHD), and healthy comparison subjects using the Barratt Impulsiveness Scale, Version 11 (BIS-11).Manic adolescents with BD (n=31), adolescents with ADHD (n=30), and healthy subjects (n=25) completed the BIS-11, a 30-item, self-report scale with three subscales (cognitive, motor, and nonplanning). The BIS-11 total and subscale scores were compared among groups. We also examined associations among the BIS-11, Young Mania Rating Scale and co-occurring disruptive behavioral disorders (DBDs) within the BD group.Total and each subscale scores were significantly higher for the BD group than for the healthy controls (p0.05). The total scores and the cognitive and motor subscale scores were significantly higher for the ADHD group than for the healthy control group (p0.05). However, there was no statistically significant difference between the nonplanning subscale scores of the ADHD group and the healthy control group (p0.05). There were no significant differences between the BD and ADHD groups or between the BD groups with and without ADHD. The BD patients with DBDs (i.e., oppositional defiant disorder or conduct disorder) scored significantly higher on the motor subscale than did BD patients without DBDs. There were no statistically significant associations between the Young Mania Rating Scale and BIS-11 scores within the BD group.Our findings suggest that impulsivity is elevated in adolescents with BD as well as adolescents with ADHD, except for nonplanning impulsivity, which was not significantly different between adolescents with ADHD and the healthy comparison group. This may suggest that nonplanning impulsivity is relatively specific to adolescents with BD. Additionally, our data indicate that elevations in impulsivity, as measured by the BIS-11, may be independent of symptoms severity and, therefore, may be a stable, trait-related component of BD.

We examined sustained attention deficits in bipolar disorder and associated changes in brain activation assessed by functional magnetic resonance imaging (fMRI). We hypothesized that relative to healthy participants, those with mania or mixed mania would (1) exhibit incremental decrements in sustained attention over time, (2) overactivate brain regions required for emotional processing and (3) progressively underactivate attentional regions of prefrontal cortex. Fifty participants with manic/mixed bipolar disorder (BP group) and 34 healthy comparison subjects (HC group) received an fMRI scan while performing a 15-min continuous performance task (CPT). The data were divided into three consecutive 5-min vigilance periods to analyze sustained attention. Composite brain activation maps indicated that both groups activated dorsal and ventral regions of an anterior-limbic network, but the BP group exhibited less activation over time relative to baseline. Consistent with hypotheses 1 and 2, the BP group showed a marginally greater behavioral CPT sustained attention decrement and more bilateral amygdala activation than the HC group, respectively. Instead of differential activation in prefrontal cortex over time, as predicted in hypothesis 3, the BP group progressively decreased activation in subcortical regions of striatum and thalamus relative to the HC group. These results suggest that regional activation decrements in dorsolateral prefrontal cortex accompany sustained attention decrements in both bipolar and healthy individuals. Stable amygdala overactivation across prolonged vigils may interfere with sustained attention and exacerbate attentional deficits in bipolar disorder. Differential striatal and thalamic deactivation in bipolar disorder is interpreted as a loss of amygdala (emotional brain) modulation by the ventrolateral prefrontal-subcortical circuit, which interferes with attentional maintenance.

