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WUSTL Neuroscience Publications Archive - August 2012

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August 29, 2012

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August 29, 2012

 

Duncan, A.E.a b , Lessov-Schlaggar, C.N.c , Sartor, C.E.b c d , Bucholz, K.K.b c
Differences in time to onset of smoking and nicotine dependence by race/ethnicity in a Midwestern sample of adolescents and young adults from a high risk family study
(2012) Drug and Alcohol Dependence, 125 (1-2), pp. 140-145. 

a The Brown School, Washington University, St. Louis, MO 63130, United States
b Midwest Alcoholism Research Center, Department of Psychiatry, Washington University School of Medicine, St. Louis, MO 63110, United States
c Department of Psychiatry, Washington University School of Medicine, St. Louis, MO 63130, United States
d Department of Psychiatry, Yale University School of Medicine, West Haven, CT 06516, United States

Abstract
Objective: The objective of this study was to determine whether race/ethnicity was associated with time to smoking initiation and time from first cigarette to onset of DSM-IV nicotine dependence (ND) after adjusting for familial and individual psychosocial risk factors. Methods: Cox proportional hazards models with time-dependent covariates were used to analyze data from 1376 offspring aged 12-33 years from 532 families at high risk for substance use problems due to paternal alcohol problems and 235 low risk families. Fifty-six percent of the sample self-identified as African-American (AA) and 44% were mainly of European descent. Results: Controlling for covariates, AAs began smoking at older ages (HR = 0.58; 95% CI: 0.48-0.70) and had longer times between smoking initiation and onset of ND compared to non-AAs (HR = 0.25, 95% CI: 0.16-0.39 for ND onset occurring <18 years and HR = 0.49, 95% CI: 0.30-0.80 for ND onsets ≥age 18). After additionally controlling for number of cigarettes smoked daily, the racial/ethnic effects for onset of ND were attenuated, but remained statistically significant for ND onset <18 (HR = 0.34, 95% CI: 0.19-0.61); however, the estimate was no longer significant for later ND onset (HR = 0.84, 95% CI: 0.50-1.41). Conclusions: AA adolescents and young adults initiate smoking at older ages and have longer transition periods between initiation and onset of ND compared to non-AAs, even after controlling for many relevant psychiatric and psychosocial covariates; however, racial/ethnic differences in time to onset of nicotine dependence in late adolescence and young adulthood may be explained by differences in daily quantity smoked. © 2012 Elsevier Ireland Ltd.


Author Keywords
Nicotine dependence;  Racial/ethnic differences;  Smoking initiation


Document Type: Article
Source: Scopus

 

Berg, C.a , Edwards, D.F.b , King, A.c
Executive function performance on the children's kitchen task assessment with children with sickle cell disease and matched controls
(2012) Child Neuropsychology, 18 (5), pp. 432-448. 


a Department of Occupational Therapy and Neurology, Washington University School of Medicine, Program in Occupational Therapy, 4444 Forest Park Ave., St. Louis, MO 63108, United States
b Department of Kinesiology-Occupational Therapy Program, Neurology and Medicine, University of Wisconsin, Madison, WI, United States
c Department of Occupational Therapy and Pediatrics, Washington University School of Medicine, St. Louis, MO, United States

Abstract
Objective: The aim of this study was to compare executive function abilities of 8-to 12-year-old children with sickle cell disease (SCD) with a matched control sample. The measures included the parent and teacher Behavior Rating Inventory of Executive Function (BRIEF); the Delis-Kaplan Executive Function System (D-KEFS), Free Sorting Test and Color Word Interference Test; and the Children's Kitchen Task Assessment (CKTA), a new performance measure. Methods: Twenty-two children with SCD were recruited from one hematology clinic and 22 community children, matched on characteristics of age, gender, and race, were selected from a larger sample of controls for comparison. Parents and teachers completed rating scales. Results:As hypothesized, children with SCD scored significantly lower than matched controls on Digit Span Forward; on 5 of the 9 D-KFES Color Word Interference and Sorting tasks; on CKTA organization, initiation, and task completion; and on the BRIEF's parent and teacher Metacognitive Index (MI) and Global Executive Composite (GEC) scores. Conclusion:Cognitive and performance evaluations indicate lower executive function among children with SCD. Results substantiate the need for evaluative triangulation for children with SCD: Neurocognitive testing supported by performance testing, and adult reflection of a child's daily performance compared to other children. These elements will provide rich data to create educational support for children with SCD who have frequent hospitalizations, school absences, and the potential presence of cerebral vascular accident symptomology. © 2012 Psychology Press.


Author Keywords
Ecological validity;  Executive function;  Neurocognitive assessment;  Performance assessment;  Sickle cell disease


Document Type: Article
Source: Scopus

 

Milivojevic, D.a , Milovanovic, S.D.b c , Jovanovic, M.d , Svrakic, D.M.e , Svrakic, N.M.e , Svrakic, S.M.a , Cloninger, C.R.e
Temperament and character modify risk of drug addiction and influence choice of drugs
(2012) American Journal on Addictions, 21 (5), pp. 462-467. 

a Specialized Hospital for Chemical Dependence Naltrexzone, Beograd, Serbia
b Department of Psychiatry, University of Belgrade, Belgrade, Serbia
c Clinical Center of Serbia, Clinic for Psychiatry, Belgrade, Serbia
d CC Kragujevac Psychiatric Clinic, Kragujevac, Serbia
e Department of Psychiatry, Washington University School of Medicine, Campus Box 8134, 660 S Euclid Ave., St. Louis, MO 63110, United States

Abstract
Background: Drug addiction and alcoholism involve a complex etiopathogenesis with a variable degree of risk contributions from the host (person), environment, and addictive substances. In this work, temperament and character features of individuals addicted to opiates or alcohol are compared with normal controls to study personality factors in the overall risk for drug addiction. Methods: The study was done in a permissive environment, with easy access to alcohol and heroin, which facilitated analyses of personality factors in drug choice. Participants included 412 consecutive patients (312 opiate addicts, 100 alcohol addicts) treated at the Specialized Hospital for Chemical Dependency in Belgrade, Serbia, and a community sample of 346 controls. Results: Opiate addicts manifested antisocial temperament configuration (high Novelty Seeking, low Reward Dependence) coupled with high Self-transcendence (ie, susceptibility to fantasy and imagination). Alcohol addicts manifested sensitive temperament configuration (high Novelty Seeking coexisting with high Harm Avoidance). Immature personality was observed far more frequently in opiate addicts than in alcoholics or normals. Conclusions: Novelty Seeking appears to be a general risk factor for drug addiction. High Harm Avoidance appears to channel individuals with high Novelty Seeking towards alcoholism. Immature character traits and probable Personality Disorder increase the risk of illegal drugs. Based on equivalent research in nonpermissive environments, at least a portion of our opiate addicts could have developed alcoholism instead in environments with more limited access to opiates. Personality factors provide useful guidelines for preventive work with young individuals with personality risk factors for drug addiction. Copyright © American Academy of Addiction Psychiatry.


Document Type: Article
Source: Scopus

 

Schrepf, A.a , Clevenger, L.a , Christensen, D.a , DeGeest, K.b , Bender, D.b , Ahmed, A.b , Goodheart, M.J.b c , Dahmoush, L.d , Penedo, F.e , Lucci III, J.A.f , Ganjei-Azar, P.g , Mendez, L.h , Markon, K.a , Lubaroff, D.M.c i j , Thaker, P.H.k , Slavich, G.M.l , Sood, A.K.m , Lutgendorf, S.K.a b c i
Cortisol and inflammatory processes in ovarian cancer patients following primary treatment: Relationships with depression, fatigue, and disability
(2012) Brain, Behavior, and Immunity, . Article in Press. 

a Department of Psychology, University of Iowa, USA
b Department of Obstetrics and Gynecology, University of Iowa, USA
c Holden Comprehensive Cancer Center, University of Iowa, USA
d Department of Pathology, University of Iowa, USA
e Department of Psychology and Sylvester Comprehensive Cancer Center, University of Miami, USA
f Division of Gynecologic Oncology and Sylvester Comprehensive Cancer Center, University of Miami, USA
g Department of Pathology and Sylvester Comprehensive Cancer Center, University of Miami, USA
h Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Florida International University School of Medicine, USA
i Department of Urology, University of Iowa, USA
j Department of Microbiology, University of Iowa, USA
k Washington University School of Medicine, USA
l Cousins Center for Psychoneuroimmunology and Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, USA
m Departments of Gynecologic Oncology and Cancer Biology, UT MD Anderson Comprehensive Cancer Center, USA

Abstract
Elevations in the pro-inflammatory cytokine interleukin-6 (IL-6) and alterations in the anti-inflammatory hormone cortisol have been reported in a variety of cancers. IL-6 has prognostic significance in ovarian cancer and cortisol has been associated with fatigue, disability, and vegetative depression in ovarian cancer patients prior to surgery. Ovarian cancer patients undergoing primary treatment completed psychological self-report measures and collected salivary cortisol and plasma IL-6 prior to surgery, at 6 months, and at 1 year. Patients included in this study had completed chemotherapy and had no evidence of disease recurrence. At 6 months, patients showed significant reductions in nocturnal cortisol secretion, plasma IL-6, and a more normalized diurnal cortisol rhythm, changes that were maintained at 1 year. The reductions in IL-6 and nocturnal cortisol were associated with declines in self-reported fatigue, vegetative depression, and disability. These findings suggest that primary treatment for ovarian cancer reduces the inflammatory response. Moreover, patients who have not developed recurrent disease by 1 year appear to maintain more normalized levels of cortisol and IL-6. Improvement in fatigue and vegetative depression is associated with the normalization of IL-6 and cortisol, a pattern which may be relevant for improvements in overall quality of life for ovarian cancer patients. © 2012.


