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WUSTL Neuroscience Publications Archive - January 2013

January 31, 2013

Zazulia, A.R.a , Diringer, M.N.b
Acute Stroke Care
(2012) Critical Care, 17 (1), art. no. 301, . 

a Vascular Neurology, Department of Neurology, Washington University School of Medicine, Saint Louis, MO 63110, United States
b Neurocritical Care Section, Department of Neurology, Washington University School of Medicine, Saint Louis, MO 63110, United States

Abstract
Ken Uchino, Jennifer Pary, James Grotta: Acute Stroke Care. 2nd edition. Cambridge University Press, 2011, 234 pp., ISBN-13: 978-0521184847. © 2013 BioMed Central Ltd.

Document Type: Article
Source: Scopus

Hill, K.K.a , Campbell, M.C.b c , McNeely, M.E.d , Karimi, M.b , Ushe, M.b , Tabbal, S.D.b , Hershey, T.b c e , Flores, H.P.b , Hartlein, J.M.b , Lugar, H.M.e , Revilla, F.J.f , Videen, T.O.b c , Earhart, G.M.b d g , Perlmutter, J.S.b c d g h
Cerebral blood flow responses to dorsal and ventral STN DBS correlate with gait and balance responses in Parkinson's disease
(2013) Experimental Neurology, 241 (1), pp. 105-112. 

a Department of Biomedical Engineering, Washington University School of Medicine, St. Louis, MO, United States
b Department of Neurology, Washington University School of Medicine, St. Louis, MO, United States
c Department of Radiology, Washington University School of Medicine, St. Louis, MO, United States
d Program in Physical Therapy, Washington University School of Medicine, St. Louis, MO, United States
e Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, United States
f Department of Neurology, University of Cincinnati, Cincinnati, OH, United States
g Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, MO, United States
h Program in Occupational Therapy, Washington University School of Medicine, St. Louis, MO, United States

Abstract
Objectives: The effects of subthalamic nucleus (STN) deep brain stimulation (DBS) on gait and balance vary and the underlying mechanisms remain unclear. DBS location may alter motor benefit due to anatomical heterogeneity in STN. The purposes of this study were to (1) compare the effects of DBS of dorsal (D-STN) versus ventral (V-STN) regions on gait, balance and regional cerebral blood flow (rCBF) and (2) examine the relationships between changes in rCBF and changes in gait and balance induced by D-STN or V-STN DBS. Methods: We used a validated atlas registration to locate and stimulate through electrode contacts in D-STN and V-STN regions of 37 people with Parkinson's disease. In a within-subjects, double-blind and counterbalanced design controlled for DBS settings, we measured PET rCBF responses in a priori regions of interest and quantified gait and balance during DBS Off, unilateral D-STN DBS and unilateral V-STN DBS. Results: DBS of either site increased stride length without producing significant group-level changes in gait velocity, cadence or balance. Both sites increased rCBF in subcortical regions and produced variable changes in cortical and cerebellar regions. DBS-induced changes in gait velocity are related to premotor cortex rCBF changes during V-STN DBS (r=. - 0.40, p=. 0.03) and to rCBF changes in the cerebellum anterior lobe during D-STN DBS (r=. - 0.43, p=. 0.02). Conclusions: DBS-induced changes in gait corresponded to rCBF responses in selected cortical and cerebellar regions. These relationships differed during D-STN versus V-STN DBS, suggesting DBS acts through distinct neuronal pathways dependent on DBS location. © 2012 Elsevier Inc.

Author Keywords
Deep brain stimulation;  Gait;  Parkinson's disease;  Positron emission tomography;  Subthalamic nucleus

Document Type: Article
Source: Scopus

Yoon, C.W.a , Seo, S.W.a , Park, J.-S.b , Kwak, K.-C.b , Yoon, U.c , Suh, M.K.a , Kim, G.H.a , Shin, J.S.a , Kim, C.H.a , Noh, Y.a , Cho, H.a , Kim, M.-J.d , Kim, J.H.e , Roh, J.H.f , Lee, J.-M.b , Na, D.L.a
Cerebellar atrophy in patients with subcortical-type vascular cognitive impairment
(2013) Cerebellum, 12 (1), pp. 35-42. 

a Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, Gangnam-gu, Seoul 135-710, South Korea
b Department of Biomedical Engineering, Hanyang University, Seoul, South Korea
c Department of Biomedical Engineering, Catholic University of Daegu, Daegu, South Korea
d Department of Neurology, Seoul National University Boramae Hospital, Seoul, South Korea
e Department of Neurology, National Health Insurance Corporation Ilsan Hospital, Goyang, South Korea
f Department of Neurology, Washington University School of Medicine, St. Louis, MO, United States

Abstract
Recent studies suggest that the role of the cerebellum extends into cognitive regulation and that subcortical vascular dementia (SVaD) can result in cerebellar atrophy. However, there has been no evaluation of the cerebellar volume in the preclinical stage of SVaD. We aimed to compare cerebellar volume among patients with amnestic mild cognitive impairment (aMCI) and subcortical vascular mild cognitive impairment (svMCI) and evaluate which factors could have contributed to the cerebellar volume. Participants were composed of 355 patients with aMCI, svMCI, Alzheimer's disease (AD), and SVaD. Cerebellar volumes were measured using automated methods. A direct comparison of the cerebellar volume in SVaD and AD groups showed that the SVaD group had a statistically smaller cerebellar volume than the AD group. Additionally, the svMCI group had a smaller cerebellar volume than the aMCI group, with the number of lacunes (especially in the supratentorial regions) being associated with cerebellar volume. Cerebellar volumes were associated with some neuropsychological tests, digit span backward and ideomotor apraxia. These findings suggest that cerebellar atrophy may be useful in differentiating subtypes of dementia and the cerebellum plays a potential role in cognition. © 2012 Springer Science+Business Media, LLC.

Author Keywords
Cerebellar atrophy;  Lacunes;  Subcortical vascular MCI;  White matter hyperintensities

Document Type: Article
Source: Scopus

Sejvar, J.J.a , Kakooza, A.M.b , Foltz, J.L.c d , Makumbi, I.e , Atai-Omoruto, A.D.e , Malimbo, M.e , Ndyomugyenyi, R.e , Alexander, L.N.f , Abang, B.f , Downing, R.G.f , Ehrenberg, A.g , Guilliams, K.h i , Helmers, S.g , Melstrom, P.c j , Olara, D.f , Perlman, S.h , Ratto, J.k , Trevathan, E.l , Winkler, A.S.m , Dowell, S.F.n , Lwamafa, D.K.W.e
Clinical, neurological, and electrophysiological features of nodding syndrome in Kitgum, Uganda: An observational case series
(2013) The Lancet Neurology, 12 (2), pp. 166-174. 

a Division of High-Consequence Pathogens and Pathology, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention (CDC), Atlanta, GA, United States
b Department of Pediatrics and Child, Health Makerere University College of Health Sciences Kampala, Uganda
c Epidemic Intelligence Service, CDC, Atlanta, GA, United States
d Division of Nutrition, Physical Activity and Obesity, National Center for Chronic Disease Prevention and Health Promotion (NCCDHP), CDC, Atlanta, GA, United States
e Uganda Ministry of Health, Kampala, Uganda
f Global AIDS Program, Center for Global Health (CGH), CDC-Uganda, Entebbe, Uganda
g Department of Neurology, Emory University School of Medicine, Atlanta, GA, United States
h Division of Pediatric and Developmental Neurology, Department of Neurology, Washington University in St Louis, St Louis, MO, United States
i Division of Critical Care, Department of Pediatrics, Washington University in St Louis, St Louis, MO, United States
j Office of Smoking and Health, NCCDHP, CDC, Atlanta, GA, United States
k International Refugee Health Branch, CGH, CDC, Atlanta, GA, United States
l Departments of Epidemiology, Pediatrics, and Neurology, Saint Louis University, School of Public Health, MO, United States
m Department of Neurology, Technical University of Munich, Munich, Germany
n Division of Global Disease Detection and Emergency Response, CGH, CDC, Atlanta, GA, United States

Abstract
Background: Nodding syndrome is an unexplained illness characterised by head-bobbing spells. The clinical and epidemiological features are incompletely described, and the explanation for the nodding and the underlying cause of nodding syndrome are unknown. We aimed to describe the clinical and neurological diagnostic features of this illness. Methods: In December, 2009, we did a multifaceted investigation to assess epidemiological and clinical illness features in 13 parishes in Kitgum District, Uganda. We defined a case as a previously healthy child aged 5-15 years with reported nodding and at least one other neurological deficit. Children from a systematic sample of a case-control investigation were enrolled in a clinical case series which included history, physical assessment, and neurological examinations; a subset had electroencephalography (EEG), electromyography, brain MRI, CSF analysis, or a combination of these analyses. We reassessed the available children 8 months later. Findings: We enrolled 23 children (median age 12 years, range 7-15 years) in the case-series investigation, all of whom reported at least daily head nodding. 14 children had reported seizures. Seven (30%) children had gross cognitive impairment, and children with nodding did worse on cognitive tasks than did age-matched controls, with significantly lower scores on tests of short-term recall and attention, semantic fluency and fund of knowledge, and motor praxis. We obtained CSF samples from 16 children, all of which had normal glucose and protein concentrations. EEG of 12 children with nodding syndrome showed disorganised, slow background (n=10), and interictal generalised 2·5-3·0 Hz spike and slow waves (n=10). Two children had nodding episodes during EEG, which showed generalised electrodecrement and paraspinal electromyography dropout consistent with atonic seizures. MRI in four of five children showed generalised cerebral and cerebellar atrophy. Reassessment of 12 children found that six worsened in their clinical condition between the first evaluation and the follow-up evaluation interval, as indicated by more frequent head nodding or seizure episodes, and none had cessation or decrease in frequency of these episodes. Interpretation: Nodding syndrome is an epidemic epilepsy associated with encephalopathy, with head nodding caused by atonic seizures. The natural history, cause, and management of the disorder remain to be determined. Funding: Division of Global Disease Detection and Emergency Response, US Centers for Disease Control and Prevention. © 2013 Elsevier Ltd.

Document Type: Article
Source: Scopus

Suthar, M.S.a b , Diamond, M.S.c , Gale Jr., M.a d
West Nile virus infection and immunity
(2013) Nature Reviews Microbiology, 11 (2), pp. 115-128. 

a Department of Immunology, University of Washington, School of Medicine, 1959 NE Pacific Street, Seattle, WA 98195, United States
b Department of Pediatrics and Children's Healthcare of Atlanta, Emory Vaccine Center, Emory University, Atlanta, GA 30329, United States
c Departments of Medicine, Molecular Microbiology, and Pathology and Immunology, Washington University, St. Louis, MI 63110, United States
d Department of Microbiology, University of Washington, School of Medicine, Seattle, WA 98195-7735, United States

Abstract
West Nile virus (WNV) is an emerging neurotropic flavivirus that is transmitted to humans through the bite of an infected mosquito. WNV has disseminated broadly in the Western hemisphere and now poses a significant public health risk. The continuing spread of WNV, combined with the lack of specific therapeutics or vaccines to combat or prevent infection, imparts a pressing need to identify the viral and host processes that control the outcome of and immunity to WNV infection. Here, we provide an overview of recent research that has revealed the virus-host interface controlling WNV infection and immunity. © 2013 Macmillan Publishers Limited. All rights reserved.

Document Type: Review
Source: Scopus

Treyvaud, K.a b , Ure, A.a c , Doyle, L.W.a d e , Lee, K.J.a b , Rogers, C.E.f , Kidokoro, H.f , Inder, T.E.a f , Anderson, P.J.a b
Psychiatric outcomes at age seven for very preterm children: Rates and predictors
(2013) Journal of Child Psychology and Psychiatry and Allied Disciplines, . Article in Press. 

a Murdoch Childrens Research Institute, Vic., Australia
b Department of Paediatrics, University of Melbourne, Vic., Australia
c School of Psychological Sciences, University of Melbourne, Vic., Australia
d Department of Obstetrics and Gynaecology, University of Melbourne, Vic., Australia
e Clinical Research Development, Royal Women's Hospital, Vic., Australia
f Department of Pediatrics, Washington University, St Louis, USA

Abstract
Background: Uncertainty remains about the rate of specific psychiatric disorders and associated predictive factors for very preterm (VPT) children. The aims of this study were to document rates of psychiatric disorders in VPT children aged 7years compared with term born children, and to examine potential predictive factors for psychiatric diagnoses in VPT children. Methods: Participants were 177 VPT and 65 term born children. Perinatal medical data were collected, which included brain abnormalities detected using magnetic resonance imaging. The Infant-Toddler Social-Emotional Assessment (ITSEA) and Strengths and Difficulties Questionnaire (SDQ) were administered at 2 and 5years respectively. At 7years of age, the Developmental and Well-being Assessment (DAWBA) was used to indicate psychiatric diagnoses. Results: Compared with term born children, VPT children had three times the odds of meeting criteria for any psychiatric diagnosis at age 7years (odds ratio 3.03; 95% confidence interval 1.23, 7.47, p=.02). The most common diagnoses were anxiety disorders (11% VPT, 8% term), attention-deficit/hyperactivity disorder (10% VPT, 3% term) and autism spectrum disorder (4.5% VPT, 0% term). For VPT children, those with severe global brain abnormalities (p=.02), those who displayed social-emotional problems at age 5 (p=.000) and those with higher social risk at age 7 (p=.001) were more likely to meet criteria for a psychiatric illness at age 7. Conclusions: Compared with term born children, VPT children have higher rates of psychiatric diagnoses at early school age, predicted by neonatal brain abnormalities, prior social-emotional problems and social factors. © 2013 Association for Child and Adolescent Mental Health.

Author Keywords
Brain abnormality;  Mental health;  Predictor;  Preterm;  Psychiatric disorder

Document Type: Article in Press
Source: Scopus

Gardiner, S.K.a , Demirel, S.a , Gordon, M.O.b , Kass, M.A.b
Seasonal Changes in Visual Field Sensitivity and Intraocular Pressure in the Ocular Hypertension Treatment Study
(2013) Ophthalmology, . Article in Press. 

a Discoveries in Sight Laboratories, Devers Eye Institute, Legacy Research Institute, Legacy Health, Portland, Oregon
b Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, Missouri

Abstract
Purpose: Longitudinal testing plays a key role in glaucoma management. Variability between visits hampers the ability to monitor progression. It has previously been shown that average intraocular pressure (IOP) exhibits seasonal fluctuations. This study examines whether visual field sensitivity also exhibits seasonal fluctuations and seeks to determine whether such fluctuations are correlated to seasonal IOP effects. Design: Comparative case series. Participants: A total of 33 873 visits by 1636 participants enrolled in the Ocular Hypertension Treatment Study. Participants were split into 6 geographic zones according to the prevailing climate in their location. Testing: At each visit, standard automated perimetry was conducted on each eye, and IOP was measured. Main Outcome Measures: Mixed effects regression models were formed to look for sinusoidal periodic effects on the change in perimetric mean deviation since the last visit (ΔMD) and on IOP, both overall and within each zone. Results: When all the data were included, a significant seasonal effect on ΔMD was found with magnitude 0.06 dB, peaking in February (P < 0.001). Five of the 6 geographic zones exhibited significant seasonal effects on ΔMD, peaking between January and April, with magnitudes ranging from 0.04 dB (P = 0.049) to 0.21 dB (P < 0.001). Zones with greater climactic variation showed larger seasonal effects on ΔMD. All 6 zones exhibited a seasonal effect on IOP, peaking in January or February, with magnitudes ranging from 0.14 to 0.39 mmHg (P ≤ 0.02 in all cases). However, there was no evidence of a significant association between the magnitudes or dates of peaks of the 2 seasonal effects. Conclusions: The mean deviation was significantly higher in winter than in summer. There is no evidence of an association with seasonal IOP fluctuations. The cause of the seasonal effect on visual field sensitivity is unknown. These findings may help shed light on the glaucomatous disease process and aid efforts to reduce test-retest variability. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article. © 2013 American Academy of Ophthalmology.