Impulsivity is a frequent component of the course and presentation of bipolar disorder; it has therefore been proposed to represent a core feature of the illness that persists across different affective states (1–8). However, impulsivity is a multi-faceted construct that cannot be defined by a single behavior. For example, based on studies with the Barratt Impulsiveness Scale (BIS), Barratt and colleagues suggested that impulsivity consists of three independent behavioral factors (9,10). These factors include: 1) Non-planning Impulsiveness, which refers to a present orientation or failure to consider the future; 2) Motor Impulsiveness, i.e., acting without thinking; and 3) Attentional Impulsiveness, which is a tendency to shift attention quickly, causing inappropriately rapid decisions. This work and that of others (e.g., 11–13) suggests that impulsivity is comprised of three components: 1) an inability to delay gratification, i.e., an inability to delay response for an immediate reward in order to gain a larger reward or prevent a negative consequence; 2) disinhibition, i.e., an inability to inhibit a prepotent response in favor of a better response; and 3) inattention, i.e., an inability to maintain attention to complete a particular task rather than being distracted to an alternative task (4). These three behavioral components of impulsivity appear to be independent and may be mediated by semi-independent neural systems (12). We recently examined these three aspects of impulsivity during the manic phase of bipolar disorder (4). In order to assess these behaviors we employed a stop-signal task, delayed reward task, and a continuous performance task, respectively. We found that these three aspects of impulsivity were largely independent, were elevated in mania as compared with healthy subjects, and did not correlate with affective symptoms (4). These findings supported the proposal that impulsivity may represent a core trait of bipolar disorder that is independent of symptom severity (1–4). However, we also found that manic patients were more impulsive on the delayed reward task than mixed patients (4), suggesting that impulsivity may instead be related to affective state. In the absence of longitudinal measures within individual subjects, we could not resolve this apparent contradiction. Moreover, to our knowledge, no previous studies have longitudinally examined impulsivity in bipolar disorder, leaving the state or trait nature of these behaviors uncertain. With these considerations in mind, the aim of the present study was to determine whether impulsivity observed during mania persists across phases of bipolar illness, in order to clarify whether impulsivity is independent of affective state. To achieve this aim, we administered the previously described tasks (4) and the Barratt Impulsiveness Scale (BIS-11)(9) to 108 bipolar subjects during an acute manic or mixed episode and then again as these subjects developed depression and achieved euthymia. We predicted that elevated ratings on the BIS-11 and impulsive responding on the behavioral tasks would longitudinally persist during depression and euthymia, consistent with the hypothesis that impulsivity is core trait of bipolar disorder.

Aim: To identify differential patterns of brain activation between adolescents with bipolar disorder and adolescents with attention-deficit hyperactivity disorder (ADHD) to better understand the neurophysiology of both disorders. We hypothesized that subjects with ADHD would show altered activation in brain regions involved in executive and sustained attention. In contrast, we hypothesized that bipolar subjects would show altered brain activation in regions responsible for emotionally homeostasis, including the striatum and amygdala. Methods: Functional magnetic resonance imaging was performed during a continuous performance task with a response inhibition component in 11 adolescents with bipolar disorder during a manic episode, 10 adolescents with ADHD, and 13 healthy adolescents. Results: There were no differences in behavioural performance among the three groups. Compared with bipolar subjects, subjects with ADHD showed increased activation in the superior temporal lobe during successful response inhibition. Although bipolar subjects did not show activation differences in the striatum or amygdala compared with ADHD subjects, increased left parahippocampal activation in the bipolar group was associated with increased manic symptoms. Conclusions: The patterns of brain activation observed in the current study support divergent patterns of neurophysiological dysfunction in individuals with bipolar disorder as compared with those with ADHD. Therefore, the impulsive behaviour seen in both disorders may be the consequence of dysfunction in different brain regions, and further research may help identify neurobiological markers that are specific to each condition.

Objective: To determine whether specific aspects of impulsivity (response disinhibition, inability to delay gratification, inattention) differ between healthy and bipolar manic subjects, and whether these aspects of impulsivity were associated with each other and severity of affective symptoms. Methods: Performance of 70 bipolar I manic or mixed patients was compared to that of 34 healthy subjects on three tasks specifically designed to study response inhibition, ability to delay gratification, and attention; namely, a stop signal task, a delayed reward task, and a continuous performance task, respectively. Correlations among tasks and with symptom ratings were also performed. Results: Bipolar subjects demonstrated significant deficits on all three tasks as compared to healthy subjects. Performance on the three tasks was largely independent. Task performance was not significantly associated with the severity of affective symptom ratings. However, measures of response inhibition and attention were sensitive to medication effects. Differences in the delayed reward task were independent of medication effects or symptom ratings. During the delayed reward task, although bipolar patients made their choices more slowly than healthy subjects, they were significantly more likely to choose a smaller, but more quickly obtained reward. Moreover, performance on this task was not associated with performance on the other impulsivity measures. Manic patients showed more impulsive responding than mixed patients. Conclusions: Bipolar I manic patients demonstrate deficits on tests of various aspects of impulsivity as compared to healthy subjects. Some of these differences between groups may be mediated by medication effects. Findings suggested that inability to delay gratification (i.e., delayed reward task) was not simply a result of the speed of decision making or inattention, but rather that it reflected differences between bipolar and healthy subjects in the valuation of reward relative to delay.