Author Keywords
Cortisol;  Depression;  Disability;  Fatigue;  IL-6;  Inflammation;  Ovarian cancer


Document Type: Article in Press
Source: Scopus

 

McCutcheon, V.V.a , Scherrer, J.F.a b , Grant, J.D.a , Xian, H.b d , Haber, J.R.c , Jacob, T.c , Bucholz, K.K.a
Parent, sibling and peer associations with subtypes of psychiatric and substance use disorder comorbidity in offspring
(2012) Drug and Alcohol Dependence, . Article in Press. 

a Midwest Alcoholism Research Center, Department of Psychiatry, Washington University School of Medicine, 660 S. Euclid Avenue, Campus Box 8134, St. Louis, MO 63110, United States
b Research Service, St. Louis Veterans Affairs Medical Center, Research Service (151-JC), 915 North Grand Blvd, St. Louis, MO 63106, United States
c Palo Alto Department of Veterans Affairs Medical Center, MC 151J, 795 Willow Road, Palo Alto, CA 94025, United States
d Department of Biostatistics, Saint Louis University School of Public Health, 3545 Lafayette Avenue, St. Louis, MO 63104, United States

Abstract
Background: Parental substance use disorder (SUD) is associated with a range of negative offspring outcomes and psychopathology, but the clustering of these outcomes into subtypes has seldom been examined, nor have the familial and environmental contexts of these subtypes been reported. The present study examines the clustering of offspring lifetime substance use and psychiatric disorders into subtypes and characterizes them in terms of familial and non-familial influences using an offspring-of-twins design. Method: Telephone-administered diagnostic interviews were used to collect data on psychiatric disorders and SUD from 488 twin fathers, 420 biological mothers and 831 offspring. Latent class analysis (LCA) was used to derive subtypes of lifetime comorbidity in offspring. Familial risk and environmental variables associated with each subtype (i.e., parenting, childhood physical or sexual abuse, perceived sibling and peer substance use) were identified using multinomial logistic regression. Results: Four classes identified by LCA were characterized as (1) unaffected, (2) alcohol abuse/dependence, (3) alcohol abuse/dependence comorbid with anxiety and depression, and (4) alcohol, cannabis abuse/dependence and nicotine dependence comorbid with conduct disorder. Inconsistent parenting, childhood physical/sexual abuse, and perceived sibling and peer substance use were significantly associated with profiles of offspring comorbidity after adjusting for familial vulnerability. Some associations were specific (i.e., perceived peer alcohol use to the AUD class), while others were general (peer smoking to all 3 comorbidity classes). Conclusions: We observed distinct subtypes of psychiatric and SUD comorbidity in adolescents and young adults. Subtypes of offspring psychopathology have varied associations with parental psychopathology, family environment, and sibling and peer behaviors. © 2012 Elsevier Ireland Ltd.


Author Keywords
Anxiety;  Comorbid;  Depression;  Substance use disorder;  Twin


Document Type: Article in Press
Source: Scopus

 

Thoroughman, K.A., Khan, R.P., Sun, H., Widder, P.L.
Integration of a computational lab sequence into a junior-level quantitative physiology course
(2012) ASEE Annual Conference and Exposition, Conference Proceedings, 10 p. 


Department of Biomedical Engineering, Washington University, St. Louis, United States

Abstract
We have built a computational laboratory sequence within a junior-level quantitative physiology course within a biomedical engineering major. The course integrates mathematical, engineering, and biological perspectives into foundations of bioinstrumentation, models of physiology, and interfaces with physiological systems. We designed the computational labs to foster deeper and more facile understanding of core concepts as illustrated through dynamic system modeling. Here we assessed how students built this flexible facility, through assays of lab performance, practicum examination, and post-course survey. We conclude that the computational labs generated a framework for integrative and innovative understanding of course material. © 2012 American Society for Engineering Education.


Document Type: Conference Paper
Source: Scopus

 

Sartor, C.E.a , Mccutcheon, V.V.b , Nelson, E.C.b , Duncan, A.E.c , Bucholz, K.K.b , Heath, A.C.b
Investigating the association between childhood sexual abuse and alcohol use disorders in women: Does It matter how we ask about sexual abuse?
(2012) Journal of Studies on Alcohol and Drugs, 73 (5), pp. 740-748. 

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 George Warren Brown School of Social Work, Washington University, St. Louis, MO, United States

Abstract
The purpose of this study was to determine whether the type of questions used to assess childhood sexual abuse (CSA) introduces systematic bias into estimations of the magnitude of the association between CSA and alcohol use disorders (AUDs). Method: The Semi-Structured Assessment for the Genetics of Alcoholism was administered by telephone to 3,787 female twins ages 18-29 years (14.6% African American, 85.4% White). Interviews included questions regarding sexual abuse experiences described in behavioral terms and a standard trauma checklist (in a separate section) with the items "rape" and "sexual molestation," with defi nitions provided in respondent booklets. Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, diagnoses of alcohol abuse and dependence, parental history of alcohol-related problems, and psychiatric conditions associated with AUDs were also assessed. Results: The majority of women who endorsed one question type also endorsed the other type. Rates of psychiatric risk factors for AUDs did not vary by pattern of CSA question endorsement. Separate Cox proportional hazards regression analyses using CSA variables derived from behavioral questions (hazard ratio [HR] = 1.67, 95% CI [1.27, 2.19]) and checklist items (HR = 1.41, 95% CI [1.08, 1.84]) each revealed elevated risk for AUDs associated with CSA, and HRs did not differ significantly across models. However, a Cox proportional hazards regression analysis predicting AUD from the pattern of CSA question endorsements revealed a significantly higher risk for AUDs among women who endorsed only behavioral questions (HR = 3.26, 95% CI [1.72, 6.21]) than for all other groups. Conclusions: Findings underscore the importance of querying CSA in studies of alcohol-related problems and highlight some of the limitations of assessment methods that can be integrated into studies covering a wide range of psychosocial domains.


Document Type: Article
Source: Scopus

 

Aldridge, K.a , Wang, L.b , Harms, M.P.c , Moffitt, A.J.a , Cole, K.K.a , Csernansky, J.G.b , Selemon, L.D.d
A longitudinal analysis of regional brain volumes in macaques exposed to x-irradiation in early gestation
(2012) PLoS ONE, 7 (8), art. no. e43109, . 

a Department of Pathology and Anatomical Sciences, University of Missouri School of Medicine, Columbia, MO, United States
b Departments of Psychiatry and Behavioral Sciences and Radiology, Northwestern University Feinberg School of Medicine, Chicago, IL, United States
c Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, United States
d Department of Neurobiology, Yale University School of Medicine, New Haven, CT, United States

Abstract
Background: Early gestation represents a period of vulnerability to environmental insult that has been associated with adult psychiatric disease. However, little is known about how prenatal perturbation translates into adult brain dysfunction. Here, we use a longitudinal study design to examine the effects of disruption of early gestational neurogenesis on brain volume in the non-human primate. Methods and Principal Findings: Five Rhesus macaques were exposed to x-irradiation in early gestation (E30-E41), and four control monkeys were sham-irradiated at comparable ages. Whole brain magnetic resonance imaging was performed at 6 months, 12 months, and 3 and 5 years of age. Volumes of whole cerebrum, cortical gray matter, caudate, putamen, and thalamus were estimated using semi-automated segmentation methods and high dimensional brain mapping. Volume reductions spanning all ages were observed in irradiated monkeys in the putamen (15-24%, p = 0.01) and in cortical gray matter (6-15%, p = 0.01). Upon covarying for whole cerebral volume, group differences were reduced to trend levels (putamen: p = 0.07; cortical gray matter: p = 0.08). No group-by-age effects were significant. Conclusions: Due to the small number of observations, the conclusions drawn from this study must be viewed as tentative. Early gestational irradiation may result in non-uniform reduction of gray matter, mainly affecting the putamen and cerebral cortex. This may be relevant to understanding how early prenatal environmental insult could lead to brain morphological differences in neurodevelopmental diseases. © 2012 Aldridge et al.