Document Type: Article in Press
Source: Scopus

Feng, Y.a , Clayton, E.H.a , Chang, Y.b , Okamoto, R.J.a , Bayly, P.V.a c
Viscoelastic properties of the ferret brain measured in vivo at multiple frequencies by magnetic resonance elastography
(2013) Journal of Biomechanics, . Article in Press. 

a Department of Mechanical Engineering and Materials Science, Washington University in St. Louis, St. Louis, MO 63130, United States
b Department of Radiology, Washington University in St. Louis, St. Louis, MO 63130, United States
c Department of Biomedical Engineering, Washington University in St. Louis,, St. Louis, MO 63130, United States

Abstract
Characterization of the dynamic mechanical behavior of brain tissue is essential for understanding and simulating the mechanisms of traumatic brain injury (TBI). Changes in mechanical properties may also reflect changes in the brain due to aging or disease. In this study, we used magnetic resonance elastography (MRE) to measure the viscoelastic properties of ferret brain tissue in vivo. Three-dimensional (3D) displacement fields were acquired during wave propagation in the brain induced by harmonic excitation of the skull at 400 Hz, 600 Hz and 800 Hz. Shear waves with wavelengths in the order of millimeters were clearly visible in the displacement field, in strain fields, and in the curl of displacement field (which contains no contributions from longitudinal waves). Viscoelastic parameters (storage and loss moduli) governing dynamic shear deformation were estimated in gray and white matter for these excitation frequencies. To characterize the reproducibility of measurements, two ferrets were studied on three different dates each. Estimated viscoelastic properties of white matter in the ferret brain were generally similar to those of gray matter and consistent between animals and scan dates. In both tissue types G′ increased from approximately 3 kPa at 400 Hz to 7 kPa at 800 Hz and G″ increased from approximately 1 kPa at 400 Hz to 2 kPa at 800 Hz. These measurements of shear wave propagation in the ferret brain can be used to both parameterize and validate finite element models of brain biomechanics. © 2013 Elsevier Ltd. All rights reserved.

Author Keywords
Brain;  Magnetic resonance elastography;  MRE;  Shear modulus;  Viscoelasticity

Document Type: Article in Press
Source: Scopus

Lohoff, F.W.a , Hodge, R.a , Narasimhan, S.a , Nall, A.a , Ferraro, T.N.a , Mickey, B.J.b , Heitzeg, M.M.b , Langenecker, S.A.b , Zubieta, J.-K.b , Bogdan, R.c d , Nikolova, Y.S.e , Drabant, E.f , Hariri, A.R.e , Bevilacqua, L.g , Goldman, D.g , Doyle, G.A.a
Functional genetic variants in the vesicular monoamine transporter 1 modulate emotion processing
(2013) Molecular Psychiatry, . Article in Press. 

a Translational Research Laboratories, Department of Psychiatry, Center for Neurobiology and Behavior, University of Pennsylvania School of Medicine, Philadelphia, PA, USA
b Department of Psychiatry, Molecular and Behavioral Neuroscience Institute, University of Michigan, Ann Arbor, MI, USA
c 1] Department of Psychology and Neuroscience, Institute for Genome Sciences and Policy, Duke University, Durham, NC, USA
d Department of Psychology, Washington University in St Louis, St Louis, MO, USA
e Department of Psychology and Neuroscience, Institute for Genome Sciences and Policy, Duke University, Durham, NC, USA
f 23andMe, Mountain View, CA, USA
g Laboratory of Neurogenetics, National Institute on Alcohol Abuse and Alcoholism, Rockville, MD, USA

Abstract
Emotional behavior is in part heritable and often disrupted in psychopathology. Identification of specific genetic variants that drive this heritability may provide important new insight into molecular and neurobiological mechanisms involved in emotionality. Our results demonstrate that the presynaptic vesicular monoamine transporter 1 (VMAT1) Thr136Ile (rs1390938) polymorphism is functional in vitro, with the Ile allele leading to increased monoamine transport into presynaptic vesicles. Moreover, we show that the Thr136Ile variant predicts differential responses in emotional brain circuits consistent with its effects in vitro. Lastly, deep sequencing of bipolar disorder (BPD) patients and controls identified several rare novel VMAT1 variants. The variant Phe84Ser was only present in individuals with BPD and leads to marked increase monoamine transport in vitro. Taken together, our data show that VMAT1 polymorphisms influence monoamine signaling, the functional response of emotional brain circuits and risk for psychopathology.Molecular Psychiatry advance online publication, 22 January 2013; doi:10.1038/mp.2012.193.

Document Type: Article in Press
Source: Scopus

McLaughlin, B.A.a , Gidday, J.M.b
Poised for Success: Implementation of Sound Conditioning Strategies to Promote Endogenous Protective Responses to Stroke in Patients
(2013) Translational Stroke Research, 4 (1), pp. 104-113. 

a Department of Neurology and Pharmacology, JB Marshall Laboratory for Neurovascular Therapeutics, Vanderbilt University School of Medicine, Nashville, TN, 37221, United States
b Departments of Neurosurgery, Cell Biology and Physiology, and Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, MO, 63110, United States

Abstract
The following perspective represents our summary of questions, ideas, concerns, and recommendations expressed by speakers and discussants at the second Biennial Translational Preconditioning Workshop held in Miami in December 2011. © 2013 Springer Science+Business Media New York.

Author Keywords
Clinical trials;  Hypoxia;  Ischemia;  Meeting;  Neuroprotection;  Perconditioning;  Postconditioning;  Preconditioning;  Proceedings;  Stroke;  Translational stroke

Document Type: Article
Source: Scopus

Quinn, C.T.a , Robert C. McKinstryd , Dowling, M.M.f , Ball, W.S.b , Kraut, M.A.g , Casella, J.F.h , Dlamini, N.j , Ichord, R.N.l , Jordan, L.C.n , Kirkham, F.J.k , Noetzel, M.J.e , Steve Roach, E.c , Strouse, J.J.h , Kwiatkowski, J.L.m , Hirtz, D.i , DeBaun, M.R.o p
Acute silent cerebral ischemic events in children with sickle cell anemia
(2013) Archives of Neurology, 70 (1), pp. 58-65. 

a Department of Hematology, Cincinnati Children's Hospital Medical Center, Cincinnati, United States
b Department of Radiology, Cincinnati Children's Hospital Medical Center, Cincinnati, United States
c Department of Pediatrics and Neurology, Nationwide Children's Hospital, Columbus, OH, United States
d Department of Radiology and Pediatrics, Washington University School of Medicine, St. Louis, MO, United States
e Department of Neurology and Pediatrics, Washington University School of Medicine, St. Louis, MO, United States
f Department of Pediatrics and Neurology, University of Texas Southwestern Medical Center, Dallas, Johns Hopkins University School of Medicine, Baltimore, United States
g Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, United States
h Pediatrics, Division of Pediatric Hematology, Johns Hopkins University School of Medicine, Baltimore, United States
i Division of Extramural Research, National Institutes of Health/National Institute of Neurological Disorders and Stroke, Bethesda, MD, United States
j Department of Pediatric Neurology, Evelina Children's Hospital, Guy's and St Thomas' Hospital, London, United Kingdom
k University College London Institute of Child Health, London, United Kingdom
l Department of Neurology, Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA, United States
m Department of Hematology, Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA, United States
n Department of Neurology, Division of Pediatric Neurology, Vanderbilt University School of Medicine, Nashville, TN, United States
o Vanderbilt Children's Hospital, Nashville, TN, United States
p Vanderbilt Meharry Center for Sickle Cell Disease Excellence, 220 Children's Way, Rm 11206 DOT, Nashville, TN 37232-90000, United States

Abstract
Background: Irregular, sporadic episodes of ischemic brain injury are known to occur in sickle cell anemia (SCA), resulting in overt stroke and silent cerebral infarction. Ongoing ischemia in other organs is common in SCA but has never been documented in the brain. Objective: To test the hypothesis that acute silent cerebral ischemic events (ASCIEs) are frequent and potentially transient. Design: Cross-sectional and cohort study of children with SCA screened by magnetic resonance imaging (MRI) of the brain for a randomized clinical trial. Setting: Clinical trial setting in tertiary care centers. Patients: Asymptomatic children with SCA without known stroke, neurologic injury, or epilepsy not receiving treatment with transfusions or hydroxyurea. Main Outcome Measure: Incidence of ASCIEs calculated using single diffusion-weighted MRI scans (acute ischemic events that occurred within 10 days of the MRI). Results: Acute silent cerebral ischemic events were detected on 1.3% of MRIs (10 of 771) in 652 children (mean age, 10.0 years), with an incidence of 47.3 events per 100 patient-years (95% CI, 22.7-87.2). Two of 10 children with ASCIEs had follow-up MRIs of the brain; only 1 had silent cerebral infarction in the same location as the previously detected ASCIE. Conclusions: Children with SCA experience ongoing (chronic, intermittent) cerebral ischemia, sometimes reversible, far more frequently than previously recognized. The brain in SCA is at constant threat of ischemia. © 2013 American Medical Association.

Document Type: Article
Source: Scopus

Kipfmueller, F.a , Wyen, H.b , Borgman, M.A.c , Spinella, P.C.d , Wirth, S.e , Maegele, M.f g
Epidemiology, risk stratification and outcome of severe pediatric trauma [Epidemiologie, risikostratifizierung und behandlungsergebnisse nach schwerem kindlichen trauma]
(2013) Klinische Padiatrie, 225 (1), pp. 34-40. 

a Abteilung Neonatologie, Zentrum für Kinderheilkunde, Universität Bonn, Germany
b Klinik für Unfallchirurgie, Hand- und Rekonstruktive Chirurgie, Klinikum der Johann, Wolfgang Goethe-Universität, Frankfurt, Germany
c Brooke Army Medical Center, MCHE-DP/PICU, Ft. Sam Houston, United States
d Department of Pediatrics, St. Louis Childrens Hospital, Washington University School of Medicine, St. Louis, United States
e Helios Klinikum Wuppertal, Zentrum für Kinder- und Jugendmedizin, Universität Witten-Herdecke, Wuppertal, Germany
f Klinik für Unfallchirurgie, Orthopädie und Sporttraumatologie, Klinikum Köln-Merheim, Universität Witten-Herdecke, Ostmerheimerstr. 200, 51109 Köln, Germany
g IFOM, Institut für Forschung in der Operativen Medizin, Universitat Witten-Herdecke, Köln, Germany

Abstract
Accidents and trauma are the leading cause of hospital admissions and major contributors to mortality in children and adolescents. There are age-specific injury patterns and differences in the clinical presentation of pediatric trauma and treatment both at the scene and in the emergency department can be observed. In general, pediatric trauma-scores to appreciate injury severity are adapted from the adult population. The most important factor to increase mortality in the severely injured pediatric population is the extent of a concomitant traumatic brain injury (TBI). In addition, the acute trauma-associated coagulopathy, which is triggered multifactorial, is an independent prognostic marker for mortality in severe trauma. The complexity of all currently available trauma-scores for the pediatric population is one reason why these scores are not unequivocal recommended for the early use in pediatric trauma care. The pediatric BIG-Score was developed to allow an early prognostic stratification for pediatric trauma patients and includes with base excess (BE), INR (International Normalized Ratio) and GCS (Glasgow Coma Scale) relevant prognostic factors for poor outcome. Early risk stratification is crucial in pediatric trauma due to mortality rates ranging between 9% and 15% and with 50% of all fatalities to occur within the first 24 h of hospital admission. © Georg Thieme Verlag KG Stuttgart · New York.

Author Keywords
outcome;  pediatric trauma;  prognosis;  risk stratification

Document Type: Article
Source: Scopus

Scaltritti, M.a , Balota, D.A.b , Peressotti, F.a
Exploring the additive effects of stimulus quality and word frequency: The influence of local and list-wide prime relatedness
(2013) Quarterly Journal of Experimental Psychology, 66 (1), pp. 91-107. 

a Department of Developmental and Social Psychology, University of Padova, Via Venezia 8, 35131 Padua, Italy
b Department of Psychology, Washington University in St. Louis, St. Louis, MO, United States

Abstract
Stimulus quality and word frequency produce additive effects in lexical decision performance, whereas the semantic priming effect interacts with both stimulus quality and word frequency effects. This pattern places important constraints on models of visual word recognition. In Experiment 1, all three variables were investigated within a single speeded pronunciation study. The results indicated that the joint effects of stimulus quality and word frequency were dependent upon prime relatedness. In particular, an additive effect of stimulus quality and word frequency was found after related primes, and an interactive effect was found after unrelated primes. It was hypothesized that this pattern reflects an adaptive reliance on related prime information within the experimental context. In Experiment 2, related primes were eliminated from the list, and the interactive effects of stimulus quality and word frequency found following unrelated primes in Experiment 1 reverted to additive effects for the same unrelated prime conditions. The results are supportive of a flexible lexical processor that adapts to both local prime information and global list-wide context. © 2013 Copyright The Experimental Psychology Society.

Author Keywords
Semantic priming;  Stimulus quality;  Word frequency

Document Type: Article
Source: Scopus

Milchenko, M., Marcus, D.
Obscuring surface anatomy in volumetric imaging data
(2013) Neuroinformatics, 11 (1), pp. 65-75. 

Mallinckrodt Institute of Radiology, Washington University School of Medicine, Saint Louis, Campus B 8225, 4525 Scott Ave, St Louis, MO 63110, United States

Abstract
The identifying or sensitive anatomical features in MR and CT images used in research raise patient privacy concerns when such data are shared. In order to protect human subject privacy, we developed a method of anatomical surface modification and investigated the effects of such modification on image statistics and common neuroimaging processing tools. Common approaches to obscuring facial features typically remove large portions of the voxels. The approach described here focuses on blurring the anatomical surface instead, to avoid impinging on areas of interest and hard edges that can confuse processing tools. The algorithm proceeds by extracting a thin boundary layer containing surface anatomy from a region of interest. This layer is then "stretched" and "flattened" to fit into a thin "box" volume. After smoothing along a plane roughly parallel to anatomy surface, this volume is transformed back onto the boundary layer of the original data. The above method, named normalized anterior filtering, was coded in MATLAB and applied on a number of high resolution MR and CT scans. To test its effect on automated tools, we compared the output of selected common skull stripping and MR gain field correction methods used on unmodified and obscured data. With this paper, we hope to improve the understanding of the effect of surface deformation approaches on the quality of de-identified data and to provide a useful de-identification tool for MR and CT acquisitions. © 2012 Springer Science+Business Media, LLC.

