BDNF Val66Met polymorphism in patterns of neural activation in individuals with MDD and healthy controls.

BACKGROUND: Rs6265 single nucleotide polymorphism, which influences brain-derived neurotrophic factor (BDNF) levels in the cortical and subcortical brain structures, may result in distinguished patterns of neural activation during a major depressive disorder (MDD) episode. Valine homozygotes with high levels of BDNF and methionine carriers with lower levels of BDNF may present specific neural correlates of MDD. In our study we have tested differences in blood oxygen level dependant (BOLD) signal between individuals with MDD and healthy controls for both allelic variants. METHODS: Individuals with MDD (N = 37) and healthy controls (N = 39) were genotyped for rs6265 and compared separately in each allelic variant for BOLD response in a functional magnetic resonance imaging experiment examining appraisal of emotional scenes. The two allelic variants were also compared separately for both individuals with MDD and healthy controls. RESULTS: In the homozygous valine group MDD was associated with decreased neural activation in areas responsible for cognitive appraisal of emotional scenes. In the methionine group MDD was related to increased activation in subcortical regions responsible for visceral reaction to emotional stimuli. During an MDD episode methionine carriers showed more activation in areas associated with cognitive appraisal of emotional information in comparison to valine homozygotes. LIMITATIONS: Small sample size of healthy controls carrying methionine (N=8). CONCLUSION: Our results suggest that allelic variations in the rs6265 gene lead to specific neural correlates of MDD which may be associated with different mechanisms of MDD in the two allelic groups. This may have potential importance for screening and treatment of patients.Funding for this study was provided by the Science Foundation Ireland (Grant Number: SFI/07SK/B1214C). Health Research Board (HRB) Ireland provided funding for magnetic resonance imaging infrastructure at the Centre of Advanced Medical Imaging (CAMI) at St. James’s Hospital in Dublin.This is the author accepted manuscript. The final version is available from Elsevier at http://www.jad-journal.com/article/S0165-0327%2815%2900383-3/abstract

Negative Experiences in Television Programming : A View from the Other Side

Many professional archaeologists will engage with television. There seems to be little guidance- other than trial and error and personal communications - for navigating interactions with media production companies. Here, through a series of informal questions and answers, I present some issues with which one might be confronted in such engagements. I base my discussions on personal experience, literature, and conversations with experienced colleagues. A key point is that media production companies' agendas and priorities often differ from those of archaeologists. While the article draws on experiences from Europe and North America, it has relevance for archaeologists working with television everywhere.Peer reviewe

Frequency and Severity Approaches to Indexing Exposure to Trauma: The Critical Incident History Questionnaire for Police Officers

The Critical Incident History Questionnaire indexes cumulative exposure to traumatic incidents in police by examining incident frequency and rated severity. In over 700 officers, event severity was negatively correlated (rs = -61) with frequency of exposure. Cumulative exposure indices that varied emphasis on frequency and severity-using both nomothetic and idiographic methods-all showed satisfactory psychometric properties and similar correlates. All indices were only modestly related to posttraumatic stress disorder (PTSD) symptoms. Ratings of incident severity were not influenced by whether officers had ever experienced the incident. Because no index summarizing cumulative exposure to trauma had superior validity, our findings suggest that precision is not increased if frequency is weighted by severity

Impaired reward processing in the human prefrontal cortex distinguishes between persistent and remittent attention deficit hyperactivity disorder

Symptoms of attention deficit hyperactivity disorder (ADHD) in children often persist into adulthood and can lead to severe antisocial behavior. However, to-date it remains unclear whether neuro-functional abnormalities cause ADHD, which in turn can then provide a marker of persistent ADHD. Using event-related functional magnetic resonance imaging (fMRI), we measured blood oxygenation level dependent (BOLD) signal changes in subjects during a reversal learning task in which choice of the correct stimulus led to a probabilistically determined ‘monetary’ reward or punishment. Participants were diagnosed with ADHD during their childhood (N = 32) and were paired with age, gender, and education matched healthy controls (N = 32). Reassessment of the ADHD group as adults resulted in a split between either persistent (persisters, N = 17) or remitted ADHDs (remitters, N = 15). All three groups showed significantly decreased activation in the medial prefrontal cortex (PFC) and the left striatum during punished correct responses, however only remitters and controls presented significant psycho-physiological interaction between these fronto-striatal reward and outcome valence networks. Comparing persisters to remitters and controls showed significantly inverted responses to punishment (P < 0.05, family-wise error corrected) in left PFC region. Interestingly, the decreased activation shown after punishment was located in different areas of the PFC for remitters compared with controls, suggesting that remitters might have learned compensation strategies to overcome their ADHD symptoms. Thus, fMRI helps understanding the neuro-functional basis of ADHD related behavior differences and differentiates between persistent and remittent ADHD