Document Type: Article
Source: Scopus

 

Wissman, K.T.a , Rawson, K.A.a , Pyc, M.A.b
How and when do students use flashcards?
(2012) Memory, 20 (6), pp. 568-579. 


a Department of Psychology, Kent State University, P.O. Box 5190, Kent, OH 44242-0001, United States
b Department of Psychology, Washington University in St. Louis, St. Louis, MO, United States

Abstract
Previous survey research has documented students' use of self-regulated study strategies, with a particular interest in self-testing. These surveys indicate that students frequently use flashcards to self-test and that self-testing is primarily used as a way to monitor learning. Whereas previous surveys provide information about whether and why students self-test, they provide minimal information about how and when students choose to self-test. Accordingly, the primary purpose of the current survey was to explore how and when students engage in self-testing. We surveyed 374 undergraduates about the amount of practice and the timing of practice, two factors that strongly affect the efficacy of self-testing. Results indicate that students understand the benefits of practising to higher criterion levels (amount of practice) but do not typically implement or understand the benefits of practising with longer lags (timing of practice). We discuss practical implications for supporting more successful student learning. © 2012 Copyright Psychology Press Ltd.


Author Keywords
Criterion learning;  Lag effects;  Self-testing;  Survey


Document Type: Article
Source: Scopus

 

Huff, M.a , Papenmeier, F.a , Zacks, J.M.b
Visual target detection is impaired at event boundaries
(2012) Visual Cognition, 20 (7), pp. 848-864. 

a Department of Psychology, University of Tübingen, Schleichstr. 4, D-72076 Tübingen, Germany
b Department of Psychology, Washington University in St. Louis, St. Louis, MO, United States

Abstract
Boundaries between meaningful events are key moments in comprehending human action. At these points, viewers may focus on the event's contents at the expense of other information. We tested whether visual detection was impaired at those moments perceivers judged to be boundaries between events. Short animated football clips were used as stimulus material, and event boundaries were imposed by having the ball change possession. In a first experiment, we found that possession changes were perceived to be event boundaries. In a second experiment, participants were asked to keep track of 4 of 10 players and to watch for 120 ms probes appearing either at an event boundary or a nonboundary. Probe detection was less accurate at event boundaries. This result suggests that the segmentation of ongoing activity into events corresponds with the regulation of attention over time. © 2012 Copyright Psychology Press Ltd.


Author Keywords
Dynamic attention;  Event cognition;  Multiple object tracking;  Probe detection


Document Type: Article
Source: Scopus

 

Hilton, C.L., Zhang, Y., Whilte, M.R., Klohr, C.L., Constantino, J.
Motor impairment in sibling pairs concordant and discordant for autism spectrum disorders
(2012) Autism, 16 (4), pp. 430-441. 


Washington University in St Louis, 4444 Forest Park Ave, St Louis, MO 63108, United States

Abstract
Aim: Although motor impairment is frequently observed in children with autism spectrum disorders (ASD), the manner in which these impairments aggregate in families affected by autism is unknown. We used a standardized measure of motor proficiency to objectively examine quantitative variation in motor proficiency in sibling pairs concordant and discordant for ASD. Methods: Motor impairment of sibling pairs from 67 ASD-affected families comprising 29 concordant pairings and 48 discordant pairings were assessed using the Bruininks Oseretsky Test of Motor Proficiency, 2nd Edition, a standardized measure of motor proficiency. Results: Motor skills were substantially impaired among ASD-affected children and highly correlated with autistic severity and IQ, whereas motor skills in unaffected siblings were essentially normal. Total motor composite scores of at least one standard deviation below the general population mean were seen in 83% of the affected group compared with 6% in the unaffected siblings. Interpretation: Findings indicate that motor impairment constitutes a core characteristic of ASD (not necessarily an ASD endophenotype), which has distinct implications for taxonomy, diagnosis, and approaches to intervention. © 2012 The Author(s).


Author Keywords
agility;  body coordination;  endophenotype;  fine manual control;  manual dexterity;  motor coordination;  pervasive developmental disorder;  sibling studies;  strength


Document Type: Article
Source: Scopus

August 22, 2012

Johnson, K.J.
Pediatric brain tumors: Gene X environment interactions providing new clues?
(2012) Pediatric Blood and Cancer, 59 (4), pp. 597-598. 


Washington University in St. Louis, One Brookings Drive, St. Louis, MO, United States

Document Type: Note
Source: Scopus

 

Luciano, M.a b , Huffman, J.E.c , Arias-Vásquez, A.d , Vinkhuyzen, A.A.e , Middeldorp, C.M.f g , Giegling, I.h , Payton, A.i , Davies, G.b , Zgaga, L.j k , Janzing, J.l , Ke, X.m , Galesloot, T.n , Hartmann, A.M.h , Ollier, W.i , Tenesa, A.a o , Hayward, C.c , Verhagen, M.p , Montgomery, G.W.e , Hottenga, J.-J.f , Konte, B.h , Starr, J.M.a q , Vitart, V.c , Vos, P.E.r , Madden, P.A.s , Willemsen, G.f , Konnerth, H.h , Horan, M.A.t , Porteous, D.J.u , Campbell, H.k , Vermeulen, S.H.n , Heath, A.C.s , Wright, A.c , Polasek, O.v , Kovacevic, S.B.w , Hastie, N.D.c , Franke, B.d , Boomsma, D.I.f , Martin, N.G.e , Rujescu, D.h , Wilson, J.F.k , Buitelaar, J.x , Pendleton, N.y , Rudan, I.c v z , Deary, I.J.a b
Genome-wide association uncovers shared genetic effects among personality traits and mood states
(2012) American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics, 159 B (6), pp. 684-695. 


a Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, United Kingdom
b Department of Psychology, University of Edinburgh, Edinburgh, United Kingdom
c MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh, United Kingdom
d Departments of Psychiatry and Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands
e Queensland Institute of Medical Research, Brisbane, Australia
f Department of Biological Psychology, VU University Amsterdam, Amsterdam, Netherlands
g Department of Child and Adolescent Psychiatry, Amsterdam Medical Center and GGZ in Geest, VU University Medical Center, Amsterdam, Netherlands
h Department of Psychiatry, University of Munich (LMU), Munich, Germany
i CIGMR, School of Cancer and Enabling Sciences, University of Manchester, Greater Manchester, United Kingdom
j Department of Medical statistics, Epidemiology and Medical Informatics, Andrija Štampar School of Public Health, Zagreb University School of Medicine, Zagreb, Croatia
k Centre for Population Health Sciences, University of Edinburgh, Teviot Place, Edinburgh, United Kingdom
l Department of Psychiatry, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands
m Paediatric Epidemiology Unit, School of Life and Medical Sciences, Institute for Child Health, UCL, London, United Kingdom
n Departments of Epidemiology, Biostatistics and HTA and Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands
o The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Edinburgh, United Kingdom
p Behavioural Science Institute, Radboud University Nijmegen, Nijmegen, Netherlands
q Geriatric Medicine Unit, University of Edinburgh, Royal Victoria Hospital, Edinburgh, United Kingdom
r Department of Neurology, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands
s Washington University School of Medicine, St. Louis, Missouri, United States
t Clinical Neurosciences, School of Translational Medicine, The University of Manchester, Hope Hospital, Salford, Greater Manchester, United Kingdom
u University of Edinburgh Molecular Medicine Centre, Western General Hospital, Edinburgh, United Kingdom
v Department of Public Health, Medical School, University of Split, Split, Croatia
w University Hospital for Infectious Diseases, Zagreb, Croatia
x Donders Institute for Brain, Cognition and Behaviour, Department of Cognitive Neuroscience, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands
y Mental Health and Neurodegeneration Research Group, School of Community Based Medicine, The University of Manchester, Hope Hospital, Greater Manchester, United Kingdom
z Sisters of Mercy University Hospital, Zagreb, Croatia

Abstract
Measures of personality and psychological distress are correlated and exhibit genetic covariance. We conducted univariate genome-wide SNP (
2.5 million) and gene-based association analyses of these traits and examined the overlap in results across traits, including a prediction analysis of mood states using genetic polygenic scores for personality. Measures of neuroticism, extraversion, and symptoms of anxiety, depression, and general psychological distress were collected in eight European cohorts (n ranged 546-1,338; maximum total n=6,268) whose mean age ranged from 55 to 79 years. Meta-analysis of the cohort results was performed, with follow-up associations of the top SNPs and genes investigated in independent cohorts (n=527-6,032). Suggestive association (P=8×10 -8) of rs1079196 in the FHIT gene was observed with symptoms of anxiety. Other notable associations (P&lt;6.09×10 -6) included SNPs in five genes for neuroticism (LCE3C, POLR3A, LMAN1L, ULK3, SCAMP2), KIAA0802 for extraversion, and NOS1 for general psychological distress. An association between symptoms of depression and rs7582472 (near to MGAT5 and NCKAP5) was replicated in two independent samples, but other replication findings were less consistent. Gene-based tests identified a significant locus on chromosome 15 (spanning five genes) associated with neuroticism which replicated (P&lt;0.05) in an independent cohort. Support for common genetic effects among personality and mood (particularly neuroticism and depressive symptoms) was found in terms of SNP association overlap and polygenic score prediction. The variance explained by individual SNPs was very small (up to 1%) confirming that there are no moderate/large effects of common SNPs on personality and related traits. © 2012 Wiley Periodicals, Inc. Copyright © 2012 Wiley Periodicals, Inc..