Author Keywords
3D;  Biomedical imaging;  CT imaging;  Facial recognition;  MR imaging;  Privacy

Document Type: Article
Source: Scopus

Glass, J.E.a , Kristjansson, S.D.b , Bucholz, K.K.b
Perceived Alcohol Stigma: Factor Structure and Construct Validation
(2013) Alcoholism: Clinical and Experimental Research, 37 (SUPPL.1), pp. E237-E246. 

a George Warren Brown School of Social, Work Washington University, St. Louis, MO, United States
b Department of Psychiatry, Midwest Alcoholism Research Center, Washington University School of Medicine, St. Louis, MO, United States

Abstract
Introduction: There has been an increasing interest in studying the stigma of alcohol use disorders (AUDs) yet scant research has evaluated the conceptualization and measurement of alcohol stigma. This study examined the measurement properties (i.e., factor structure) and validity of the alcohol-adapted Perceived Devaluation-Discrimination scale (PDD), which assesses the construct of perceived alcohol stigma (PAS). Methods: Our sample included 34,386 respondents from the Wave 2 assessment in the National Epidemiologic Survey on Alcohol and Related Conditions, a population-representative survey of noninstitutionalized U.S. adults. Analytic procedures included confirmatory factor analysis and structural equation modeling. Results: One-factor (perceived devaluation-discrimination) and 2-factor (perceived devaluation, perceived discrimination) confirmatory factor analytic models fit the data well (Comparative Fit Index = 0.958, Tucker-Lewis Index = 0.942, Root Mean Square Error of Approximation = 0.056; Comparative Fit Index = 0.962, Tucker-Lewis Index = 0.946, Root Mean Square Error of Approximation = 0.054; respectively) when adjusting for item wording effects with a latent method factor. Despite having a better fit to the data, χ2 (1) = 542, p &lt; 0.0001, the 2 factors were highly correlated (r = 0.90), which led us to favor a 1-factor model. Structural equation models found that the inverse relationship between PAS and perceived interpersonal social support was strongest for persons with a stigmatized labeling status. The same was not true in analyses predicting social network involvement. Conclusions: A 1-factor solution of PAS had superior parsimony. The alcohol-adapted PDD appears to be a psychometrically sound measure and exhibits relationships that are consistent with modified labeling theory. © 2012 by the Research Society on Alcoholism.

Author Keywords
Alcohol use disorders;  Confirmatory factor analysis;  Perceived stigma;  Social consequences;  Structural equation modeling

Document Type: Article
Source: Scopus

Sartor, C.E.a , McCutcheon, V.V.b , Callahan O'Leary, C.b , Van Buren, D.J.b , Allsworth, J.E.c , Jeffe, D.B.d , Cottler, L.B.e
Lifetime trauma exposure and posttraumatic stress disorder in women sentenced to drug court
(2012) Psychiatry Research, 200 (2-3), pp. 602-608. 

a Department of Psychiatry, Yale School of Medicine, New Haven CT, United States
b Department of Psychiatry, Washington University School of Medicine, St. Louis MO, United States
c Department of Obstetrics and Gynecology, Washington University School of Medicine, St. Louis MO, United States
d Department of Internal Medicine, Washington University School of Medicine, St. Louis MO, United States
e Department of Epidemiology, University of Florida College of Medicine, Gainesville FL, United States

Abstract
The aims of this study were to characterize trauma exposure and posttraumatic stress disorder (PTSD) in female drug court participants and test for differences in socioeconomic status and familial status between women with: (i) no trauma exposure, (ii) trauma exposure without PTSD, and (iii) trauma exposure resulting in PTSD. Three hundred and nineteen women were recruited from drug courts. Rates of exposure and likelihood of traumatic events leading to PTSD were examined, sociodemographic characteristics were compared across groups, and a logistic regression analysis was conducted to test for differences in PTSD risk for assaultive vs. non-assaultive events. Twenty percent of participants met PTSD criteria, 71% had trauma exposure without PTSD, and 9% did not endorse any traumatic events. Prostitution and homelessness were more prevalent in women with vs. without a history of trauma, but among trauma-exposed women prevalences did not vary by PTSD status. No differences in risk for PTSD were found between assaultive and non-assaultive events (OR=0.91; 95%CI: 0.48-1.75). Women sentenced to drug court represent a heavily trauma-exposed population, for whom risk for PTSD is not limited to assaultive events. Within this high-risk population, trauma is associated with elevated rates of homelessness and prostitution, even in the absence of PTSD. © 2012 Elsevier Ireland Ltd.

Author Keywords
Drug court;  Sexual assault;  Traumatic event;  Women

Document Type: Article
Source: Scopus

Stoker, G.E.a , Lenke, L.G.a , Dorward, I.G.b
Posterior vertebral column resection for the treatment of dystrophic kyphosis associated with type-1 neurofibromatosis: A case report and review of the literature
(2012) Spine, 37 (26), pp. E1659-E1664. 

a Department of Orthopaedic Surgery, Washington University School of Medicine, Campus Box 8233, 660 S Euclid Ave, St. Louis, MO 63110, United States
b Department of Neurosurgery, Washington University School of Medicine, St. Louis, MO, United States

Abstract
STUDY DESIGN. Case report. OBJECTIVE. To describe the use of posterior-only vertebral column resection and postoperative traction for spinal deformity associated with type-1 neurofibromatosis (NF1). SUMMARY OF BACKGROUND DATA. Vertebral deformity, namely, thoracic scoliosis, is the predominant orthopedic manifestation of NF1. Patients may present with debilitating pain and rarely, myelopathy. The commonly dystrophic nature of these deformities makes them particularly recalcitrant to surgical correction. Traditionally, circumferential arthrodesis via combined anterior and posterior approaches has been recommended. METHODS. Clinical and radiographical case review. RESULTS. A 14-year-old adolescent boy with NF1, severe cervicothoracic angular kyphosis, thoracic dislocation, and myelopathy presented status postmultiple anterior and posterior spinal fusions. The patient underwent posterior-only vertebral column resection after 6 weeks of halo-gravity traction. The surgery consisted of thoracic laminectomies, total corpectomies of T3 and T4, circumferential fusion, and posterior instrumentation from the occiput to T11. Autologous rib and iliac crest grafts were used as fusion substrate. Postoperatively, a halo vest was worn for 4 months to support the correction of his chin-on-chest deformity. The patient's neurological status returned to normal by 6 weeks postoperatively, and solid fusion was radiologically evident after 1 year. CONCLUSION. We think that posterior-only vertebral column resection represents a safe and efficacious but technically challenging option for the treatment of angular kyphotic spinal deformity and associated neurological deficit in patients with NF1. © 2012, Lippincott Williams & Wilkins.

Author Keywords
Dislocation;  Kyphosis;  Neurofibromatosis;  Spinal deformity;  Vertebral column resection;  Vertebrectomy

Document Type: Review
Source: Scopus

O'Neil, B.a , Prichep, L.S.b , Naunheim, R.c , Chabot, R.b
Quantitative brain electrical activity in the initial screening of mild traumatic brain injuries
(2012) Western Journal of Emergency Medicine, 13 (5), pp. 394-400. 

a Wayne State University, Department of Emergency Medicine, Detroit, MI, United States
b New York University School of Medicine, Brain Research Laboratories, Department of Psychiatry, New York, NY, United States
c Washington University School of Medicine, Division of Emergency Medicine, St. Louis, MO, United States

Abstract
Introduction: The incidence of emergency department (ED) visits for Traumatic Brain Injury (TBI) in the United States exceeds 1,000,000 cases/year with the vast majority classified as mild (mTBI). Using existing computed tomography (CT) decision rules for selecting patients to be referred for CT, such as the New Orleans Criteria (NOC), approximately 70% of those scanned are found to have a negative CT. This study investigates the use of quantified brain electrical activity to assess its possible role in the initial screening of ED mTBI patients as compared to NOC. Methods: We studied 119 patients who reported to the ED with mTBI and received a CT. Using a hand-held electroencephalogram (EEG) acquisition device, we collected data from frontal leads to determine the likelihood of a positive CT. The brain electrical activity was processed off-line to generate an index (TBI-Index, biomarker). This index was previously derived using an independent population, and the value found to be sensitive for significant brain dysfunction in TBI patients. We compared this performance of the TBI-Index to the NOC for accuracy in prediction of positive CT findings. Results: Both the brain electrical activity TBI-Index and the NOC had sensitivities, at 94.7% and 92.1% respectively. The specificity of the TBI-Index was more than twice that of NOC, 49.4% and 23.5% respectively. The positive predictive value, negative predictive value and the positive likelihood ratio were better with the TBI-Index. When either the TBI-Index or the NOC are positive (combining both indices) the sensitivity to detect a positive CT increases to 97%. Conclusion: The hand-held EEG device with a limited frontal montage is applicable to the ED environment and its performance was superior to that obtained using the New Orleans criteria. This study suggests a possible role for an index of brain function based on EEG to aid in the acute assessment of mTBI patients.

Document Type: Article
Source: Scopus

 

January 24, 2013

Levinson, C.A., Rodebaugh, T.L., Bertelson, A.D.
Prolonged Exposure Therapy Following Awareness Under Anesthesia: A Case Study
(2013) Cognitive and Behavioral Practice, 20 (1), pp. 74-80. 

Washington University in St. Louis, United States

Abstract
Awareness during surgery is estimated to effect between 40,000 to 140,000 patients per year in the United States, and there is a growing literature suggesting that this event can lead to the development of posttraumatic stress disorder (PTSD). The current article describes treatment implemented from a manualized protocol of a woman diagnosed with PTSD following awareness during a routine surgery. Prolonged exposure therapy was delivered to the client over 12 sessions. Treatment consisted of psychoeducation, imaginal exposure, in-vivo exposure, breathing retraining, progressive muscle relaxation, and homework assignments. At treatment completion and at follow-up 10. weeks after completion of therapy, the client no longer met criteria for PTSD. Prolonged exposure therapy for PTSD is an effective treatment that alleviates symptoms of PTSD from awareness during surgery. © 2012.

Author Keywords
Awareness under anesthesia;  Post-traumatic stress disorder;  Prolonged exposure therapy

Document Type: Article
Source: Scopus

Power, J.D.a , Petersen, S.E.a b c d e f
Control-related systems in the human brain
(2013) Current Opinion in Neurobiology, . Article in Press. 

a Department of Neurology, Washington University School of Medicine, USA
b Department of Radiology, Washington University School of Medicine, USA
c Department of Anatomy and Neurobiology, Washington University School of Medicine, USA
d Department of Psychology, Washington University in Saint Louis, USA
e Department of Neurosurgery, Washington University School of Medicine, USA
f Department of Biomedical Engineering, Washington University in Saint Louis, USA

Abstract
A fundamental question in cognitive neuroscience is how the human brain self-organizes to perform tasks. Multiple accounts of this self-organization are currently influential and in this article we survey one of these accounts. We begin by introducing a psychological model of task control and several neuroimaging signals it predicts. We then discuss where such signals are found across tasks with emphasis on brain regions where multiple control signals are present. We then present results derived from spontaneous task-free functional connectivity between control-related regions that dovetail with distinctions made by control signals present in these regions, leading to a proposal that there are at least two task control systems in the brain. This prompts consideration of whether and how such control systems distinguish themselves from other brain regions in a whole-brain context. We present evidence from whole-brain networks that such distinctions do occur and that control systems comprise some of the basic system-level organizational elements of the human brain. We close with observations from the whole-brain networks that may suggest parsimony between multiple accounts of cognitive control. © 2013 Elsevier Ltd. All rights reserved.

Document Type: Article in Press
Source: Scopus

Vannucci, A., Kras, J.F.
Decision Making, situation awareness, and communication skills in the operating room
(2013) International Anesthesiology Clinics, 51 (1), pp. 105-127. 

Department of Anesthesiology, Washington University, St Louis-School of Medicine, 660 South Euclid Avenue, St Louis, MO 63110, United States

Document Type: Article
Source: Scopus

Tan, J.A.a , Helsten, D.b
Intraoperative handoffs
(2013) International Anesthesiology Clinics, 51 (1), pp. 31-42. 

a Anderson Cancer Center, University of Texas, Anesthesiology and PeriOperative Medicine, 1400 Holcombe Blvd., Houston, TX 77030, United States
b Washington University School of Medicine, Washington University, St Louis, MO, United States

Document Type: Article
Source: Scopus

Hadlandsmyth, K.a , White, K.S.a , Krone, R.J.b
Quality of Life in Patients with Non-CAD Chest Pain: Associations to Fear of Pain and Psychiatric Disorder Severity
(2013) Journal of Clinical Psychology in Medical Settings, pp. 1-10. Article in Press. 

a Department of Psychology, University of Missouri-Saint Louis, St. Louis, United States
b Cardiovascular Division, Washington University School of Medicine, St. Louis, United States

Abstract
Chest pain in the absence of identified cardiac cause, or non-cardiac chest pain (NCCP), is a common condition that may result in impaired quality of life. Theories of NCCP put forward that patients who react to cardiopulmonary sensations with fear may avoid activities that elicit cardiac sensations. Co-morbid psychiatric disorders, which are prevalent in this population, may predispose individuals to be more vigilant to physiological sensations, including cardiac-related symptoms. The daily impact of avoiding cardiopulmonary cues may limit quality of life. This study examined psychiatric disorders, fear of pain, and quality of life in 30 non-coronary artery disease (CAD) chest pain patients. Psychiatric disorder severity was independently associated with mental health related quality of life and fear of pain was independently associated with physical health related quality of life. This research adds understanding to contributory factors to impaired quality of life among patients with non-CAD chest pain. © 2013 Springer Science+Business Media New York.

Author Keywords
Fear of pain;  Non-cardiac chest pain;  Quality of life

Document Type: Article in Press
Source: Scopus

Ju, Y.-E.S.
RBD in adults younger than fifty years old
(2013) Sleep Medicine, . Article in Press. 

Department of Neurology, Washington University in Saint Louis, Saint Louis, MO, United States

Abstract
Rapid eye movement (REM) sleep behavior disorder (RBD) occurring prior to age 50 is termed "early-onset" RBD. Early-onset RBD comprises a substantial minority of cases, and demonstrates the differences in demographics, comorbidities, and clinical considerations from previously described typical RBD with onset >50 years. The world literature on RBD is reviewed with specific focus on features that distinguish early-onset RBD, including more gender parity, increased proportion of idiopathic cases, increased proportion of cases associated with narcolepsy, parasomnia overlap disorder, antidepressants, and possibly autoimmune disorders, and clinical presentation. © 2012 Elsevier B.V. All rights reserved.