A trigger-substrate model for smiling during an automated formative quiz: engagement is the substrate, not frustration

INTRODUCTION: Automated tutoring systems aim to respond to the learner’s cognitive state in order to maintain engagement. The end-user’s state might be inferred by interactive timings, bodily movements or facial expressions. Problematic computerized stimuli are known to cause smiling during periods of frustration. METHODS: Forty-four seated, healthy participants (age range 18-35, 18 male) used a handheld trackball to answer a computer-presented, formative, 3-way multiple choice geography quiz, with 9 questions, lasting a total of 175 seconds. Frontal facial videos (10 Hz) were collected with a webcam and processed for facial expressions by CrowdEmotion using a pattern recognition algorithm. Interactivity was recorded by a keystroke logger (Inputlog 5.2). Subjective responses were collected immediately after each quiz using a panel of visual analogue scales (VAS). RESULTS: Smiling was fie-fold enriched during the instantaneous feedback segments of the quiz, and this was correlated with VAS ratings for engagement but not with happiness or frustration. Nevertheless, smiling rate was significantly higher after wrong answers compared to correct ones, and frustration was correlated with the number of questions answered incorrectly. CONCLUSION: The apparent disconnect between the increased smiling during incorrect answers but the lack of correlation between VAS frustration and smiles suggests a trigger-substrate model where engagement is the permissive substrate, while the noises made by the quiz after wrong answers may be the trigger

Multiplexed Immunoassay Panel Identifies Novel CSF Biomarkers for Alzheimer's Disease Diagnosis and Prognosis

Clinicopathological studies suggest that Alzheimer's disease (AD) pathology begins ∼10-15 years before the resulting cognitive impairment draws medical attention. Biomarkers that can detect AD pathology in its early stages and predict dementia onset would, therefore, be invaluable for patient care and efficient clinical trial design. We utilized a targeted proteomics approach to discover novel cerebrospinal fluid (CSF) biomarkers that can augment the diagnostic and prognostic accuracy of current leading CSF biomarkers (Aβ42, tau, p-tau181).Using a multiplexed Luminex platform, 190 analytes were measured in 333 CSF samples from cognitively normal (Clinical Dementia Rating [CDR] 0), very mildly demented (CDR 0.5), and mildly demented (CDR 1) individuals. Mean levels of 37 analytes (12 after Bonferroni correction) were found to differ between CDR 0 and CDR>0 groups. Receiver-operating characteristic curve analyses revealed that small combinations of a subset of these markers (cystatin C, VEGF, TRAIL-R3, PAI-1, PP, NT-proBNP, MMP-10, MIF, GRO-α, fibrinogen, FAS, eotaxin-3) enhanced the ability of the best-performing established CSF biomarker, the tau/Aβ42 ratio, to discriminate CDR>0 from CDR 0 individuals. Multiple machine learning algorithms likewise showed that the novel biomarker panels improved the diagnostic performance of the current leading biomarkers. Importantly, most of the markers that best discriminated CDR 0 from CDR>0 individuals in the more targeted ROC analyses were also identified as top predictors in the machine learning models, reconfirming their potential as biomarkers for early-stage AD. Cox proportional hazards models demonstrated that an optimal panel of markers for predicting risk of developing cognitive impairment (CDR 0 to CDR>0 conversion) consisted of calbindin, Aβ42, and age.Using a targeted proteomic screen, we identified novel candidate biomarkers that complement the best current CSF biomarkers for distinguishing very mildly/mildly demented from cognitively normal individuals. Additionally, we identified a novel biomarker (calbindin) with significant prognostic potential

NHC-catalysed aerobic aldehyde-esterifications with alcohols: no additives or cocatalysts required

A highly efficient, broad scope, additive-free mild protocol for the oxidative carbene-catalysed esterification of aldehydes (including the related aqueous oxidation to acids) has been developed

Household Effects of School Closure during Pandemic (H1N1) 2009, Pennsylvania, USA

To determine the effects of school closure, we surveyed 214 households after a 1-week elementary school closure because of pandemic (H1N1) 2009. Students spent 77% of the closure days at home, 69% of students visited at least 1 other location, and 79% of households reported that adults missed no days of work to watch children