Aims: Impulsivity is common in bipolar disorder, especially during mania. Understanding the functional neuroanatomy of response inhibition, one component of impulsivity, might clarify the neural substrate of bipolar disorder. Methods: Sixteen DSM-IV first-episode, manic bipolar patients and 16 matched healthy subjects were examined during a first manic episode using functional magnetic resonance imaging while performing a response inhibition task. All subjects were studied using a 4.0 Tesla Varian Unity INOVA Whole Body MRI/MRS system. The response inhibition task was presented using non-ferromagnetic goggles, and task performance was recorded during scan acquisition. Imaging data were analysed using analysis of functional neuroimages. Group contrasts were made for the specific response inhibition measure. Results: The groups performed the task similarly, although both demonstrated relatively poor rates of target response, but high rates of successful ‘stops’. Despite similar behavioural results, the groups showed significantly different patterns of functional magnetic resonance imaging brain activation. Specifically, during response inhibition, the healthy subjects exhibited significantly greater activation in anterior and posterior cingulate, medial dorsal thalamus, middle temporal gyrus, and precuneus. The bipolar patients exhibited prefrontal activation (BA 10) that was not observed in healthy subjects. Conclusions: Bipolar and healthy subjects exhibit different patterns of brain activation to response inhibition; these differences may reflect different functional neuroanatomic approaches to response inhibition between the two groups.

Previous research has shown that performance on cognitive tasks administered in the scanner can be altered by the scanner environment. There are no previous studies that have investigated the impact of scanner noise using a well-validated measure of affective change. The goal of this study was to determine whether performance on an affective attentional task or emotional response to the task would change in the presence of distracting acoustic noise, such as that encountered in a magnetic resonance imaging (MRI) environment.Thirty-four young adults with no self-reported history of neurologic disorder or mental illness completed three blocks of the affective Posner task outside of the scanner. The task was meant to induce frustration through monetary contingencies and rigged feedback. Participants completed a Self-Assessment Manikin at the end of each block to rate their mood, arousal level, and sense of dominance. During the task, half of the participants heard noise (recorded from a 4T MRI system), and half heard no noise.The affective Posner task led to significant reductions in mood and increases in arousal in healthy participants. The presence of scanner noise did not impact task performance; however, individuals in the noise group did report significantly poorer mood throughout the task.The results of the present study suggest that the acoustic qualities of MRI enhance frustration effects on an affective attentional task and that scanner noise may influence mood during similar functional magnetic resonance imaging (fMRI) tasks.

The present study was conducted to determine the pattern of incorporation of dietary EPA and docosahexaenoic acid (DHA) into milk, and to evaluate consequent changes in milk fat composition and sensory characteristics. Fourteen multiparous cows in early lactation were divided into two groups and were offered supplements for 10 d. While individual stalls after each morning milking, one group was offered a mixture of rumen-protected tuna oil (RPTO)–soyabean supplement (2 kg; 30:70, w/w; +RPTO) and the second group was offered the basal ration without RPTO (−RPTO). Both groups grazed together on a spring pasture after supplementation. Feeding supplemental RPTO increased the concentrations of EPA and DHA in milk fat from undetectable levels in −RPTO cows to 6·9 and 10·1 g/kg milk fat respectively. Total n-3 PUFA concentration in milk fat was increased three- to fourfold by tuna-oil supplementation (8·4 to 32·0 g/kg milk fat). There were no significant effects on milk production (35·4 v. 33·9 l/d), milk protein (28·2 v. 30·1 g/kg) or milk fat (36·2 v. 40·4 g/kg for −RPTO and +RPTO respectively). The concentration of total saturated fatty acids in milk fat was significantly reduced (568 v. 520 g/kg total fatty acids) and there was a 17 % reduction in the atherosclerotic index of milk after tuna-oil supplementation. Untrained consumer panellists (n 61) rated milk from both groups of cows similarly for taste and smell. We conclude that it is possible to enrich milk with n-3 PUFA without deleterious effects on yield, milk composition or sensory characteristics.