Author Keywords
Antidepressant;  Autoimmune;  Narcolepsy;  Parasomnia;  Parasomnia overlap disorder (POD);  REM sleep behavior disorder (RBD)

Document Type: Article in Press
Source: Scopus

Johnson, E.O.a , Hancock, D.B.a , Levy, J.L.b , Gaddis, N.C.b , Saccone, N.L.c , Bierut, L.J.d , Page, G.P.e
Imputation across genotyping arrays for genome-wide association studies: assessment of bias and a correction strategy
(2013) Human Genetics, pp. 1-14. Article in Press. 

a Behavioral Health Epidemiology Program, RTI International, 3040 Cornwallis Road, Research Triangle Park, 27709-12194, United States
b Research Computing Division, RTI International, Research Triangle Park, 27709, United States
c Department of Genetics, Washington University, St. Louis, 63110, United States
d Department of Psychiatry, Washington University, St. Louis, 63110, United States
e Genomics, Statistical Genetics, and Environmental Research Program, RTI International, Atlanta, 30341, United States

Abstract
A great promise of publicly sharing genome-wide association data is the potential to create composite sets of controls. However, studies often use different genotyping arrays, and imputation to a common set of SNPs has shown substantial bias: a problem which has no broadly applicable solution. Based on the idea that using differing genotyped SNP sets as inputs creates differential imputation errors and thus bias in the composite set of controls, we examined the degree to which each of the following occurs: (1) imputation based on the union of genotyped SNPs (i.e., SNPs available on one or more arrays) results in bias, as evidenced by spurious associations (type 1 error) between imputed genotypes and arbitrarily assigned case/control status; (2) imputation based on the intersection of genotyped SNPs (i.e., SNPs available on all arrays) does not evidence such bias; and (3) imputation quality varies by the size of the intersection of genotyped SNP sets. Imputations were conducted in European Americans and African Americans with reference to HapMap phase II and III data. Imputation based on the union of genotyped SNPs across the Illumina 1M and 550v3 arrays showed spurious associations for 0.2 % of SNPs: ~2,000 false positives per million SNPs imputed. Biases remained problematic for very similar arrays (550v1 vs. 550v3) and were substantial for dissimilar arrays (Illumina 1M vs. Affymetrix 6.0). In all instances, imputing based on the intersection of genotyped SNPs (as few as 30 % of the total SNPs genotyped) eliminated such bias while still achieving good imputation quality. © 2013 Springer-Verlag Berlin Heidelberg.

Document Type: Article in Press
Source: Scopus

Williams, A.J.a , Peterson, D.S.a , Earhart, G.M.a b c
Gait coordination in Parkinson disease: Effects of step length and cadence manipulations
(2013) Gait and Posture, . Article in Press. 

a Program in Physical Therapy, Washington University in St. Louis School of Medicine, St. Louis, MO 63108, United States
b Department of Anatomy and Neurobiology, Washington University in St. Louis School of Medicine, St. Louis, MO 63105, United States
c Department of Neurology, Washington University in St. Louis School of Medicine, St. Louis, MO 63105, United States

Abstract
Background: Gait impairments are well documented in those with PD. Prior studies suggest that gait impairments may be worse and ongoing in those with PD who demonstrate FOG compared to those with PD who do not. Purpose: Our aim was to determine the effects of manipulating step length and cadence individually, and together, on gait coordination in those with PD who experience FOG, those with PD who do not experience FOG, healthy older adults, and healthy young adults. Methods: Eleven participants with PD and FOG, 16 with PD and no FOG, 18 healthy older, and 19 healthy young adults walked across a GAITRite walkway under four conditions: Natural, Fast (+50% of preferred cadence), Small (-50% of preferred step length), and SmallFast (+50% cadence and -50% step length). Coordination (i.e. phase coordination index) was measured for each participant during each condition and analyzed using mixed model repeated measure ANOVAs. Results: FOG was not elicited. Decreasing step length alone or decreasing step length and increasing cadence together affected coordination. Small steps combined with fast cadence resulted in poorer coordination in both groups with PD compared to healthy young adults and in those with PD and FOG compared to healthy older adults. Conclusions: Coordination deficits can be identified in those with PD by having them walk with small steps combined with fast cadence. Short steps produced at high rate elicit worse coordination than short steps or fast steps alone. © 2012 Elsevier B.V. All rights reserved.

Author Keywords
Coordination;  Freezing of gait;  Parkinson disease

Document Type: Article in Press
Source: Scopus

Jagadeesan, N., Wolfson, M., Chen, Y., Willingham, M., Avidan, M.S.
Brain monitoring during general anesthesia
(2013) Trends in Anaesthesia and Critical Care, . Article in Press. 

Washington University School of Medicine, USA

Abstract
Electroencephalography (EEG) offers utility as a surrogate monitor of anesthetic depth, potentially facilitating a "Goldilocks" anesthetic plan of "just right" patient centered dosing. Despite the proposed benefits, clinical incorporation has been slow, and there have been many conflicting results regarding the ability of EEG monitoring to improve clinical outcomes. This review summarizes features of EEG waveforms during wakefulness, sedation and general anesthesia. The literature regarding the effectiveness of processed EEG monitoring in preventing intraoperative awareness with recall is critically summarized; the strongest evidence for processed EEG monitoring is in the setting of total intravenous anesthesia. Preliminary evidence regarding the utility of processed EEG monitoring in preventing unnecessarily deep anesthesia and its hypothesized adverse effects is discussed. A provocative association has been noted between certain EEG features, such as burst suppression, and adverse early and intermediate term outcomes, such as delirium and death. However, whether such associations are causal or epiphenomenal is currently unknown. Finally, the limitations of current EEG monitors and the features of an ideal EEG monitor are described. © 2012 Elsevier Ltd. All rights reserved.

Author Keywords
Bispectral index;  Brain monitoring;  Depth of anesthesia;  Electroencephalogram;  Memory

Document Type: Article in Press
Source: Scopus

Diggs-Andrews, K.A., Gutmann, D.H.
Modeling cognitive dysfunction in neurofibromatosis-1
(2013) Trends in Neurosciences, . Article in Press. 

Department of Neurology, Washington University School of Medicine, Box 8111, 660 South Euclid Avenue, St. Louis, MO 63110, USA

Abstract
Cognitive dysfunction, including significant impairments in learning, behavior, and attention, is found in over 10% of children in the general population. However, in the common inherited cancer predisposition syndrome, neurofibromatosis type 1 (NF1), the prevalence of these cognitive deficits approaches 70%. As a monogenic disorder, NF1 provides a unique genetic tool to identify and dissect mechanistically the molecular and cellular bases underlying cognitive dysfunction. In this review, we discuss Nf1 fly and mouse systems that mimic many of the cognitive abnormalities seen in children with NF1. Further, we describe discoveries from these models that have uncovered defects in the regulation of Ras activity, cAMP generation, and dopamine homeostasis as key mechanisms important for cognitive dysfunction in children with NF1. © 2012 Elsevier Ltd. All rights reserved.

Author Keywords
attention deficits;  cyclic AMP;  dopamine;  learning;  neurofibromin;  NF1

Document Type: Article in Press
Source: Scopus

Harbour, J.W.a b , Roberson, E.D.O.c , Anbunathan, H.c , Onken, M.D.d , Worley, L.A.d , Bowcock, A.M.e
Recurrent mutations at codon 625 of the splicing factor SF3B1 in uveal melanoma
(2013) Nature Genetics, . Article in Press. 

a 1] Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, Missouri, USA
b Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida, USA, and Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, Florida, USA
c Department of Genetics, Washington University School of Medicine, St. Louis, Missouri, USA
d Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, Missouri, USA
e 1] Department of Genetics, Washington University School of Medicine, St. Louis, Missouri, USA

Abstract
Uveal melanoma is the most common primary cancer of the eye and often results in fatal metastasis. Here, we describe mutations occurring exclusively at codon 625 of the SF3B1 gene, encoding splicing factor 3B subunit 1, in low-grade uveal melanomas with good prognosis. Thus, uveal melanoma is among a small group of cancers associated with SF3B1 mutations, and these mutations denote a distinct molecular subset of uveal melanomas.

Document Type: Article in Press
Source: Scopus

Knobloch, M.a b , Braun, S.M.G.a b , Zurkirchen, L.b , Von Schoultz, C.b , Zamboni, N.c , Araúzo-Bravo, M.J.d , Kovacs, W.J.b , Karalay, O.b , Suter, U.b , MacHado, R.A.C.a b , Roccio, M.e , Lutolf, M.P.e , Semenkovich, C.F.f , Jessberger, S.a b
Metabolic control of adult neural stem cell activity by Fasn-dependent lipogenesis
(2013) Nature, 493 (7431), pp. 226-230. 

a Brain Research Institute, Faculty of Medicine, University of Zurich, 8057 Zurich, Switzerland
b Institute of Molecular Health Sciences, Department of Biology, Swiss Federal Institute of Technology (ETH) Zurich, 8093 Zurich, Switzerland
c Institute of Molecular Systems Biology, Department of Biology, ETH Zurich, 8093 Zurich, Switzerland
d Department of Cell and Developmental Biology, Max Planck Institute for Molecular Biomedicine, 48149 Muenster, Germany
e Institute of Bioengineering, Ecole Polytechnique Federale de Lausanne, 1015 Lausanne, Switzerland
f Washington University School of Medicine, Division of Endocrinology Metabolism and Lipid Research, St. Louis, MO 63110, United States

Abstract
Mechanisms controlling the proliferative activity of neural stem and progenitor cells (NSPCs) have a pivotal role to ensure life-long neurogenesis in the mammalian brain. How metabolic programs are coupled with NSPC activity remains unknown. Here we show that fatty acid synthase (Fasn), the key enzyme of de novo lipogenesis, is highly active in adult NSPCs and that conditional deletion of Fasn in mouse NSPCs impairs adult neurogenesis. The rate of de novo lipid synthesis and subsequent proliferation of NSPCs is regulated by Spot14, a gene previously implicated in lipid metabolism, that we found to be selectively expressed in low proliferating adult NSPCs. Spot14 reduces the availability of malonyl-CoA, which is an essential substrate for Fasn to fuel lipogenesis. Thus, we identify here a functional coupling between the regulation of lipid metabolism and adult NSPC proliferation. © 2013 Macmillan Publishers Limited. All rights reserved.

Document Type: Article
Source: Scopus

Leuthardt, E.C.
Developing a new model for the invention and translation of neurotechnologies in academic neurosurgery
(2013) Neurosurgery, 72 (SUPPL. 1), pp. A182-A192. 

Department of Neurological Surgery, School of Medicine, Washington University, St. Louis, MO, United States

Abstract
Background: There is currently an acceleration of new scientific and technical capabilities that create new opportunities for academic neurosurgery. To engage these changing dynamics, the Center for Innovation in Neuroscience and Technology (CINT) was created on the premise that successful innovation of device-related ideas relies on collaboration between multiple disciplines. The CINT has created a unique model that integrates scientific, medical, engineering, and legal/business experts to participate in the continuum from idea generation to translation. Objective: To detail the method by which this model has been implemented in the Department of Neurological Surgery at Washington University in St. Louis and the experience that has been accrued thus far. Methods: The workflow is structured to enable cross-disciplinary interaction, both intramurally and extramurally between academia and industry. This involves a structured method for generating, evaluating, and prototyping promising device concepts. The process begins with the "invention session," which consists of a structured exchange between inventors from diverse technical and medical backgrounds. Successful ideas, which pass a separate triage mechanism, are then sent to industry-sponsored multidisciplinary fellowships to create functioning prototypes. Results: After 3 years, the CINT has engaged 32 clinical and nonclinical inventors, resulting in 47 ideas, 16 fellowships, and 12 patents, for which 7 have been licensed to industry. Financial models project that if commercially successful, device sales could have a notable impact on departmental revenue. Conclusion: The CINT is a model that supports an integrated approach from the time an idea is created through its translational development. To date, the approach has been successful in creating numerous concepts that have led to industry licenses. In the long term, this model will create a novel revenue stream to support the academic neurosurgical mission. Copyright © 2012 by the Congress of Neurological Surgeons.

Author Keywords
Devices;  Innovation;  Inventions;  Licensing;  Neurotechnology;  Patents;  Translational medicine

Document Type: Article
Source: Scopus

Rosman, I.S.a , Liang, L.-C.b , Patil, S.c , Bayliss, S.J.a , White, A.J.d
Febrile ulceronecrotic mucha-habermann disease with central nervous system vasculitis
(2013) Pediatric Dermatology, 30 (1), pp. 90-93. 

a Departments of Internal Medicine and Pediatrics, School of Medicine Washington University, St. Louis Children's Hospital, St. Louis, MO, United States
b Department of Pediatrics, Cedars-Sinai Medical Center, Los Angeles, CA, United States
c Department of Pathology, School of Medicine Washington University, St. Louis Children's Hospital, St. Louis, MO, United States
d Division of Rheumatology, School of Medicine Washington University, St. Louis Children's Hospital, 660 S. Euclid Avenue, St. Louis, MO 63110, United States

Abstract
Febrile ulceronecrotic Mucha-Habermann disease (FUMHD) is a severe variant of pityriasis lichenoides et varioliformis acuta (PLEVA). We report a case of FUMHD in an 11-year-old boy who subsequently developed neurologic symptoms and was found to have necrotizing vasculitis on brain biopsy. Over 5 years of follow-up, he had one biopsy-proven recurrence of his skin lesions and continued rehabilitation and treatment for residual neurologic complications. This case provides histological evidence of central nervous system vasculitis associated with FUMHD. Our patient's disease was eventually controlled with cyclophosphamide. © 2012 Wiley Periodicals, Inc.

Document Type: Article
Source: Scopus

Murphy, R.K.J.a , Reynolds, M.R.a , Mansur, D.B.b , Smyth, M.D.a c
Gamma Knife surgery for a hemangioma of the cavernous sinus in a child: Case report
(2013) Journal of Neurosurgery: Pediatrics, 11 (1), pp. 74-78. 

a Department of Neurological Surgery, St. Louis Children's Hospital, Washington University School of Medicine, St. Louis, MI, United States
b Department of Radiation Oncology, Case Western Reserve University School of Medicine, Cleveland, OH, United States
c Division of Pediatric Neurosurgery, St. Louis Children's Hospital, Washington University School of Medicine, St. Louis, MO, United States

Abstract
Cavernous sinus (CS) hemangiomas are rare vascular abnormalities that constitute 0.4%-2% of all lesions within the CS. Cavernous sinus hemangiomas are high-flow vascular tumors that tend to hemorrhage profusely during resection, leading to incomplete resection and high morbidity and mortality. While Gamma Knife surgery (GKS) has proven to be an effective treatment of CS hemangiomas in the adult population, few reports of GKS for treatment of CS hemangiomas exist in the pediatric literature. Here, the authors present the first case of a 15-year-old girl with a biopsy-proven CS hemangioma who achieved complete resolution of her symptoms and a complete imaging-defined response following GKS. If suspicion for a CS hemangioma is high in a pediatric patient, GKS may be considered as an effective treatment modality, thus avoiding the morbidities of open resection. ©ANNS, 2013.