Author Keywords
Anxiety;  Depression;  Extraversion;  GWAS;  Neuroticism


Document Type: Article
Source: Scopus

 

Lehmann, G.C.a , Bell, T.R.c , Kirkham, F.J.d , Gavlak, J.C.d , Ferguson, T.F.c , Strunk, R.C.a , Austin, P.b , Rosen, C.L.g , Marshall, M.J.d , Wilkey, O.e , Rodeghier, M.J.h , Warner, J.O.f , DeBaun, M.R.i
Enuresis Associated with Sleep Disordered Breathing in Children with Sickle Cell Anemia
(2012) Journal of Urology, . Article in Press. 


a Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri
b Department of Surgery, Division of Urology, Washington University School of Medicine, St. Louis, Missouri
c Department of Epidemiology, Saint Louis University School of Public Health, St. Louis, Missouri
d University College London Institute of Child Health, London, United Kingdom
e North Middlesex University Hospital, London, United Kingdom
f Biomedical Centre, Imperial College and Imperial College Healthcare NHS Trust, London, United Kingdom
g Department of Pediatrics, Division of Pediatric Pulmonology, Case Western Reserve University, Cleveland, Ohio
h Chicago, Illinois
i Department of Pediatrics, Vanderbilt University School of Medicine and Monroe Carell Jr. Children's Hospital at Vanderbilt, Nashville, Tennessee

Abstract
Purpose: Enuresis and sleep disordered breathing are common among children with sickle cell anemia. We evaluated whether enuresis is associated with sleep disordered breathing in children with sickle cell anemia. Materials and Methods: Baseline data were used from a multicenter prospective cohort study of 221 unselected children with sickle cell anemia. A questionnaire was used to evaluate, by parental report during the previous month, the presence of enuresis and its severity. Overnight polysomnography was used to determine the presence of sleep disordered breathing by the number of obstructive apneas and/or hypopneas per hour of sleep. Logistic and ordinal regression models were used to evaluate the association of sleep disordered breathing and enuresis. Results: The mean age of participants was 10.1 years (median 10.0, range 4 to 19). Enuresis occurred in 38.9% of participants and was significantly associated with an obstructive apnea-hypopnea index of 2 or more per hour after adjusting for age and gender (OR 2.19; 95% CI 1.09, 4.40; p = 0.03). Enuresis severity was associated with obstructive apneas and hypopneas with 3% or more desaturation 2 or more times per hour with and without habitual snoring (OR 3.23; 95% CI 1.53, 6.81; p = 0.001 and OR 2.07; 95% CI 1.09, 3.92; p = 0.03, respectively). Conclusions: In this unselected group of children with sickle cell anemia, sleep disordered breathing was associated with enuresis. Results of this study support that children with sickle cell anemia who present with enuresis should be evaluated by a pulmonologist for sleep disordered breathing. © 2012 American Urological Association Education and Research, Inc.


Author Keywords
anemia;  enuresis;  sickle cell;  sleep


Document Type: Article in Press
Source: Scopus

 

Srinivasakumar, P.a , Limbrick, D.b , Munro, R.b , Mercer, D.b , Rao, R.a , Inder, T.a , Mathur, A.a
Posthemorrhagic Ventricular Dilatation-Impact on Early Neurodevelopmental Outcome
(2012) American Journal of Perinatology, . Article in Press. 

a Division of Newborn Medicine, Washington University in St. Louis, St. Louis, Missouri
b Department of Pediatric Neurosurgery, Washington University in St. Louis, St. Louis, Missouri

Abstract
Objective This study evaluates the impact of ventricular dilatation following severe (grades III or IV) intraventricular hemorrhage (IVH) in preterm neonates and the current practice of neurosurgical interventions in infants with posthemorrhagic ventricular dilatation (PHVD) and early neurodevelopmental outcome. Study Design Premature neonates born at ≤34 weeks' gestational ages with severe IVH were identified retrospectively over a 5-year period (2005 to 2009). Standard measures of ventricular dilatation on head ultrasound (HUS) were recorded. The treatment of PHVD, timing of surgery including the type of temporizing neurosurgical procedure (TNP)-either a ventricular reservoir or a subgaleal shunt-and the subsequent need for ventriculoperitoneal (VP) shunt were evaluated. Patients were retrospectively stratified to an "early" versus "late" intervention group based on HUS measures. Early intervention was defined as TNP performed when the ventricular index (VI) was >97th percentile but <97th percentile + 4 mm. Late intervention was defined as TNP performed when VI was ≥97th percentile + 4 mm. Neurodevelopmental outcomes were evaluated at 18 to 24 months. Infants followed up for neurodevelopmental testing were stratified as group A (progressive PHVD with TNP), group B (PHVD without TNP), and group C (severe IVH without PHVD). Results One hundred seventy-three preterm neonates with severe IVH were identified during the study period, of whom 139/173 (80%) developed PHVD. Of these, 54 (54/139, 39%) received TNP either early (4/54, 7%) or late (50/54, 93%). Of those who received TNP, 32/54 (59%) required subsequent VP shunt placement. Neurodevelopmental testing was available in 39/109 (36%) infants who survived to discharge. The mean ± standard deviation cognitive, motor, and language composite scores were 77 ± 14.8, 67 ± 15.2, 70 ± 13.8 for group A (n = 16/39), 90 ± 7.8, 84 ± 9.6, 82 ± 18.2 for group B (n = 12/39), and 95 ± 14.3, 86 ± 10.7, 94 ± 15.8 for group C (n = 11/39), respectively (p < 0.006 for group A versus group B and p < 0.004 for group A versus group C across all domains). Increasing ventricular dilatation was associated with adverse motor, cognitive, and language outcomes (p = 0.002) and neonates with progressive PHVD requiring a TNP were most adversely affected (p = 0.0006). There were no differences in any outcome measures between the two types of TNPs. Clinical and demographic characteristics of infants lost to follow-up were not significantly different than those available for follow-up. Conclusion Increasing ventricular size adversely affects neurodevelopmental outcome in infants with PHVD. © Thieme Medical Publishers.


Author Keywords
head ultrasound;  intraventricular hemorrhage;  posthemorrhagic ventricular dilatation;  subgaleal shunt;  temporizing neurosurgical procedure;  ventricular index;  ventricular reservoir


Document Type: Article in Press
Source: Scopus

 

Yaghi, S.a , Moore, P.b , Ray, B.a , Keyrouz, S.G.c
Predictors of tracheostomy in patients with spontaneous intracerebral hemorrhage
(2012) Clinical Neurology and Neurosurgery, . Article in Press. 

a Department of Neurology, University of Arkansas for Medical Sciences, Little Rock, AR, United States
b Department of Biostatistics, University of Arkansas for Medical Sciences, Little Rock, AR, United States
c Department of Neurology, Washington University School of Medicine, St. Louis, MO, United States

Abstract
Background: One third of patients with intracerebral hemorrhage (ICH) require mechanical ventilation; in most, tracheostomy may be necessary. Limited data exist about predictors of tracheostomy in ICH. The aim of our study is to identify predictors of tracheostomy in ICH. Methods: We reviewed medical records of patients seen in our institution between 2005 and 2009, using ICD-9 codes for ICH, for admission clinical and radiological parameters. A stepwise logistic regression model was used to identify tracheostomy predictors. Results: Ninety patients with ICH were included in the analysis, eleven of which required tracheostomy. Patients requiring a tracheostomy were more likely to have a large hematoma volume (≥30 mL) (63.4% vs. 29.1%, p = 0.037), intraventricular hemorrhage (81.8% vs. 27.8%, p < 0.0001), hydrocephalus (81.8% vs. 8.8%, p < 0.0001), admission GCS < 8 (81.8% vs. 5.1%, p < 0.0001), intubation ≥ 14 days (54.5% vs. 1.27%, p < 0.0001) and pneumonia (63.6% vs. 17.7%, p = 0.003). Stepwise logistic regression yielded admission GCS (OR = 80.55, p = 0.0003) and intubation days (OR = 87.49, p < 0.006) as most important predictors. Conclusion: We could potentially predict the need for tracheostomy early in the course of ICH based on the admission GCS score; duration of intubation is another predictor for tracheostomy. Early tracheostomy could decrease the time, and therefore risks of prolonged endotracheal intubation and length of hospital stay. © 2012 Elsevier B.V. All rights reserved.