The effects of diets high inn-3 polyunsaturated fatty acids (PUFA; provided by fish oil),n-6 PUFA (sunflower oil) or in more-saturated fatty acids (tallow) on the distribution of subclasses of choline phospholipids (PC) and ethanolamine phospholipids (PE) from the breast muscle of broiler chickens were examined. Supplementation with the different fatty acids had no effect on the distribution of phospholipid subclasses. Feeding sunflower oil or tallow gave a molecular-species profile similar in both fatty acid subtype and proportion. In the diacyl PC phospholipids, 16: 0–18: 1n-9 and 16: 0–18: 2n-6 accounted for approximately 60 % of the total molecular species, whereas for the alkylenyl PC the predominant species were 16: 0–18: 1n-9 and 16: 0–20: 4n-6. Of the diacyl PE the dominant species was 18: 0–20: 4n-6 which accounted for 50 % of the molecular species, and of the alkylenyl PE the dominant species were 16: 0–18: 1n-9, 16: 0–20: 4n-6 and 18: 0–20: 4n-6. Supplementation with fish oil significantly increased levels of both eicosapentaenoic acid (20: 5n-3) and docosahexaenoic acid (22: 6n-3) in PC and PE when compared with either sunflower oil or tallow supplementation. The increase in then-3 PUFA incorporation was associated with a corresponding decrease in the proportion of arachidonic acid (20: 4n-6) in both PC and PE. Different dietary fats induce different patterns of fatty acid incorporation and substitution in thesn-2 position of the diacyl and alkylenyl PC and PE of avian breast muscle, and this finding is indicative of selective acyl remodelling in these two phospholipids.

The effects of dietary saturated fatty acids and polyunsaturated fatty acids (PUFA) of then-3 andn-6 series on weight gain, body composition and substrate oxidation were investigated in broiler chickens. At 3 weeks of age three groups of chickens (n30; ten birds per group) were fed the fat-enriched experimental diets for 5 weeks. These diets were isonitrogenous, isoenergetic and contained 208 g protein/kg and 80 g edible tallow, fish oil or sunflower oil/kg; the dietary fatty acid profiles were thus dominated by saturated fatty acids,n-3 PUFA orn-6 PUFA respectively. Resting RQ was measured in five birds from each treatment group during weeks 4 and 5 of the experiment. There were no significant differences between treatments in total feed intake or final body mass. Birds fed the PUFA diets had lower RQ and significantly reduced abdominal fat pad weights (PPn-3 andn-6 PUFA groups). In addition, the PUFA-rich diets lowered plasma concentrations of serum triacylglycerols and cholesterol. The findings indicate that dietary fatty acid profile influences nutrient partitioning in broiler chickens.

Reports of normal Continuous Performance Test (CPT) accuracy in patients with temporal lobe epilepsy (TLE) stand in contrast to a demonstration of nonspecific absolute reaction time (RT) deficits in this population. In this study, we examined CPT data from a TLE sample for potential RT deficits across three consecutive blocks of time during the vigil. Seventeen patients with medically intractable epilepsy of temporal lobe origin and 17 healthy volunteers participated. The Conners CPT was used to assess sustained attention over a 14-min vigil. There were no significant group differences in accuracy. There was, however, a significant interaction between groups and time intervals, with disproportionate RT increases for patients at the end of the vigil. These findings are consistent with a report of nonspecific RT deficits in TLE despite normal accuracy scores, and further indicate impaired RT performance over time.