Author Keywords
Cavernous sinus;  Gamma Knife;  Hemangioma;  Oncology;  Pediatric neurosurgery;  Radiosurgery

Document Type: Article
Source: Scopus

 

Elfenbein, H.A.
Nonverbal dialects and accents in facial expressions of emotion
(2013) Emotion Review, 5 (1), pp. 90-96. Cited 3 times.

Washington University in St. Louis, Olin School of Business, 1 Brookings Drive, Saint Louis, MO 63130, United States

Abstract
This article focuses on a theoretical account integrating classic and recent findings on the communication of emotions across cultures: a dialect theory of emotion. Dialect theory uses a linguistic metaphor to argue emotion is a universal language with subtly different dialects. As in verbal language, it is more challenging to understand someone speaking a different dialect - which fits with empirical support for an in-group advantage, whereby individuals are more accurate judging emotional expressions from their own cultural group versus foreign groups. Dialect theory has sparked controversy with its implications for dominant theories about cross-cultural differences in emotion. This article reviews the theory, its mounting body of evidence, evidence for alternative accounts, and practical implications for multicultural societies. © The Author(s) 2013.

Author Keywords
emotion;  expression;  facial expression;  nonverbal accents;  nonverbal dialects;  perception;  recognition

Document Type: Review
Source: Scopus

Grubb Jr., R.L.a b , Powers, W.J.d , Clarke, W.R.e , Adams Jr., H.P.f , Derdeyn, C.P.a b c
Response
(2013) Journal of Neurosurgery, 118 (1), pp. 22-24. 

a Department of Neurological Surgery, Washington University School of Medicine, St. Louis, MO, United States
b Department of Radiology, Washington University School of Medicine, St. Louis, MO, United States
c Department of Neurology, Washington University School of Medicine, St. Louis, MO, United States
d Department of Neurology, University of North Carolina School of Medicine, Chapel Hill, NC, United States
e Clinical Trials Statistics and Data Management Center, University of Iowa College of Public Health, Iowa City, IA, United States
f Department of Neurology, University of Iowa Carver School of Medicine, Iowa City, IA, United States

Document Type: Note
Source: Scopus

Washington, C.W., Grubb Jr., R.L.
Response
(2013) Journal of Neurosurgery, 118 (1), p. 213. 

Washington University in St. Louis, St. Louis, MO, United States

Document Type: Letter
Source: Scopus

Harms, M.P.a , Wang, L.b , Csernansky, J.G.b , Barch, D.M.a c
Structure-function relationship of working memory activity with hippocampal and prefrontal cortex volumes
(2013) Brain Structure and Function, 218 (1), pp. 173-186. Cited 1 time.

a Department of Psychiatry, Washington University School of Medicine, 660 S. Euclid Ave., Box 8134, St. Louis, MO 63110, United States
b Department of Psychiatry and Behavioral Sciences, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States
c Department of Psychology, Washington University, St. Louis, MO, United States

Abstract
A rapidly increasing number of studies are quantifying the system-level network architecture of the human brain based on structural-to-structural and functional-to-functional relationships. However, a largely unexplored area is the nature and existence of "cross-modal" structural-functional relationships, in which, for example, the volume (or other morphological property) of one brain region is related to the functional response to a given task either in that same brain region, or another brain region. The present study investigated whether the gray matter volume of a selected group of structures (superior, middle, and inferior frontal gyri, thalamus, and hippocampus) was correlated with the fMRI response to a working memory task, within a mask of regions previously identified as involved with working memory. The subjects included individuals with schizophrenia, their siblings, and healthy controls (n = 154 total). Using rigorous permutation testing to define the null distribution, we found that the volume of the superior and middle frontal gyri was correlated with working memory activity within clusters in the intraparietal sulcus (i.e., dorsal parietal cortex) and that the volume of the hippocampus was correlated with working memory activity within clusters in the dorsal anterior cingulate cortex and left inferior frontal gyrus. However, we did not find evidence that the identified structure-function relationships differed between subject groups. These results show that long-distance structural-functional relationships exist within the human brain. The study of such cross-modal relationships represents an additional approach for studying systems-level interregional brain networks. © 2012 Springer-Verlag.

Author Keywords
Connectivity;  Functional MRI;  Hippocampus;  Prefrontal cortex;  Structural MRI;  Working memory

Document Type: Article
Source: Scopus

Vellimana, A.K.a , Kadkhodayan, Y.b , Rich, K.M.a b , Cross III, D.T.a b , Moran, C.J.a b , Zazulia, A.R.b c , Lee, J.-M.c , Chicoine, M.R.a , Dacey Jr., R.G.a , Derdeyn, C.P.a b c , Zipfel, G.J.a c
Symptomatic patients with intraluminal carotid artery thrombus: Outcome with a strategy of initial anticoagulation - Clinical article
(2013) Journal of Neurosurgery, 118 (1), pp. 34-41. 

a Department of Neurological Surgery, Washington University School of Medicine, St. Louis, MO, United States
b Department of Neurology, Washington University School of Medicine, St. Louis, MO, United States
c Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO, United States

Abstract
Object. The aim of this study was to define the optimal treatment for patients with symptomatic intraluminal carotid artery thrombus (ICAT). Methods. The authors performed a retrospective chart review of patients who had presented with symptomatic ICAT at their institution between 2001 and 2011. Results. Twenty-four patients (16 males and 8 females) with ICAT presented with ischemic stroke (18 patients) or transient ischemic attack ([TIA], 6 patients). All were initially treated using anticoagulation with or without antiplatelet drugs. Eight of these patients had no or only mild carotid artery stenosis on initial angiography and were treated with medical management alone. The remaining 16 patients had moderate or severe carotid stenosis on initial angiography; of these, 10 underwent delayed revascularization (8 patients, carotid endarterectomy [CEA]; 2 patients, angioplasty and stenting), 2 refused revascularization, and 4 were treated with medical therapy alone. One patient had multiple TIAs despite medical therapy and eventually underwent CEA; the remaining 23 patients had no TIAs after treatment. No patient suffered ischemic or hemorrhagic stroke while on anticoagulation therapy, either during the perioperative period or in the long-term follow-up; 1 patient died of an unrelated condition. The mean follow-up was 16.4 months. Conclusions. Results of this study suggest that initial anticoagulation for symptomatic ICAT leads to a low rate of recurrent ischemic events and that carotid revascularization, if indicated, can be safely performed in a delayed manner. ©AANS, 2013.

Author Keywords
Anticoagulation;  Carotid artery stenting;  Carotid artery thrombus;  Carotid endarterectomy;  Vascular disorders

Document Type: Article
Source: Scopus

Fritz, D.J.a , Carney, R.M.b , Steinmeyer, B.b , Ditson, G.c , Hill, N.a , Zee-Cheng, J.a
The efficacy of auriculotherapy for smoking cessation: A randomized, placebo-controlled trial
(2013) Journal of the American Board of Family Medicine, 26 (1), pp. 61-70. Cited 1 time.

a Veteran's Administration, Washington University, St. Louis, MO, United States
b Department of Psychiatry, Washington University, St. Louis, MO, United States

Abstract
Background: Quitting smoking remains a challenge for almost one-third of the military veteran population. Alternatives to pharmacological therapies such as acupuncture, acupressure, and electrical stimulation have received minimal attention in research but have been widely reported to be popular and safe interventions for smoking cessation. Methods: This randomized, double-blind, placebo-controlled clinical trial of 125 veterans was conducted to determine whether aural electrical stimulation (auriculotherapy) once a week for 5 consecutive weeks is associated with a higher rate of smoking abstinence are than observed with sham stimulation. Results: Auriculotherapy was found to be safe and largely free from significant side effects. However, there was no difference in the rate of smoking cessation between those participants who received true auriculotherapy and those who received sham auriculotherapy. The auriculotherapy group achieved a rate of 20.9% abstinence versus 17.9% for the placebo arm after 6 weeks. Conclusion: The results of this randomized, controlled clinical trial do not support the use of auriculotherapy to assist with smoking cessation. It is possible that a longer treatment duration, more frequent sessions, or other modifications of the intervention protocol used in this study may result in a different outcome. However, based on the results of this study, there is no evidence that auriculotherapy is superior to placebo when offered once a week for 5 weeks, as described in previous uncontrolled studies.

Author Keywords
Alternative medicine;  Tobacco cessation;  Veterans

Document Type: Article
Source: Scopus

Turpie, A.G.G.a , Hull, R.D.b , Schellong, S.M.c , Tapson, V.F.d , Monreal, M.e , Samama, M.-M.f , Chen, M.g , Yusen, R.D.h
Venous thromboembolism risk in ischemic stroke patients receiving extended-duration enoxaparin prophylaxis: Results from the EXCLAIM study
(2013) Stroke, 44 (1), pp. 249-251. 

 

a Department of Medicine, McMaster University, Hamilton Health Sciences-General Hospital, 237 Barton Street East, Hamilton, ON L8L 2X2, Canada
b University of Calgary, Foothills Hospital, Calgary, AB, Canada
c Municipal Hospital Dresden Friedrichstadt, Dresden, Germany
d Duke University Medical Center, Durham, NC, United States
e Hospital Germans Trias i Pujol, Barcelona, Spain
f Service d'Hématologie Biologique Hôtel-Dieu, Paris, France
g Sanofi-aventis, Bridgewater, NJ, United States
h Washington University School of Medicine, St. Louis, MO, United States

Abstract
Background and Purpose-: The optimal duration of venous thromboembolism prophylaxis in acute stroke patients is unknown. This subanalysis of the Extended Prophylaxis for Venous ThromboEmbolism in Acutely Ill Medical Patients With Prolonged Immobilization (EXCLAIM) study investigated extended-duration thromboprophylaxis with enoxaparin, compared with placebo following standard-duration enoxaparin, in ischemic stroke patients. Methods-: Acutely ill medical patients with recently reduced mobility received open-label enoxaparin 40 mg for 10±4 days, and they were then randomized to double-blind enoxaparin 40 mg daily or placebo for further 28±4 days. Venous thromboembolism incidence (symptomatic/asymptomatic deep-vein thrombosis, symptomatic/fatal pulmonary embolism) up to day 28 after randomization and major bleeding rates up to 48 h after the last dose of study treatment were reported. Results-: In total, 389 of 5963 (6.5%) randomized patients had ischemic stroke: 198 received extended-duration prophylaxis and 191 placebo. Extended-duration prophylaxis reduced venous thromboembolism incidence versus placebo (2.4% versus 8.0%; absolute risk difference,-5.6%; 95% CI,-10.5% to-0.7%), but it was associated with an increase in major bleeding (1.5% versus 0% in enoxaparin and placebo groups; absolute risk difference, +1.5%; 95% CI,-0.2% to 3.2%). CONCLUSION-: Extended-duration thromboprophylaxis with enoxaparin was associated with reduced venous thromboembolism risk and increased major bleeding in the subgroup of patients with ischemic stroke in the EXCLAIM study. Clinical Trial Registration INFORMATION-: URL: http://clinicaltrials.gov. Unique Identifier: NCT00077753. © 2012 American Heart Association, Inc.

Author Keywords
anticoagulants;  cerebrovascular disease/stroke;  deep-vein thrombosis

Document Type: Article
Source: Scopus

Jarvandi, S.a , Davidson, N.O.b c , Jeffe, D.B.a c , Schootman, M.a c
Influence of lifestyle factors on inflammation in men and women with type 2 diabetes: Results: From the national health and nutrition examination survey, 1999-2004
(2012) Annals of Behavioral Medicine, 44 (3), pp. 399-407. 

a Division of Health Behavior Research, Washington University School of Medicine, 4444 Forest Park Blvd., Saint Louis, MO 63108, United States
b Division of Gastroenterology, Washington University School of Medicine, Saint Louis, MO, United States
c Alvin J. Siteman Cancer Center, Barnes-Jewish Hospital, Washington University School of Medicine, Saint Louis, MO, United States

Abstract
Background: Type 2 diabetes is associated with low-grade systemic inflammation, increasing the risk for various adverse health outcomes. Purpose: Our objective was to investigate the association between C-reactive protein (CRP), a marker for systemic inflammation, and lifestyle factors in a national sample of people with type 2 diabetes. Methods: This study analyzed data from 1,086 men and women with diabetes, who completed the 1999-2004 NHANES. Lifestyle factors included diet quality, body mass index (BMI), smoking, and physical activity. Results: Stratified logistic regression showed that for both men and women, BMI was a strong predictor of elevated CRP after adjusting for age, energy intake, race/ethnicity, medications, diabetes duration, and glycosylated hemoglobin. However, among men, but not among women, the likelihood of elevated CRP increased with lower diet quality and physical inactivity. Conclusions: Among people with type 2 diabetes, higher levels of CRP were associated with lower diet quality and physical inactivity among men, and with obesity among both men and women. © The Society of Behavioral Medicine 2012.

Author Keywords
C-reactive protein;  Inflammation;  Lifestyle;  Type 2 diabetes

Document Type: Article
Source: Scopus

Parish, S.L.a , Thomas, K.C.b , Rose, R.b , Kilany, M.b , Shattuck, P.T.c
State medicaid spending and financial burden of families raising children with autism
(2012) Intellectual and Developmental Disabilities, 50 (6), pp. 441-451. 

a Lurie Institute for Disability Policy, Heller School for Social Policy and Management, Brandeis University, 415 South Street, MS 035, Waltham, MA 02454, United States
b University of North Carolina, Chapel Hill, NC, United States
c Washington University, St. Louis, WA, United States

Abstract
We examined the association between state Medicaid spending for children with disabilities and the financial burden reported by families of children with autism. Child and family data were from the 2005-2006 National Survey of Children with Special Health Care Needs (n 5 2,011 insured children with autism). State characteristics were from public sources. The 4 outcomes included any out-ofpocket health care expenditures during the past year, expenditure amount, expenditures as a proportion of family income, and whether additional income was needed to care for a child. We modeled the association between state per capita Medicaid spending for children with disabilities and families' financial burden, controlling for child, family, and state characteristics. Overall, 78%of families raising children with autism had health care expenditures for their child for the prior 12months; 42%reported expenditures over $500, with 34% spending over 3% of their income. Families living in states with higher per capitaMedicaid spending for children with disabilities were significantly less likely to report financial burden. There is a robust relationship between state Medicaid spending for children with disabilities and the financial burdens incurred by families raising children with autism. © AAIDD.

Author Keywords
Autism;  Cost of illness;  Health expenditures;  Medicaid

Document Type: Article
Source: Scopus

Saccone, N.L., Neuman, R.J., Saccone, S.F., Rice, J.P.
Genetic analysis of maximum cigarette-use phenotypes.
(2003) BMC genetics, 4 Suppl 1, art. no. S105, . Cited 24 times.

Department of Genetics, Washington University School of Medicine, St, Louis, Missouri, USA.