Author Keywords
Endotracheal intubation;  GCS;  Hydrocephalus;  Intracerebral hemorrhage;  Intraventricular hemorrhage;  Tracheostomy


Document Type: Article in Press
Source: Scopus

 

Agarwal, P.K.a , Bain, P.M.b , Chamberlain, R.W.c
The Value of Applied Research: Retrieval Practice Improves Classroom Learning and Recommendations from a Teacher, a Principal, and a Scientist
(2012) Educational Psychology Review, pp. 1-12. Article in Press. 

a Department of Psychology, Washington University in St. Louis, St. Louis, 63130, United States
b Columbia Middle School, Columbia, 62236, United States
c College of Education, Roosevelt University, Chicago, 60605, United States

Abstract
Over the course of a 5-year applied research project with more than 1,400 middle school students, evidence from a number of studies revealed that retrieval practice in authentic classroom settings improves long-term learning (Agarwal et al.2009; McDaniel et al., Journal of Educational Psychology 103:399-414, 2011; McDaniel et al.2012; Roediger et al., Journal of Experimental Psychology: Applied 17:382-395, 2011a). Retrieval practice, or the use of quizzes and exams to engage and enhance retrieval processes, has been widely established as an effective strategy for facilitating learning in laboratory settings (e.g., Roediger et al.2011c). In this article, we review recent findings from applied research that demonstrate that retrieval practice enhances long-term classroom learning, delayed quizzes are particularly potent for retention, quizzes benefit students' transfer to novel quiz items, and quizzes with feedback improve students' learning and metacognitive awareness. In addition to generating evidence to support retrieval-based learning, these applied research studies also enhanced the professional development of the teachers, administrators, and scientists involved in the project. In this article, it is our hope that by sharing what we have learned from a variety of perspectives, applied scientific research in K-12 classrooms will continue to be explored and generated at local, state, and national levels, improving student learning and educational decision-making. © 2012 Springer Science+Business Media, LLC.


Author Keywords
Applied research;  Education;  Quizzing;  Retrieval practice;  Teaching;  Testing effect


Document Type: Article in Press
Source: Scopus

 

Yeh, C.-H.a , Chien, L.-C.b , Chiang, Y.-C.c , Huang, L.-C.d
Auricular point acupressure for chronic low back pain: A feasibility study for 1-week treatment
(2012) Evidence-based Complementary and Alternative Medicine, 2012, art. no. 383257, . 

a School of Nursing, University of Pittsburgh, 3500 Victoria Street, Pittsburgh, PA 15261, United States
b Department of Internal Medicine, Washington University in St. Louis, St. Louis, MO, United States
c Department of Nursing, Chang Gung Institute of Technology, Taiwan
d World Academy of Auricular Medicine, FL, United States

Abstract
Objectives. The objective of this one-group, repeated-measures design was to explore the acceptance of auricular point acupressure (APA) to reduce chronic low back pain (CLBP) and estimate minimum clinically important differences (MCIDs) for pain intensity change. Methods. Subjects received 7-day APA treatment. After appropriate acupoints were identified, vaccaria seeds were carefully taped onto each selected auricular point for 7-day. The Brief Pain Inventory Short Form (BPI) was used to collect outcome data. Results. A total of 74 subjects participated in the study. Ten subjects dropped out and the retention rate was 87. Subjects reported a 46 reduction in BPI worst pain, and over 50 reduction in BPI average pain, overall pain severity and pain interference by the end of study, and 62.5 subjects also reported less pain medication use. The MCIDs for the subscale of BPI ranged from.70 to 1.86 points. The percentage improvement of MCIDs from baseline was between 14.524.9. Discussion. APA appears to be highly acceptable to patients with CLBP. A sham group is needed in order to differentiate the true effects of APA from the possible psychological effects of more frequent visits by the auricular therapist and patients expectation of the APA treatment. © 2012 Chao-Hsing Yeh et al.


Document Type: Article
Source: Scopus

 

Chen, P.-L.a , Chen, W.-S.a , Li, J.a , Lind, A.C.a , Lu, D.b c
Diagnostic utility of neural stem and progenitor cell markers nestin and SOX2 in distinguishing nodal melanocytic nevi from metastatic melanomas
(2012) Modern Pathology, . Article in Press. 

a Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO, USA
b 1] Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO, USA
c Department of Pathology, St Luke's Hospital, Chesterfield, MO, USA

Abstract
Sentinel lymph node evaluation is a critical component of melanoma staging, and lymph node status provides one of the most powerful predictors of melanoma recurrence and survival. One of the well-known diagnostic pitfalls in melanoma sentinel lymph node evaluation is the presence of nodal melanocytic nevi, which has been demonstrated in up to 26% of lymphadenectomy specimens and specifically in melanoma patients. Melanocytic markers enhance the sensitivity of melanoma detection in sentinel lymph nodes. However, established markers such as anti-melan-A/MART1, S100 protein and SOX10 antibodies cannot discriminate melanoma metastasis from nodal nevi. Recent studies have demonstrated strong expression of neural stem/progenitor cell markers nestin and SOX2 in melanoma. In this study, we tested the diagnostic utility of nestin and SOX2 in differentiating metastatic melanomas from nodal nevi. Twenty-three lymph nodes with metastatic melanomas and 17 with nodal nevi were examined. Of the 23 metastatic melanomas, 18 showed diffuse and strong (3+) nestin, 4 showed rare cells with strong (3+) nestin, and one showed diffuse but faint (1+) nestin staining. Nuclear SOX2 was positive in 13 metastatic melanomas. In contrast, 15 nodal nevi showed no nestin, and 2 showed rare cells with very faint (<1+) nestin staining. SOX2 was negative in 13 nodal nevi. Overall, nestin was strongly expressed in metastatic melanomas (n=22/23; 96%), but not in nodal melanocytic nevi (n=15/17; 88%; P<0.0001). SOX2 was also expressed in metastatic melanomas (n=13/23; 57%) but not in the majority of nodal melanocytic nevi (n=13/16; 81%; P=0.02). In one lymph node harboring metastatic melan-A-negative desmoplastic melanoma, nestin and SOX2 strongly highlighted the infiltrating tumor cells, suggesting the potential clinical value of these two markers in desmoplastic melanoma lymph node biopsies. This study provides evidence that nestin and SOX2 can effectively differentiate nodal melanocytic nevi from metastatic melanomas and serve as powerful diagnostic adjuncts in melanoma staging.Modern Pathology advance online publication, 17 August 2012; doi:10.1038/modpathol.2012.132.


Document Type: Article in Press
Source: Scopus

 

Furlani, E.P.a b , Nunez, A.c d , Vizzeri, G.e
Modeling fluid structure-interactions for biomechanical analysis of the human eye
(2012) Technical Proceedings of the 2012 NSTI Nanotechnology Conference and Expo, NSTI-Nanotech 2012, pp. 337-340. 

a Dept. of Chemical and Biological Engineering, University at Buffalo SUNY, United States
b Dept. of Electrical Engineering, University at Buffalo SUNY, United States
c Department of Cardiothoracic Surgery, Washington University School of Medicine St Louis, United States
d Department of Cardiothoracic Surgery, St. Mary's Good Samaritan Regional Health Center Illinois, United States
e Department of Ophthalmology and Visual Sciences, University of Texas Medical Branch, United States

Abstract
A method is presented for studying and quantifying the biomechanical behavior of the human eye under elevated fluid and structural pressure loading. The approach taken involves a coupled synergistic computer modeling and experimental effort in which numerical models are used to predict the biomechanical response of eye under pressure, and physical cadaveric eye models along with appropriate imaging modalities are used to validate the theoretical predictions of tissue deformation within the eye. The numerical models are based on computational fluid dynamic (CFD) analysis combined wim a fully-coupled fluid-structure interaction (FSI) capability. Preliminary numerical modeling results of pressure-induced tissue deformation are demonstrated via application to an idealized eye geometry. A discussion is given of challenges and opportunities of using this approach to advance understanding of biomechanical behavior of the human eye.


Author Keywords
Astronaut ocular abnormalities;  Biomechanics of the eye;  Fluid structure interactions;  Intraocular pressure;  Optic nerve stress;  Stress and strain of eye tissue


Document Type: Conference Paper
Source: Scopus

August 15, 2012

Naylor, S.A., Diantonio, A.
EGFR signaling modulates synaptic connectivity via Gurken
(2012) Developmental Neurobiology, 72 (9), pp. 1229-1242. 