Abstract
Using the Framingham Heart Study data set provided for Genetic Analysis Workshop 13, we defined the cigarette-use phenotype M for smokers to be the maximum number of cigarettes-per-day (MAXCIG) reported over the longitudinal course of the study. Adjustments were made for the significant covariates of gender and year of birth, and sib-pair based linkage analysis was performed. The primary analyses, in which individuals with MAXCIG = 0 were considered to have missing phenotype, resulted in modest linkage evidence, with LOD scores over 1 on chromosomes 5, 9, 13, 14, and 22. While the results reported here do not indicate definitive evidence for linkage to specific chromosomal regions, future studies may find it useful to include direct assessments of maximum and quantitative cigarette use. In defining and analyzing quantitative or "maximum use" phenotypes, the choice of how to handle individuals with MAXCIG = 0, or alternatively, individuals who are substance-naive, is a crucial one for genetic studies of nicotine and other substance use. In this study, the linkage results vary greatly depending on whether or not these "unexposed" individuals are included in the analyses.

Document Type: Article
Source: Scopus

 

January 17, 2013

Cohen-Shikora, E.R., Balota, D.A.
Past tense route priming 
(2013) Cognition, 126 (3), pp. 397-404. 

Department of Psychology, Washington University in St. Louis, United States

Abstract
The present research examined whether lexical (whole word) or more rule-based (morphological constituent) processes can be locally biased by experimental list context in past tense verb inflection. In Experiment 1, younger and older adults completed a past tense inflection task in which list context was manipulated across blocks containing regular past tense verbs (e.g. REACH-REACHED) or irregular past tense verbs (TEACH-TAUGHT). Critical targets, consisting of half regular and half irregular verbs, were embedded within blocks and participants' inflection response latency and accuracy were assessed. The results yielded a cross-over interaction in response latencies for both young and older adults. In the regular context there was a robust regularity effect: regular target verbs were conjugated faster than irregular target verbs. In contrast, in the irregular context, irregular target verbs were conjugated faster than regular target verbs. Experiment 2 used the same targets but in the context of either standard nonwords or nonwords ending in "-ED" to test the possibility of a phonological basis for the effect. The effect of context was eliminated. The results support the notion that distinct processes in past tense verb production can be locally biased by list context and, as shown in Experiment 2, this route priming effect was not due to phonological priming. © 2012 Elsevier B.V.

Author Keywords
Past tense inflection;  Pathway priming

Document Type: Article
Source: Scopus

  

Al-Kateb, H.a , Shimony, J.S.b , Vineyard, M.c , Manwaring, L.c , Kulkarni, S.a , Shinawi, M.c 
NR2F1 haploinsufficiency is associated with optic atrophy, dysmorphism and global developmental delay 
(2013) American Journal of Medical Genetics, Part A, . Article in Press. 

a Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri
b Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, Missouri
c Department of Pediatrics, Division of Genetics and Genomic Medicine, Washington University School of Medicine, St. Louis, Missouri
 
Document Type: Article in Press

Source: Scopus

 

Peng, G.-H.a , Chen, S.a b 
Double chromatin immunoprecipitation: Analysis of target co-occupancy of retinal transcription factors 
(2013) Methods in Molecular Biology, 935, pp. 311-328. 

a Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis MO, United States
b Department of Developmental Biology, Washington University School of Medicine, St. Louis MO, United States

Abstract
Combinatorial binding of transcription factors (TFs) and cofactors to specific regulatory regions of target genes in vivo is an important mechanism of transcriptional regulation. Chromatin immunoprecipitation (ChIP) is a powerful technique to detect protein binding to specific regions of target genes in vivo. However, conventional ChIP analysis for individual factors (single ChIP) does not provide information on co-occupancy of two interacting TFs on target genes, even if both bind to the same chromatin regions. Double ChIP analysis involves sequential (double) immunoprecipitation of two chromatin-binding proteins and can be used to study co-occupancy of two or more factors on specific regions of the same DNA allele. Furthermore, by including a cell type-specific protein in double-ChIP, target co-occupancy in a specific cell type can be studied even if the other partner is more widely expressed. In this chapter, we describe a detailed protocol for double ChIP analysis in mouse retinas. Using the rod-specific transcription factor NR2E3 and the cone/rod homeobox protein CRX as examples, we show that NR2E3 and CRX are co-enriched on the promoter of active Rho and Rbp3 genes in rods, but are present to a much lesser degree on the promoters of silent cone opsin genes. These results suggest a new mechanism by which rod and cone genes are differentially regulated by these transcription factors in rod photoreceptors. © 2013 Springer Science+Business Media, LLC.

Author Keywords
Double chromatin immunoprecipitation;  Retinal photoreceptors;  Target co-occupancy;  Transcription factor interactions


Document Type: Article
Source: Scopus

 

Montana, C.L., Myers, C.A., Corbo, J.C.
Quantifying the Activity of cis-Regulatory Elements in the Mouse Retina by Explant Electroporation 
(2013) Methods in Molecular Biology, 935, pp. 329-340.  

Department of Pathology and Immunology, Washington University School of Medicine, St. Louis MO, United States

Abstract
Transcription factors control gene expression by binding to noncoding regions of DNA known as  cis-regulatory elements (CREs i.e., enhancer/promoters). Traditionally, cis-regulatory analysis has been carried out via mouse transgenesis which is time1-consuming and nonquantitative. Electroporation of DNA reporter constructs into living mouse tissue is a rapid and effective alternative to transgenesis which permits quantitative assessment of cis-regulatory activity. Here, we present a simple technique for quantifying the activity of photoreceptor-specific CREs in living explanted mouse retinas. © 2013 Springer Science+Business Media, LLC.

Author Keywords
cis-Regulatory element;  Electroporation;  Mouse;  Photoreceptor;  Quantification;  Retina


Document Type: Article
Source: Scopus

 

Ragan, D.K.a , McKinstry, R.b , Benzinger, T.b , Leonard, J.R.c , Pineda, J.A.a 
Alterations in cerebral oxygen metabolism after traumatic brain injury in children 
(2013) Journal of Cerebral Blood Flow and Metabolism, 33 (1), pp. 48-52. 

a Department of Pediatrics and Neurology, Division of Critical Care Medicine, Washington University School of Medicine, One Children's Place, St Louis, MO 63110, United States
b Department of Radiology, Washington University School of Medicine, St Louis, MO, United States
c Department of Neurosurgery, Washington University School of Medicine, St Louis, MO, United States

Abstract
Traumatic brain injury (TBI) is the most common cause of acquired disability in children. Metabolic defects, and in particular mitochondrial dysfunction, are important contributors to brain injury after TBI. Studies of metabolic dysfunction are limited, but magnetic resonance methods suitable for use in children are overcoming this limitation. We performed noninvasive measurements of cerebral blood flow and oxygen metabolic index (OMI) to assess metabolic dysfunction in children with severe TBI. Cerebral blood flow is variable after TBI but hypoperfusion and low OMI are predominant, supporting metabolic dysfunction. This finding is consistent with preclinical and adult clinical studies of brain metabolism and mitochondrial dysfunction after TBI. © 2013 ISCBFM All rights reserved.

Author Keywords
brain imaging;  brain trauma;  cerebral blood flow


Document Type: Article
Source: Scopus

 

Su, Y.a , Arbelaez, A.M.b , Benzinger, T.L.S.a , Snyder, A.Z.a , Vlassenko, A.G.a , Mintun, M.A.c , Raichle, M.E.a 
Noninvasive estimation of the arterial input function in positron emission tomography imaging of cerebral blood flow 
(2013) Journal of Cerebral Blood Flow and Metabolism, 33 (1), pp. 115-121. 

a Department of Radiology, Mallinckrodt Institute of Radiology, Washington University School of Medicine, 510 South Kingshighway Boulevard, St Louis, MO 63110, United States
b Department of Pediatrics, Washington University School of Medicine, St Louis, MO, United States
c Avid Radiopharmaceuticals, Philadelphia, PA, United States

Abstract
Positron emission tomography (PET) with 15 O-labeled water can provide reliable measurement of cerebral blood flow (CBF). Quantification of CBF requires knowledge of the arterial input function (AIF), which is usually provided by arterial blood sampling. However, arterial sampling is invasive. Moreover, the blood generally is sampled at the wrist, which does not perfectly represent the AIF of the brain, because of the effects of delay and dispersion. We developed and validated a new noninvasive method to obtain the AIF directly by PET imaging of the internal carotid artery in a region of interest (ROI) defined by coregistered high-resolution magnetic resonance angiography. An ROI centered at the petrous portion of the internal carotid artery was defined, and the AIF was estimated simultaneously with whole brain blood flow. The image-derived AIF (IDAIF) method was validated against conventional arterial sampling. The IDAIF generated highly reproducible CBF estimations, generally in good agreement with the conventional technique. © 2013 ISCBFM All rights reserved.

Author Keywords
arterial input function;  PET

Document Type: Article
Source: Scopus

 

Zhu, Y.a , Zhang, L.a , Sasaki, Y.b , Milbrandt, J.b , Gidday, J.M.a c d 
Protection of mouse retinal ganglion cell axons and soma from glaucomatous and ischemic injury by cytoplasmic overexpression of Nmnat1 
(2013) Investigative Ophthalmology and Visual Science, 54 (1), pp. 25-36. 

a Department of Neurosurgery, AHAF National Glaucoma Foundation, NIH EY18607, United States
b Department of Genetics, Department of Ophthalmology, Washington University, The ALS Foundation, AG13730, United States
c Department of Ophthal-mology and Visual Sciences, Washington University School of Medicine, St. Louis, MO, United States
d Department of Cell Biology and Physiology, Washington University School of Medicine, AHAF National Glaucoma Foundation, St. Louis, NIH EY18607, MO, United States

Abstract
Purpose. The Wlds mutation affords protection of retinal ganglion cell (RGC) axons in retinal ischemia and in inducible and hereditary preclinical models of glaucoma. We undertook the present study to determine whether the Nmnat1 portion of the chimeric protein provides axonal and somatic protection of RGCs in models of ischemia and glaucoma, particularly when localized to nonnuclear regions of the cell. Methods. The survival and integrity of RGC axons and soma from transgenic mice with confirmed cytoplasmic overexpres-sion of Nmnat1 in retina and optic nerve (cytNmnat1-Tg mice) were examined in the retina and postlaminar optic nerve 4 days following acute retinal ischemia, and 3 weeks following the chronic elevation of intraocular pressure. Results. Ischemia- and glaucoma-induced disruptions of proximal segments of RGC axons that comprise the nerve fiber layer in wild-type mice were both robustly abrogated in cytNmnat1-Tg mice. More distal portions of RGC axons within the optic nerve were also protected from glaucomatous disruption in the transgenic mice. In both disease models, Nmnat1 overexpression in extranuclear locations significantly enhanced the survival of RGC soma. Conclusions. Overexpression of Nmnat1 in the cytoplasm and axons of RGCs robustly protected against both ischemic and glaucomatous loss of RGC axonal integrity, as well as loss of RGC soma. These findings reflect the more pan-cellular protection of CNS neurons that is realized by cytoplasmic Nmnat1 expression, and thus provide a therapeutic strategy for protecting against retinal neurodegeneration, and perhaps other CNS neurodegenerative diseases as well. © 2013 The Association for Research in Vision and Ophthalmology, Inc.
 

Document Type: Article
Source: Scopus

 

Holmes, B.B., Diamond, M.I.
Amyotrophic lateral sclerosis and organ donation: Is there risk of disease transmission? 
(2012) Annals of Neurology, 72 (6), pp. 832-836. 

Department of Neurology, School of Medicine, Washington University in St Louis, 4559 Scott Ave, St Louis, MO 63110, United States

Abstract
A new protocol suggests that patients with amyotrophic lateral sclerosis (ALS) are a viable source of tissue for organ transplantation. However, multiple lines of evidence suggest that many neurodegenerative diseases, including ALS, might progress due to transcellular propagation of protein aggregation among neurons. Transmission of the disease state from donor to host thus may be possible under the permissive circumstances of graft transplantation. We argue for careful patient selection and close longitudinal follow-up of recipients when harvesting organs from individuals with neurodegenerative disease, especially dominantly inherited forms. Copyright © 2012 American Neurological Association.
 

Document Type: Review
Source: Scopus

 

Cho, H.a , Diamond, M.S.a b c 
Immune responses to west nile virus infection in the central nervous system 
(2012) Viruses, 4 (12), pp. 3812-3830. 

a Departments of Molecular Microbiology, Washington University School of Medicine, St. Louis, MI 63110, United States
b Departments of Medicine, Washington University School of Medicine, St. Louis, MI 63110, United States
c Pathology and Immunology, Washington University School of Medicine, St. Louis, MI 63110, United States

Abstract
West Nile virus (WNV) continues to cause outbreaks of severe neuroinvasive disease in humans and other vertebrate animals in the United States, Europe, and other regions of the world. This review discusses our understanding of the interactions between virus and host that occur in the central nervous system (CNS), the outcome of which can be protection, viral pathogenesis, or immunopathogenesis. We will focus on defining the current state of knowledge of WNV entry, tropism, and host immune response in the CNS, all of which affect the balance between injury and successful clearance. © 2012 by the authors; licensee MDPI, Basel, Switzerland.

Author Keywords
Adaptive immunity;  Brain;  Flavivirus;  Immunopathogenesis;  Innate immunity;  Neuron;  Pathogenesis


Document Type: Review
Source: Scopus

 

Kim, J.a b c , Eltorai, A.E.Ma b c , Jiang, H.a b c , Liao, F.a b c , Verghese, P.B.a b c , Kim, J.a b c , Stewart, F.R.a b c , Basak, J.M.a bc , Holtzman, D.M.a b c 
Anti-apoE immunotherapy inhibits amyloid accumulation in a transgenic mouse model of Aβ amyloidosis 
(2012) Journal of Experimental Medicine, 209 (12), pp. 2149-2156. 

a Department of Neurology, Washington University School of Medicine, Saint Louis, MO 63110, United States
b Hope Center for Neurological Disorders, Washington University School of Medicine, Saint Louis, MO 63110, United States
c Knight Alzheimer's Disease Research Center, Washington University School of Medicine, Saint Louis, MO 63110, United States

Abstract
The apolipoprotein E (APOE) E{open}4 allele is the strongest genetic risk factor for Alzheimer's disease (AD). The influence of apoE on amyloid β (Aβ) accumulation may be the major mechanism by which apoE affects AD. ApoE interacts with Aβ and facilitates Aβ fibrillogenesis in vitro. In addition, apoE is one of the protein components in plaques. We hypothesized that certain anti-apoE antibodies, similar to certain anti-Aβ antibodies, may have antiamyloidogenic effects by binding to apoE in the plaques and activating microglia-mediated amyloid clearance. To test this hypothesis, we developed several monoclonal anti-apoE antibodies. Among them, we administered HJ6.3 antibody intraperitoneally to 4-mo-old male APPswe/PS1ΔE9 mice weekly for 14 wk. HJ6.3 dramatically decreased amyloid deposition by 60-80% and significantly reduced insoluble Aβ40 and Aβ42 levels. Short-term treatment with HJ6.3 resulted in strong changes in microglial responses around Aβ plaques. Collectively, these results suggest that anti-apoE immunization may represent a novel AD therapeutic strategy and that other proteins involved in Aβ binding and aggregation might also be a target for immunotherapy. Our data also have important broader implications for other amyloidosis. Immunotherapy to proteins tightly associated with misfolded proteins might open up a new treatment option for many protein misfolding diseases. © 2012 Kim et al.
 

Document Type: Article
Source: Scopus

 

Wineland, A.M., Burton, H., Piccirillo, J.
Functional connectivity networks in nonbothersome tinnitus. 
(2012) Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery, 147 (5), pp. 900-906. 

Department of Otolaryngology-Head & Neck Surgery, Washington University School of Medicine, St Louis, MO, USA.

Abstract
To assess functional connectivity in cortical networks in patients with nonbothersome tinnitus compared with a normal healthy nontinnitus control group by measuring low-frequency (<0.1 Hz) spontaneous blood oxygenation level-dependent (BOLD) signals at rest. Case-control. Academic medical center. Nonbothersome, idiopathic subjective tinnitus for at least 6 months (n = 18) and a normal healthy nontinnitus control group (n = 23). Functional connectivity differences in 58 a priori selected seed regions of interest encompassing cortical loci in the default mode, attention, auditory, visual, somatosensory, and cognitive networks. The median age of the 18 subjects was 54 years (interquartile range [IQR], 52-57), 66% were male, 90% were white, median Tinnitus Handicap Inventory (THI) score was 8 (IQR, 4-14), and a median Beck Depression Index score was 1 (IQR, 0-5). The median age for the control group was 46 years (IQR, 39-54), and 52% were male. Of the 58 seeds analyzed, no regions had significantly different functional connectivity among the nonbothersome tinnitus group when compared with the control group. Among nonbothersome tinnitus patients, the tinnitus percept does not appear to alter the functional connectivity of the auditory cortex or other key cortical regions. Trial Registration ClinicalTrials.gov Identifier: NCT01049828.
 


Document Type: Article
Source: Scopus

 

Merlo, L.J., Cummings, S.M., Cottler, L.B.
Recovering substance-impaired pharmacists' views regarding occupational risks for addiction. 
(2012) Journal of the American Pharmacists Association : JAPhA, 52 (4), pp. 480-491. 

School of Medicine, Washington University, St. Louis, MO, USA.

Abstract
To better understand the occupational risks for substance use disorders among pharmacists and possibilities for improved prevention. Descriptive, nonexperimental, cross-sectional study. A southeastern state from December 2008 to April 2009. 32 participants (72.7% men) from the impaired professionals monitoring groups in the geographic regions within the state that had the greatest number of physicians, pharmacists, and allied health professionals currently under monitoring contracts for substance use disorders. Guided group discussions regarding substance use among health care providers. Persistent occupational risks for development of a substance use disorder among pharmacists. Several occupational hazards unique to the pharmacy profession might contribute to the problem of substance use disorders among some members of this population, including increased access to potent drugs of abuse, a stressful/unpleasant working environment, a culture that unofficially condones medication diversion, lack of education related to addiction, and lack of support for individuals seeking treatment. These results have important implications for the education of student pharmacists, the continuing education of licensed pharmacists, and the management of pharmacies in which these individuals work. Given the potential occupational risks for substance abuse associated with the pharmacy profession, additional training, monitoring, changes to the work environment, and increased confidential access to treatment may be needed to safeguard pharmacy professionals and the communities they serve.
 
Document Type: Article
Source: 
Scopus

 

January 10, 2013

Sheline, Y.I., Raichle, M.E.
Resting State Functional Connectivity in Preclinical Alzheimer's Disease
(2013) Biological Psychiatry, . Article in Press. 

Departments of Psychiatry, Radiology, and Neurology (YIS); and Departments of Radiology, Neurology, Neurobiology and Biomedical Engineering (MER), Washington University School of Medicine, St. Louis, Missouri

Abstract
There has been a dramatic increase in the number of studies using resting state functional magnetic resonance imaging (rs-fMRI), a recent addition to imaging analysis techniques. The technique analyzes ongoing low-frequency fluctuations in the blood oxygen level-dependent signal. Through patterns of spatial coherence, these fluctuations can be used to identify the networks within the brain. Multiple brain networks are present simultaneously, and the relationships within and between networks are in constant dynamic flux. Resting state fMRI functional connectivity analysis is increasingly used to detect subtle brain network differences and, in the case of pathophysiology, subtle abnormalities in illnesses such as Alzheimer's disease (AD). The sequence of events leading up to dementia has been hypothesized to begin many years or decades before any clinical symptoms occur. Here we review the findings across rs-fMRI studies in the spectrum of preclinical AD to clinical AD. In addition, we discuss evidence for underlying preclinical AD mechanisms, including an important relationship between resting state functional connectivity and brain metabolism and how this results in a distinctive pattern of amyloid plaque deposition in default mode network regions. © 2012 Society of Biological Psychiatry.

Author Keywords
Amyloid;  BOLD;  default mode network (DMN);  fMRI;  glycolysis;  precuneus

Document Type: Article in Press
Source: Scopus

 

Laryea, G.a c , Arnett, M.G.b c , Wieczorek, L.d , Muglia, L.J.b c 
Site-specific modulation of brain glucocorticoid receptor and corticotropin-releasing hormone expression using lentiviral vectors
(2013) Molecular and Cellular Endocrinology, . Article in Press. 

a Neuroscience Graduate Program, School of Medicine, Vanderbilt University, 465 21st. Avenue South, Nashville, TN 37232, USA
b Department of Pediatrics, University of Cincinnati College of Medicine, 3333 Burnet Avenue, Cincinnati, OH 45229, USA
c Center for Prevention of Preterm Birth, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229, USA
d Program in Neuroscience, Washington University, 660 S. Euclid, St. Louis, MO 63110, USA

Abstract
The glucocorticoid receptor (GR) and corticotropin-releasing hormone (CRH) are important molecular regulators of an individual's ability to respond to stressful stimuli in an adaptive manner. Impaired signaling of both GR and CRH often leads to dysfunction of the hypothalamic-pituitary-adrenal axis, which underlies the etiology of many affective disorders such as anxiety and depression. Studies focusing on how GR and CRH influence the stress response are limited as they generalize to broad brain regions, thus hindering identification of how specific CNS nuclei contribute to maladaptive stress responses. Our objective is to distinguish the site-specific involvement of GR and CRH in limbic regions involved in the stress response. With that intent, we use lentiviral (LV) vectors in combination with transgenic mouse lines, enabling us to modify expression of GR or CRH in a very localized manner. This paper describes the generation of several distinct LV vectors and transgenic mice models that will help further elucidate the site-specific actions of GR and CRH. © 2012 Elsevier Ireland Ltd. All rights reserved.

Author Keywords
Corticotropin-releasing hormone;  Glucocorticoid receptor;  Hypothalamic-pituitary-adrenal axis;  Lentiviral vectors;  Psychiatric disorders;  Stress

Document Type: Article in Press
Source: Scopus

 

Dimaras, H.a b c d , Parulekar, M.V.e f , Kwok, G.a b , Simpson, E.R.c , Ali, A.b e , Halliday, W.g, Shago, M.h , Harbour, J.W.i , Héon, E.e , Gallie, B.L.c d j k l , Chan, H.S.L.a b 
Molecular testing prognostic of low risk in epithelioid uveal melanoma in a child
(2013) British Journal of Ophthalmology, . Article in Press. 

a Division of Hematology/Oncology, The Hospital for Sick Children, Toronto, Ontario, Canada
b Department of Paediatrics, The Hospital for Sick Children, Toronto, Ontario, Canada
c Department of Ophthalmology and Vision Sciences, University of Toronto, Toronto, Ontario, Canada
d The Divisions of Visual Science, University Health Network, University of Toronto, Toronto, Ontario, Canada
e Department of Ophthalmology and Vision Sciences, The Hospital for Sick Children, Toronto, Ontario, Canada
f Birmingham Children's Hospital, Birmingham, UK
g Department of Pathology, The Hospital for Sick Children, Toronto, Ontario, Canada
h Department of Cytogenetics, The Hospital for Sick Children, Toronto, Ontario, Canada
i Siteman Comprehensive Cancer Center, Washington University School of Medicine, St. Louis, Missouri, USA
j Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada
k Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada
l Applied Molecular Oncology, University Health Network, University of Toronto, Toronto, Ontario, Canada

Abstract
Aims: To characterise a histologically unusual paediatric uveal melanoma by gene expression and karyotypic profiling and assess prognosis. Methods: The tumour was studied by histopathology, karyotype analysis, single nucleotide polymorphism and gene expression profile analysis for correlation with clinical outcome. Results: The tumour had predominantly epithelioid histology. Karyotype analysis showed none of the poor prognosis features normally associated with uveal melanoma. single nucleotide polymorphism analysis revealed no imbalance at chromosome 3. Gene expression profiling indicated low risk disease. Conclusions: We report a child remaining relapse-free 6 years after diagnosis of a very rare uveal melanoma, with poor prognosis epithelioid histology, but gene expression profiling that accurately predicted low risk disease. Copyright Article author (or their employer) 2013.

Document Type: Article in Press
Source: Scopus

 

Jimura, K.a b c , Chushak, M.S.c , Braver, T.S.c d 
Impulsivity and self-control during intertemporal decision making linked to the neural dynamics of reward value representation
(2013) Journal of Neuroscience, 33 (1), pp. 344-357. 

a Precision and Intelligence Laboratory, Tokyo Institute of Technology, Yokohama 226-8503, Japan
b Imaging Research Center, The University of Texas at Austin, Austin, TX 78712, United States
c Departments of Psychology, Washington University in St. Louis, St. Louis, MO 63130, United States
d Departments of Radiology, Washington University in St. Louis, St. Louis, MO 63130, United States

Abstract
A characteristic marker of impulsive decision making is the discounting of delayed rewards, demonstrated via choice preferences and choice-related brain activity. However, delay discounting may also arise from how subjective reward value is dynamically represented in the brain when anticipating an upcoming chosen reward. In the current study, brain activity was continuously monitored as human participants freely selected an immediate or delayed primary liquid reward and then waited for the specified delay before consuming it. The ventromedial prefrontal cortex (vmPFC) exhibited a characteristic pattern of activity dynamics during the delay period, as well as modulation during choice, that is consistent with the time-discounted coding of subjective value. The ventral striatum (VS) exhibited a similar activity pattern, but preferentially in impulsive individuals. A contrasting profile of delay-related and choice activation was observed in the anterior PFC (aPFC), but selectively in patient individuals. Functional connectivity analyses indicated that both vmPFC and aPFC exerted modulatory, but opposite, influences on VS activation. These results link behavioral impulsivity and self-control to dynamically evolving neural representations of future reward value, not just during choice, but also during postchoice delay periods. © 2013 the authors.

Document Type: Article
Source: Scopus

 

Pergadia, M.L.a , Gilbert, D.G.b 
Commentary on Etter etal. (2013): The ups and downs of nicotine withdrawal and methods to study the process
(2013) Addiction, 108 (1), pp. 60-61. 

a Department of Psychiatry, Washington University School of Medicine, St Louis, MO, United States
b Southern Illinois University-Carbondale, Carbondale, IL, United States

Author Keywords
Design;  Internet study;  Methods;  Nicotine withdrawal;  Smoking;  Symptoms

Document Type: Article
Source: Scopus

 

Lessov-Schlaggar, C.N.a , Lepore, R.L.b , Kristjansson, S.D.a , Schlaggar, B.L.b , Barnes, K.A.c , Petersen, S.E.b d , Madden, P.A.F.a , Heath, A.C.a , Barch, D.M.a d 
Functional neuroimaging study in identical twin pairs discordant for regular cigarette smoking
(2013) Addiction Biology, 18 (1), pp. 98-108. 

a Department of Psychiatry, Washington University School of Medicine, Campus Box 8134, 660 S. Euclid, Saint Louis, MO 63110, United States
b Department of Neurology, Washington University School of Medicine, St. Louis, MO, United States
c Laboratory of Brain and Cognition, National Institute of Mental Health, Bethesda, MD, United States
d Department of Psychology, Washington University, St. Louis, MO, United States

Abstract
Despite the tremendous public health and financial burden of cigarette smoking, relatively little is understood about brain mechanisms that subserve smoking behavior. This study investigated the effect of lifetime regular smoking on brain processing in a reward guessing task using functional magnetic resonance imaging and a co-twin control study design in monozygotic (MZ) twin pairs that maximally controls for genetic and family background factors. Young adult (24-34 years) MZ female twin pairs (n = 15 pairs), discordant for regular smoking defined using Centers for Disease Control criteria as having smoked â¥100 cigarettes in their lifetime, were recruited from an ongoing genetic epidemiological longitudinal study of substance use and psychopathology. We applied hypothesis-driven region of interest (ROI) and whole-brain analyses to investigate the effect of regular smoking on reward processing. Reduced response to reward and punishment in regular compared with never-regular smokers was seen in hypothesis-driven ROI analysis of bilateral ventral striatum. Whole-brain analysis identified bilateral reward-processing regions that showed activation differences in response to winning or losing money but no effect of regular smoking; and frontal/parietal regions, predominantly in the right hemisphere, that showed robust effect of regular smoking but no effect of winning or losing money. Altogether, using a study design that maximally controls for group differences, we found that regular smoking had modest effects on striatal reward processing regions but robust effects on cognitive control/attentional systems. © 2012 Society for the Study of Addiction.

Author Keywords
Cigarette smoking;  co-twin control;  cognitive control;  discordant;  fMRI;  reward

Document Type: Article
Source: Scopus

 

Tripodi, S.J.a , Pettus-Davis, C.b 
Histories of childhood victimization and subsequent mental health problems, substance use, and sexual victimization for a sample of incarcerated women in the US

(2013) International Journal of Law and Psychiatry, 36 (1), pp. 30-40. 

a Florida State University, College of Social Work, University Center C, 296 Champions Way, Tallahassee, FL 32306, United States
b Washington University in St. Louis, Brown School, Campus Box 1196, Goldfarb Hall, One Brookings Drive, St. Louis, MO 63130, United States

Abstract
Women are entering US prisons at nearly double the rate of men and are the fastest growing prison population. Current extant literature focuses on the prevalence of the incarceration of women, but few studies exist that emphasize the different trajectories to prison. For example, women prisoners have greater experiences of prior victimization, more reports of mental illness, and higher rates of illicit substance use. The purpose of this study was to understand the prevalence of childhood victimization and its association with adult mental health problems, substance abuse disorders, and further sexual victimization. The research team interviewed a random sample of 125 women prisoners soon to be released from prison to gather information on their childhood physical and sexual victimization, mental health and substance abuse problems as an adult, and sexual victimization in the year preceding incarceration. Results indicate that women prisoners in this sample, who were both physically and sexually victimized as children, were more likely to be hospitalized as an adult for a psychological or emotional problem. Women who were sexually victimized or both physically and sexually victimized were more likely to attempt suicide. Women who experienced physical victimization as children and women who were both physically and sexually victimized were more likely to have a substance use disorder and women who were sexually abused as children or both physically and sexually victimized were more likely to be sexually abused in the year preceding prison. This article ends with a discussion about prisons' role in providing treatment for women prisoners and basing this treatment on women's trajectories to prison, which disproportionately include childhood victimization and subsequent mental health and substance use problems. © 2012 Elsevier Ltd.