Department of Developmental Biology, Washington University School of Medicine, St. Louis, MO 63110, United States

Abstract
Synaptic target selection is critical for establishing functional neuronal circuits. The mechanisms regulating target selection remain incompletely understood. We describe a role for the EGF receptor and its ligand Gurken in target selection of octopaminergic Type II neurons in the Drosophila neuromuscular system. Mutants in happyhour, a regulator of EGFR signaling, form ectopic Type II neuromuscular junctions. These ectopic innervations are due to inappropriate target selection. We demonstrate that EGFR signaling is necessary and sufficient to inhibit synaptic target selection by these octopaminergic Type II neurons, and that the EGFR ligand Gurken is the postsynaptic, muscle-derived repulsive cue. These results identify a new pathway mediating cell-type and branch-specific synaptic repulsion, a novel role for EGFR signaling in synaptic target selection, and an unexpected role for Gurken as a muscle-secreted repulsive ligand. © 2011 Wiley Periodicals, Inc. Develop Neurobiol, 2012.

Author Keywords
EGFR;  Gurken;  Synaptic repulsion;  Target selection;  Type II neuron

Document Type: Article
Source: Scopus


Phua, P.D.a , Al-Samkari, H.T.b , Borschel, G.H.a c d
Is the term "obstetrical brachial plexus palsy" obsolete? An international survey to assess consensus among peripheral nerve surgeons
(2012) Journal of Plastic, Reconstructive and Aesthetic Surgery, 65 (9), pp. 1227-1232. 

a Division of Plastic and Reconstructive Surgery, Hospital for Sick Children, 555 University Ave, Toronto ON M5G 1X8, Canada
b Division of Plastic and Reconstructive Surgery, Washington University, St. Louis, MO, United States
c Department of Surgery, University of Toronto, Toronto, ON, Canada
d Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, ON, Canada

Abstract
Background: Brachial plexus injury diagnosed following delivery often causes lifelong disability and frequently results in litigation. While there is no universally accepted name for this condition, the term 'obstetrical brachial plexus palsy' (OBPP) is commonly used worldwide. The difficulty with the term 'OBPP' lies with the use of the word 'obstetrical', which some have construed to imply obstetrical malpractice even if none occurred. Many regions, especially in the United States, are suffering increasing obstetrician shortages, sometimes as a result of unsustainable liability insurance premiums. We wanted to determine whether surgeons felt that an alternative to the term 'OBPP' was more appropriate. Methods: We surveyed peripheral nerve surgeons worldwide to determine the appropriateness of the term 'OBPP' and alternative terms. Results: The majority of US-based surgeons (94%) preferred alternative terms, such as 'neonatal brachial plexus palsy'. However, only 53% of surgeons from other regions preferred alternative terms. This difference was statistically significant (p < 0.0002). Conclusions: More precise and descriptive alternatives to the term 'OBPP' are available and acceptable to many surgeons. An alternative to 'OBPP' may improve communication between practitioners, families and the legal system, especially in the United States. Our peripheral nerve organisations may be able to provide further leadership on this matter. © 2012 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

Author Keywords
Birth brachial plexus palsy;  Brachial plexus;  Erb's palsy;  Infant brachial plexus palsy;  International consensus;  Medico-legal;  Neonatal brachial plexus palsy;  Nerve injury;  Obstetrical brachial plexus palsy;  Peripheral nerve;  Survey

Document Type: Review
Source: Scopus

 
Lenze, E.J.a , Skidmore, E.R.b , Begley, A.E.c , Newcomer, J.W.e , Butters, M.A.c , Whyte, E.M.c d
Memantine for late-life depression and apathy after a disabling medical event: A 12-week, double-blind placebo-controlled pilot study
(2012) International Journal of Geriatric Psychiatry, 27 (9), pp. 974-980. 

a Department of Psychiatry, Washington University, St. Louis, MO, United States
b Department of Occupational Therapy, School of Health and Rehabilitation Sciences, University of Pittsburgh, Pittsburgh, PA, United States
c Department of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, PA, United States
d Department of Physical Medicine and Rehabilitation, School of Medicine, University of Pittsburgh, Pittsburgh, PA, United States
e Department of Psychiatry, University of Miami, Miami, FL, United States

Abstract
Objective Preclinical data suggests that memantine, a noncompetitive glutamate N-methyl- D-aspartate-receptor blocker used for the treatment of moderate to severe Alzheimer's disease, could reduce depressive and amotivated behavior occurring in the context of psychosocial stress. Therefore, we examined whether memantine could reduce depressive symptoms and amotivation manifesting in older adults after a disabling medical event, thereby improving their functional recovery. Method We recruited subjects aged 60 years and older who had recently suffered a disabling medical event and were admitted to a skilled nursing facility for rehabilitation. Participants with significant depressive symptoms, defined as a Hamilton Rating Scale for Depression score of 10 or greater, and/or significant apathy symptoms, defined as an Apathy Evaluation Scale score of 40 or greater, were randomized to memantine (10 mg/d for 1 week, then 10 mg twice daily) or placebo, for 12 weeks. We also recruited participants without depressive or apathy symptoms for naturalistic follow-up as a non-depressed comparison group. Depressive and apathy symptoms were main outcomes; functional recovery, and self-report rating of helplessness, and onset of new depressive disorders were secondary outcomes. Results Thirty-five older adults with significant depressive and/or apathy symptoms were randomized, of whom 27 (77.1%) completed the 12 week randomized controlled trial. Both groups showed reduction in depressive symptoms (but no significant reduction in apathy symptoms) and improved function. However, there were no group differences between the memantine-randomized and placebo randomized participants on any outcome. Conclusion Memantine was not associated with superior affective or functional outcome compared with placebo in medically rehabilitating older adults with depressive and apathy symptoms. Copyright © 2011 John Wiley & Sons, Ltd.

Author Keywords
depression;  disability;  memantine;  motivation;  older;  participation;  rehabilitation;  treatment

Document Type: Article
Source: Scopus

 
Zaidman, C.M.a , Holland, M.R.b , Hughes, M.S.c
Quantitative Ultrasound of Skeletal Muscle: Reliable Measurements of Calibrated Muscle Backscatter from Different Ultrasound Systems
(2012) Ultrasound in Medicine and Biology, 38 (9), pp. 1618-1625. 

a Department of Neurology, Neuromuscular Division, Washington University School of Medicine, St. Louis, MO, United States
b Department of Physics, Washington University, St. Louis, MO, United States
c Department of Medicine, Cardiovascular Division, Washington University School of Medicine, St. Louis, MO, United States

Abstract
Widespread implementation of quantitative muscle ultrasonography in assessing skeletal muscle pathology is limited by an inability to replicate results between different ultrasound systems. We have developed a measurement of skeletal muscle pathology, calibrated muscle backscatter (cMB), which should be reproducible between different ultrasound systems. We compared the reliability of grayscale and cMB measurements between different ultrasound systems, configurations and region-of-interest (ROI) sizes. cMB of skeletal muscle was reliably measured (intraclass correlation coefficient [ICC] ≤0.98) despite very dissimilar grayscale levels (ICC ≤0.54). cMB reliability was highest between systems using similar settings (ICC: 0.82-0.98) and was lowest when transducer type varied (ICC: 0.47-0.71). Reliability was better from ROIs spanning a narrow range of depths compared with larger ranges. cMB measurements are more reliable than grayscale between different ultrasound systems and configurations. Measuring cMB could improve widespread implementation of quantitative ultrasound in assessments of skeletal muscle pathology. © 2012 World Federation for Ultrasound in Medicine & Biology.

Author Keywords
Adults;  Backscatter;  Children;  Muscle;  Myopathy;  Quantitative;  Reliability;  Ultrasound

Document Type: Article
Source: Scopus

 
Agarwal, P.K.
Advances in Cognitive Psychology Relevant to Education: Introduction to the Special Issue
(2012) Educational Psychology Review, pp. 1-2. Article in Press. 