Author Keywords
Mental health;  Prisoners;  Substance abuse;  Victimization;  Women offenders

Document Type: Article
Source: Scopus

 

Xing, W.a b , Wang, L.a , Maslov, K.a , Wang, L.V.a b 
Integrated optical- and acoustic-resolution photoacoustic microscopy based on an optical fiber bundle
(2013) Optics Letters, 38 (1), pp. 52-54. 

a Optical Imaging Laboratory, Department of Biomedical Engineering, Washington University in St. Louis, One Brookings Drive, St. Louis, Missouri 63130, United States
b Preston M. Green Department of Electrical and Systems Engineering, Washington University in St. Louis, One Brookings Drive, St. Louis, Missouri 63130, United States

Abstract
Photoacoustic microscopy (PAM), whose spatial resolution and maximum imaging depth are both scalable, has made great progress in recent years. However, each PAM system currently achieves only one resolution with an associated maximum imaging depth. Here, we present an integrated optical-resolution (OR) and acousticresolution (AR) PAM system implemented by delivering light via an optical fiber bundle. A single fiber core is used to deliver light for OR illumination in order to achieve a small spot size and hence high lateral resolution, whereas all the fiber cores are used to deliver more energy for AR illumination. Most other components are shared by the OR and AR imaging. The lateral resolution can be seamlessly switched between 2.2 and 40 μmas the maximum imaging depth is switched between 1.3 and 3.0 mm. The system enables automatically coregistered higher-resolution OR and deeper AR photoacoustic imaging. © 2012 Optical Society of America.

Document Type: Article
Source: Scopus

 

Goyal, M.a , Menon, B.K.a , Derdeyn, C.P.b 
Perfusion imaging in acute ischemic stroke: Let us improve the science before changing clinical practice
(2013) Radiology, 266 (1), pp. 16-21. 

a Departments of Radiology and Clinical Neurosciences, Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada
b Mallinckrodt Institute of Radiology, Washington University School of Medicine, St Louis, MO, United States

Document Type: Note
Source: Scopus

 

Shoss, B.L., Tsai, L.M.
Postoperative care in cataract surgery
(2013) Current Opinion in Ophthalmology, 24 (1), pp. 66-73. 

Department of Ophthalmology and Visual Sciences, Washington University, 10 BarnesWest Drive, St. Louis, MO 63141, United States

Abstract
PURPOSE OF REVIEW: The purpose of this study is to provide a summary of current trends and recent developments in postoperative care after cataract surgery. RECENT FINDINGS: There is new evidence challenging the routine use of a protective eye shield after uncomplicated cataract surgery. Nonsteroidal anti-inflammatory drugs (NSAIDs) are effective in decreasing the risk of cystoid macular edema (CME) in high-risk eyes, but must be used with caution in patients with prior corneal disease. Pre-existing ocular comorbidities can have significant effects on postoperative outcomes. Management of postoperative visual expectations can be challenging in patients receiving newer advanced technology intraocular lenses (IOLs). SUMMARY: Key practices such as restrictions on activities, prophylactic regimens against infection and inflammation, appropriate follow-up with adjustments for individual risk factors and management of complications, and continuing care until visual rehabilitation is complete are advised to optimize visual outcome for patients after cataract surgery. © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Author Keywords
cataract surgery;  complications;  postoperative care

Document Type: Review
Source: Scopus

 

Anticevic, A.a , Repovs, G.b , Barch, D.M.c d e 
Working memory encoding and maintenance deficits in schizophrenia: Neural evidence for activation and deactivation abnormalities
(2013) Schizophrenia Bulletin, 39 (1), pp. 168-178. 

a Department of Psychiatry, Yale University, 34 Park Street, New Haven, CT 06519, United States
b Department of Psychology, University of Ljubljana, Ljubljana, Slovenia
c Department of Psychology, Washington University in St Louis, St Louis, MO, United States
d Department of Psychiatry, Washington University in St Louis, St Louis, MO, United States
e Department of Radiology, Washington University in St Louis, St Louis, MO, United States

Abstract
Substantial evidence implicates working memory (WM) as a core deficit in schizophrenia (SCZ), purportedly due to primary deficits in dorsolateral prefrontal cortex functioning. Recent findings suggest that SCZ is also associated with abnormalities in suppression of certain regions during cognitive engagement-namely the default mode system-that may further contribute to WM pathology. However, no study has systematically examined activation and suppression abnormalities across both encoding and maintenance phases of WM in SCZ. Twenty-eight patients and 24 demographically matched healthy subjects underwent functional magnetic resonance imaging at 3T while performing a delayed match-to-sample WM task. Groups were accuracy matched to rule out performance effects. Encoding load was identical across subjects to facilitate comparisons across WM phases. We examined activation differences using an assumed model approach at the whole-brain level and within meta-analytically defined WM areas. Despite matched performance, we found regions showing less recruitment during encoding and maintenance for SCZ subjects. Furthermore, we identified 2 areas closely matching the default system, which SCZ subjects failed to deactivate across WM phases. Lastly, activation in prefrontal regions predicted the degree of deactivation for healthy but not SCZ subjects. Current results replicate and extend prefrontal recruitment abnormalities across WM phases in SCZ. Results also indicate deactivation abnormalities across WM phases, possibly due to inefficient prefrontal recruitment. Such regional deactivation may be critical for suppressing sources of interference during WM trace formation. Thus, deactivation deficits may constitute an additional source of impairments, which needs to be further characterized for a complete understanding of WM pathology in SCZ. © 2011 The Author.

Author Keywords
default network;  encoding;  fMRI;  maintenance;  schizophrenia;  working memory

Document Type: Article
Source: Scopus

 

Woodward, L.J.a b , Clark, C.A.C.c , Bora, S.a , Inder, T.E.d 
Neonatal White Matter Abnormalities an Important Predictor of Neurocognitive Outcome for Very Preterm Children

 

 

(2012) PLoS ONE, 7 (12), art. no. e51879, . 

a Canterbury Child Development Research Group, Department of Psychology, University of Canterbury, Christchurch, New Zealand
b New Zealand Brain Research Institute, Christchurch, New Zealand
c Department of Psychology, University of Oregon, Eugene, OR, United States
d Departments of Pediatrics, Neurology and Radiology, Washington University School of Medicine, St Louis, MO, United States

Abstract
Background: Cerebral white matter abnormalities on term MRI are a strong predictor of motor disability in children born very preterm. However, their contribution to cognitive impairment is less certain. Objective: Examine relationships between the presence and severity of cerebral white matter abnormalities on neonatal MRI and a range of neurocognitive outcomes assessed at ages 4 and 6 years. Design/Methods: The study sample consisted of a regionally representative cohort of 104 very preterm (≤32 weeks gestation) infants born from 1998-2000 and a comparison group of 107 full-term infants. At term equivalent, all preterm infants underwent a structural MRI scan that was analyzed qualitatively for the presence and severity of cerebral white matter abnormalities, including cysts, signal abnormalities, loss of white matter volume, ventriculomegaly, and corpus callosal thinning/myelination. At corrected ages 4 and 6 years, all children underwent a comprehensive neurodevelopmental assessment that included measures of general intellectual ability, language development, and executive functioning. Results: At 4 and 6 years, very preterm children without cerebral white matter abnormalities showed no apparent neurocognitive impairments relative to their full-term peers on any of the domain specific measures of intelligence, language, and executive functioning. In contrast, children born very preterm with mild and moderate-to-severe white matter abnormalities were characterized by performance impairments across all measures and time points, with more severe cerebral abnormalities being associated with increased risks of cognitive impairment. These associations persisted after adjustment for gender, neonatal medical risk factors, and family social risk. Conclusions: Findings highlight the importance of cerebral white matter connectivity for later intact cognitive functioning amongst children born very preterm. Preterm born children without cerebral white matter abnormalities on their term MRI appear to be spared many of the cognitive impairments commonly associated with preterm birth. Further follow-up will be important to assess whether this finding persists into the school years. © 2012 Woodward et al.

Document Type: Article
Source: Scopus

 

Shin, J.E.a , Miller, B.R.a e f , Babetto, E.a , Cho, Y.b , Sasaki, Y.c , Qayum, S.a , Russler, E.V.a, Cavalli, V.b d , Milbrandt, J.c d , DiAntonio, A.a d 
SCG10 is a JNK target in the axonal degeneration pathway
(2012) Proceedings of the National Academy of Sciences of the United States of America, 109 (52), pp. E3696-E3705. 

a Department of Developmental Biology, Washington University School of Medicine, St. Louis, MO 63110, United States
b Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, MO 63110, United States
c Department of Genetics, Washington University School of Medicine, St. Louis, MO 63110, United States
d Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO 63110, United States
e Department of Psychiatry, Columbia University, New York, NY 10032, United States
f New York State Psychiatric Institute, New York, NY 10032, United States

Abstract
Axons actively self-destruct following genetic, mechanical, metabolic, and toxic insults, but the mechanism of axonal degeneration is poorly understood. The JNK pathway promotes axonal degeneration shortly after axonal injury, hours before irreversible axon fragmentation ensues. Inhibition of JNK activity during this period delays axonal degeneration, but critical JNK substrates that facilitate axon degeneration are unknown. Here we show that superior cervical ganglion 10 (SCG10), an axonal JNK substrate, is lost rapidly from mouse dorsal root ganglion axons following axotomy. SCG10 loss precedes axon fragmentation and occurs selectively in the axon segments distal to transection that are destined to degenerate. Rapid SCG10 loss after injury requires JNK activity. The JNK phosphorylation sites on SCG10 are required for its rapid degradation, suggesting that direct JNK phosphorylation targets SCG10 for degradation. We present a mechanism for the selective loss of SCG10 distal to the injury site. In healthy axons, SCG10 undergoes rapid JNK-dependent degradation and is replenished by fast axonal transport. Injury blocks axonal transport and the delivery of SCG10, leading to the selective loss of the labile SCG10 distal to the injury site. SCG10 loss is functionally important: Knocking down SCG10 accelerates axon fragmentation, whereas experimentally maintaining SCG10 after injury promotes mitochondrial movement and delays axonal degeneration. Taken together, these data support the model that SCG10 is an axonal-maintenance factor whose loss is permissive for execution of the injury-induced axonal degeneration program.

Document Type: Article
Source: Scopus

 

Nicolas, S.a , Levine, Z.b 
Beyond intelligence testing: Remembering alfred binet after a century
(2012) European Psychologist, 17 (4), pp. 320-325. 

a Paris Descartes University, Boulogne-Billancourt, France
b Washington University, St. Louis, MO, United States

Abstract
Though Alfred Binet was a prolific writer, many of his 1893-1903 works are not well known. This is partly due to a lack of English translations of the many important papers and books that he and his collaborators created during this period. Binet's insights into intelligence testing are widely celebrated, but the centennial of his death provides an occasion to reexamine his other psychological examinations. His studies included many diverse aspects of mental life, including memory research and the science of testimony. Indeed, Binet was a pioneer of psychology and produced important research on cognitive and experimental psychology, developmental psychology, social psychology, and applied psychology. This paper seeks to elucidate these aspects of his work. © 2011 Hogrefe Publishing.

Author Keywords
Binet;  History of psychology;  Intelligence;  Memory;  Testimony

Document Type: Review
Source: Scopus

 

Helwani, M.A.a , Saied, N.N.b 
Intraoperative plateau pressure measurement using modern anesthesia machine ventilators
(2012) Canadian Journal of Anesthesia, pp. 1-3. Article in Press. 

a Washington University School of Medicine, St. Louis, United States
b Vanderbilt University School of Medicine, TN, United States

Document Type: Article in Press
Source: Scopus

 

Ushe, M.a , Perlmutter, J.S.a b c d e 
Oromandibular and lingual dystonia associated with spinocerebellar ataxia type 8
(2012) Movement Disorders, 27 (14), pp. 1741-1743. 

a Department of Neurology, Washington University, School of Medicine, St. Louis, MO, United States
b Department of Radiology, Washington University, School of Medicine, St. Louis, MO, United States
c Department of Anatomy and Neurobiology, Washington University, School of Medicine, St. Louis, MO, United States
d Program in Physical Therapy, Washington University, School of Medicine, St. Louis, MO, United States
e Program in Occupational Therapy, Washington University, School of Medicine, St. Louis, MO, United States

Document Type: Note
Source: Scopus

 

Hacker, C.D.a , Perlmutter, J.S.b , Criswell, S.R.c , Ances, B.M.c , Snyder, A.Z.b 
Resting state functional connectivity of the striatum in Parkinson's disease
(2012) Brain, 135 (12), pp. 3699-3711. 

a Department of Biomedical Engineering, Washington University School of Medicine, Saint Louis, MO 63110, United States
b Department of Radiology, Washington University School of Medicine, Campus Box 8225, 4535 Scott Avenue, Saint Louis, MO 63110, United States
c Department of Neurology, Washington University School of Medicine, Saint Louis, MO 63110, United States

Abstract
Classical accounts of the pathophysiology of Parkinson's disease have emphasized degeneration of dopaminergic nigrostriatal neurons with consequent dysfunction of cortico-striatal-thalamic loops. In contrast, post-mortem studies indicate that pathological changes in Parkinson's disease (Lewy neurites and Lewy bodies) first appear primarily in the lower brainstem with subsequent progression to more rostral parts of the neuraxis. The nigrostriatal and histological perspectives are not incompatible, but they do emphasize different anatomical structures. To address the question of which brain structures are functionally most affected by Parkinson's disease, we performed a resting-state functional magnetic resonance imaging study focused on striatal functional connectivity. We contrasted 13 patients with advanced Parkinson's disease versus 19 age-matched control subjects, using methodology incorporating scrupulous attention to minimizing the effects of head motion during scanning. The principal finding in the Parkinson's disease group was markedly lower striatal correlations with thalamus, midbrain, pons and cerebellum. This result reinforces the importance of the brainstem in the pathophysiology of Parkinson's disease. Focally altered functional connectivity also was observed in sensori-motor and visual areas of the cerebral cortex, as well the supramarginal gyrus. Striatal functional connectivity with the brainstem was graded (posterior putamen > anterior putamen > caudate), in both patients with Parkinson's disease and control subjects, in a manner that corresponds to well-documented gradient of striatal dopaminergic function loss in Parkinson's disease. We hypothesize that this gradient provides a clue to the pathogenesis of Parkinson's disease. © 2012 The Author.

Author Keywords
brainstem;  functional MRI;  functional reorganization;  Parkinson's disease;  striatum

Document Type: Article
Source: Scopus