Department of Psychology, Washington University in St. Louis, St. Louis, 63130, United States

Document Type: Article in Press
Source: Scopus

 
Peterson, D.S.a , Pickett, K.A.a b , Earhart, G.M.a c
Effects of levodopa on vividness of motor imagery in Parkinson disease
(2012) Journal of Parkinson's Disease, 2 (2), pp. 127-133. 

a Program in Physical Therapy, Washington University in St. Louis, Campus Box 8502, 4444 Forest Park Blvd., St. Louis, MO 63108-2212, United States
b Department of Neurology - Movement Disorders Section, Washington University in St. Louis, St. Louis, MO, United States
c Department of Anatomy and Neurobiology, Washington University in St. Louis, St. Louis, MO, United States

Abstract
Introduction: Motor imagery during functional magnetic resonance imaging is commonly used to understand the neural underpinnings of complex movements. This approach has recently been applied to individuals with Parkinson disease (PD) to better understand how brain function may relate to movement dysfunction. However, the ability of individuals with PD to imagine movements when "Off" dopamine replacement medication is poorly understood. Therefore, the primary purpose of the current study is to test the ability of people with PD to imagine movements while "On" and "Off" anti-Parkinson medication. Methods: Vividness of imagery was assessed in 28 individuals with mild to moderate PD (Hoehn and Yahr stages 1-3) via the Kinesthetic Visual Imagery Questionnaire (KVIQ-20) both "On" and "Off" anti-Parkinson medication. Vividness of imagery of 32 age-matched older adults was also assessed. Results: No differences in vividness of imagery were observed between "Off" and "On" medication states (p = 0.15). Imagery was similar between controls and PD both "Off" (p = 0.25) and "On" (p = 0.46) anti-Parkinson medication. A significant correlation was observed between imagery and disease severity while "On" anti-Parkinson medication (r = -0.49; p = 0.008). Discussion and conclusions: Vividness of movement imagery was not different between "Off" and "On" anti-Parkinson medications or between PD and controls. These results suggest that people with PD are able to imagine similarly to older adults both when "On" and "Off" anti-Parkinson medication, and supports the use of motor imagery in the "Off" medication state. © 2012 - IOS Press and the authors. All rights reserved.

Author Keywords
KVIQ;  levodopa;  motor imagery;  Parkinson's disease

Document Type: Article
Source: Scopus

 

Datema, F.R.a , Ferrier, M.B.b , Vergouwe, Y.c , Moya, A.d , Molenaar, J.e , Piccirillo, J.F.f , Baatenburg de Jong, R.J.a
Update and external validation of a head and neck cancer prognostic model
(2012) Head and Neck, . Article in Press. 

a Department of ENT and Head and Neck Surgery, Erasmus Medical Centre, Rotterdam, The Netherlands
b Department of ENT and Head and Neck Surgery, Leiden University Medical Centre, Leiden, The Netherlands
c Department of Public Health, Erasmus Medical Centre, Rotterdam, The Netherlands
d WAZ Mediengruppe, Essen, Germany
e Department of Oncological Documentation, Leiden University Medical Centre, Leiden, The Netherlands
f Department of Otolaryngology, Washington University Medical School of Medicine, St. Louis, Missouri

Abstract
Background: The purpose of this study was to update and external validation of a prognostic model that is able to predict the survival probability of newly diagnosed patients with head and neck cancer. Methods: Our original prognostic model is based on historical data of 1371 patients with primary head and neck cancer, diagnosed and treated in the Leiden University Medical Center, between 1981 and 1999. The model contains the predictors age, sex, tumor site, TNM-classification, prior tumors, and comorbidity. We updated the model with follow-up data until January 2010. The updated model was then externally validated in 598 patients with head and neck cancer from the Siteman Cancer Center/Barnes-Jewish Hospital, St. Louis, Missouri. Results: Median follow-up was 5.5 years (range, 0-25.5). Only 2.5% of patients were lost to follow-up. During follow-up 1099 patients (80.2%) passed away. Discrimination of the updated prognostic model was good, with a C-index of 0.73 after internal validation. The discrimination was slightly lower in the external validation set (C-index, 0.69). The predicted 2-year and 5-year survival rates correlated satisfactorily with some slight deviations from the perfect calibration line. Conclusions: We used recent follow-up information to update the Leiden prognostic model for newly diagnosed patients with head and neck cancer. The model showed acceptably good calibration and discrimination results in internal and external validation procedures. © 2012 Wiley Periodicals, Inc.

Author Keywords
External validation;  Head and neck;  Internal validation;  Prognosis prediction;  Squamous cell carcinoma

Document Type: Article in Press
Source: Scopus

 

Halliday, G.a , Bigio, E.H.b , Cairns, N.J.c , Neumann, M.d , Mackenzie, I.R.A.e , Mann, D.M.A.f g
Mechanisms of disease in frontotemporal lobar degeneration: gain of function versus loss of function effects
(2012) Acta Neuropathologica, pp. 1-10. Article in Press. 

a Neuroscience Research Australia, University of New South Wales, Sydney, Australia
b Alzheimer Disease Center, Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, United States
c Department of Neurology, Washington University School of Medicine, St. Louis, United States
d Department of Neuropathology, German Center for Neurodegenerative Diseases Tuebingen, University of Tuebingen, Tuebingen, Germany
e Department of Pathology, University of British Columbia, Vancouver, Canada
f Institute of Brain, Behaviour and Mental Health, School of Community Based Medicine, University of Manchester, Manchester, United Kingdom
g Salford Royal Hospital, University of Manchester, Stott Lane, Salford, M6 8HD, United Kingdom

Abstract
Frontotemporal lobar degeneration (FTLD) is clinically, pathologically and genetically heterogeneous. Three major proteins are implicated in its pathogenesis. About half of cases are characterized by depositions of the microtubule associated protein, tau (FTLD-tau). In most of the remaining cases, deposits of the transactive response (TAR) DNA-binding protein with Mw of 43 kDa, known as TDP-43 (FTLD-TDP), are seen. Lastly, about 5-10 % of cases are characterized by abnormal accumulations of a third protein, fused in sarcoma (FTLD-FUS). Depending on the protein concerned, the signature accumulations can take the form of inclusion bodies (neuronal cytoplasmic inclusions and neuronal intranuclear inclusions) or dystrophic neurites, in the cerebral cortex, hippocampus and subcortex. In some instances, glial cells are also affected by inclusion body formation. In motor neurone disease (MND), TDP-43 or FUS inclusions can present within motor neurons of the brain stem and spinal cord. This present paper attempts to critically examine the role of such proteins in the pathogenesis of FTLD and MND as to whether they might exert a direct pathogenetic effect (gain of function), or simply act as relatively innocent witnesses to a more fundamental loss of function effect. We conclude that although there is strong evidence for both gain and loss of function effects in respect of each of the proteins concerned, in reality, it is likely that each is a single face of either side of the coin, and that both will play separate, though complementary, roles in driving the damage which ultimately leads to the downfall of neurons and clinical expression of disease. © 2012 Springer-Verlag.

Author Keywords
Frontotemporal lobar degeneration;  FUS;  Gain of function;  Loss of function;  Microtubule associated protein;  Motor neurone disease;  Tau;  TDP-43

Document Type: Article in Press
Source: Scopus

 

McNeely, M.E.a b , Earhart, G.M.a c d
Medication and subthalamic nucleus deep brain stimulation similarly improve balance and complex gait in Parkinson disease
(2012) Parkinsonism and Related Disorders, . Article in Press. 

a Program in Physical Therapy, Washington University in St. Louis, USA
b Program in Neuroscience, Division of Biology and Biomedical Sciences, Washington University in St. Louis, USA
c Department of Anatomy and Neurobiology, Washington University in St. Louis, USA
d Department of Neurology, Washington University in St. Louis, USA

Abstract
Background: Dopaminergic medications and subthalamic nucleus deep brain stimulation (STN-DBS) alleviate motor symptoms in Parkinson disease, but balance and gait are more variably affected. Balance reports are particularly inconsistent. Further, despite their prevalence in daily life, complex gait situations including backward and dual task gait are rarely studied. We aimed to assess how medications, STN-DBS, and both therapies combined affect balance and complex gait. Methods: Twelve people with Parkinson disease were evaluated OFF medication with STN-DBS OFF and ON as well as ON medication with STN-DBS OFF and ON. Motor impairment was measured with the Movement Disorder Society Unified Parkinson Disease Rating Scale motor section (MDS-UPDRS-III). The Mini-Balance Evaluations Systems Test, timed-up-and-go, and dual task timed-up-and-go measured balance and mobility. Preferred-pace forward, fast as possible forward, backward, dual task forward, and dual task backward gait were also analyzed. Results: Medication improved MDS-UPDRS-III scores, dual task timed-up-and-go, and stride length across all gait tasks. STN-DBS improved MDS-UPDRS-III scores, balance scores, dual task timed-up-and-go, and stride length and velocity across all gait tasks. Medication and STN-DBS combined did not provide additional benefits over either therapy alone. Conclusions: Overall, dopaminergic medications and STN-DBS provided similar improvements in balance and gait tasks, although the effects of STN-DBS were stronger, potentially due to reductions in medication doses after surgery. Lack of synergistic effect of treatments may suggest both therapies improve balance and gait by influencing similar neural pathways. © 2012 Elsevier Ltd. All rights reserved.

Author Keywords
Balance;  Deep brain stimulation;  Gait;  Medication;  Parkinson disease

Document Type: Article in Press
Source: Scopus

 

Oslowski, C.M.b , Hara, T.a b e , O'Sullivan-Murphy, B.b , Kanekura, K.a b , Lu, S.a b , Hara, M.a b , Ishigaki, S.f , Zhu, L.J.b , Hayashi, E.b , Hui, S.T.g , Greiner, D.c d , Kaufman, R.J.h , Bortell, R.c d , Urano, F.a b c
Thioredoxin-interacting protein mediates ER stress-induced β cell death through initiation of the inflammasome
(2012) Cell Metabolism, 16 (2), pp. 265-273. 

a Division of Endocrinology, Metabolism and Lipid Research, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, United States
b Program in Gene Function and Expression, University of Massachusetts Medical School, Worcester, MA 01605, United States
c Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, United States
d Diabetes Center of Excellence, University of Massachusetts Medical School, Worcester, MA 01605, United States
e Cardiovascular-Metabolics Research Laboratories, Daiichi Sankyo, Tokyo 140-8710, Japan
f Department of Neurology, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan
g Department of Medicine, University of California Los Angeles, Los Angeles, CA 90095, United States
h Degenerative Disease Research Program, Neuroscience, Aging, and Stem Cell Research Center, Sanford-Burnham Medical Research Institute, San Diego, CA 92037, United States

Abstract
Recent clinical and experimental evidence suggests that endoplasmic reticulum (ER) stress contributes to the life-and-death decisions of β cells during the progression of type 1 and type 2 diabetes. Although crosstalk between inflammation and ER stress has been suggested to play a significant role in β cell dysfunction and death, a key molecule connecting ER stress to inflammation has not been identified. Here we report that thioredoxin- interacting protein (TXNIP) is a critical signaling node that links ER stress and inflammation. TXNIP is induced by ER stress through the PERK and IRE1 pathways, induces IL-1β mRNA transcription, activates IL-1β production by the NLRP3 inflammasome, and mediates ER stress-mediated β cell death. Collectively, our results suggest that TXNIP is a potential therapeutic target for diabetes and ER stress-related human diseases such as Wolfram syndrome. © 2012 Elsevier Inc.

Document Type: Article
Source: Scopus

 

De Filette, M.a , Ulbert, S.b , Diamond, M.S.c , Sanders, N.N.a
Recent progress in West Nile virus diagnosis and vaccination
(2012) Veterinary Research, 43 (1), art. no. 16, . 

a Laboratory of Gene Therapy, Faculty of Veterinary Sciences, Ghent University, Heidestraat 19, 9820 Merelbeke, Belgium
b Vaccine Technologies Unit, Fraunhofer Institute for Cell Therapy and Immunology, Perlickstrasse 1, D-04103 Leipzig, Germany
c Department of Medicine, Molecular Microbiology and Pathology, Washington University, School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, United States

Abstract
West Nile virus (WNV) is a positive-stranded RNA virus belonging to the Flaviviridae family, a large family with 3 main genera (flavivirus, hepacivirus and pestivirus). Among these viruses, there are several globally relevant human pathogens including the mosquito-borne dengue virus (DENV), yellow fever virus (YFV), Japanese encephalitis virus (JEV) and West Nile virus (WNV), as well as tick-borne viruses such as tick-borne encephalitis virus (TBEV). Since the mid-1990s, outbreaks of WN fever and encephalitis have occurred throughout the world and WNV is now endemic in Africa, Asia, Australia, the Middle East, Europe and the Unites States. This review describes the molecular virology, epidemiology, pathogenesis, and highlights recent progress regarding diagnosis and vaccination against WNV infections. © 2012 De Filette et al; licensee BioMed Central Ltd.

Document Type: Review
Source: Scopus

 

Naveh-Benjamin, M.a , Maddox, G.B.b , Jones, P.a , Old, S.a , Kilb, A.a
The effects of emotional arousal and gender on the associative memory deficit of older adults
(2012) Memory and Cognition, 40 (4), pp. 551-566. 

a McAlester Hall, Department of Psychological Sciences, University of Missouri, Columbia, MO 65211, United States
b Washington University in St. Louis, St. Louis, MO, United States

Abstract
In this study we assessed the potential moderating roles of stimulus type (emotionally arousing) and participants' characteristics (gender) in older adults' associative memory deficit. In two experiments, young and older participants studied lists that included neutral and emotionally arousing word pairs (positive and negative) and completed recognition tests for the words and their associations. In Experiment 1, the majority of the word pairs were composed of two nouns, whereas in Experiment 2 they were composed of adjective-noun pairs. The results extend evidence for older adults' associative deficit and suggest that older and younger adults' item memory is improved for emotionally arousing words. However, associative memory for the word pairs did not benefit (and even showed a slight decline) from emotionally arousing words, which was the case for both younger and older adults. In addition, in these experiments, gender appeared to moderate the associative deficit of older adults, with older males but not females demonstrating this deficit. © 2011 Psychonomic Society, Inc.

Author Keywords
Aging;  Arousal;  Associative memory;  Episodic memory;  Gender

Document Type: Article
Source: Scopus

 

Robinson, G.a b c , Parker, M.a d , Kranenburg, T.A.a b , Lu, C.a e , Chen, X.a d , Ding, L.a e f , Phoenix, T.N.a b , Hedlund, E.a d , Wei, L.a d g , Zhu, X.a b , Chalhoub, N.a b , Baker, S.J.a b , Huether, R.a d h , Kriwacki, R.a h , Curley, N.a b , Thiruvenkatam, R.a b , Wang, J.a i , Wu, G.a d , Rusch, M.a d , Hong, X.a e , Becksfort, J.a i , Gupta, P.a i , Ma, J.a g , Easton, J.a d , Vadodaria, B.a d , Onar-Thomas, A.a j , Lin, T.a j , Li, S.a j , Pounds, S.a j , Paugh, S.k , Zhao, D.a i , Kawauchi, D.a l , Roussel, M.F.a l , Finkelstein, D.a d , Ellison, D.W.a g , Lau, C.C.a m , Bouffet, E.a n , Hassall, T.a o , Gururangan, S.a p , Cohn, R.a q , Fulton, R.S.a e f , Fulton, L.L.a e f , Dooling, D.J.a e f , Ochoa, K.a e f , Gajjar, A.a c , Mardis, E.R.a e f r , Wilson, R.K.a e f s , Downing, J.R.a g , Zhang, J.a d , Gilbertson, R.J.a b c
Novel mutations target distinct subgroups of medulloblastoma
(2012) Nature, 487 (7409), pp. 43-48. 

a St Jude Children's Research Hospital, Washington University Pediatric Cancer Genome Project, Memphis, TN 38105, United States
b Department of Developmental Neurobiology, St Jude Children's Research Hospital, Memphis, TN 38105, United States
c Department of Oncology, St Jude Children's Research Hospital, Memphis, TN 38105, United States
d Department of Computational Biology and Bioinformatics, St Jude Children's Research Hospital, Memphis, TN 38105, United States
e Genome Institute, Washington University School of Medicine in St Louis, St Louis, MO 63108, United States
f Department of Genetics, Washington University School of Medicine in St Louis, St Louis, MO 63108, United States
g Department of Pathology, St Jude Children's Research Hospital, Memphis, TN 38105, United States
h Department of Structural Biology, St Jude Children's Research Hospital, Memphis, TN 38105, United States
i Department of Information Sciences, St Jude Children's Research Hospital, Memphis, TN 38105, United States
j Department of Biostatistics, St Jude Children's Research Hospital, Memphis, TN 38105, United States
k Department of Pharmaceutical Sciences, St Jude Children's Research Hospital, Memphis, TN 38105, United States
l Department of Tumour Biology and Genetics, St Jude Children's Research Hospital, Memphis, TN 38105, United States
m Texas Children's Cancer and Hematology Centers, 6701 Fannin Street, Houston, TX 77030, United States
n Hospital for Sick Children, 555 University Avenue, Toronto, ON M5G 1X8, Canada
o Royal Children's Hospital, 50 Flemington Road, Parkville, VIC 3052, Australia
p Duke University Medical Center, Durham, NC 27710, United States
q School of Women's and Children's Health, University of New South Wales, Kensington, NSW 2052, Australia
r Siteman Cancer Center, Washington University School of Medicine in St Louis, St Louis, MO 63108, United States
s Department of Medicine, Washington University School of Medicine in St Louis, St Louis, MO 63108, United States

Abstract
Medulloblastoma is a malignant childhood brain tumour comprising four discrete subgroups. Here, to identify mutations that drive medulloblastoma, we sequenced the entire genomes of 37 tumours and matched normal blood. One-hundred and thirty-six genes harbouring somatic mutations in this discovery set were sequenced in an additional 56 medulloblastomas. Recurrent mutations were detected in 41 genes not yet implicated in medulloblastoma; several target distinct components of the epigenetic machinery in different disease subgroups, such as regulators of H3K27 and H3K4 trimethylation in subgroups 3 and 4 (for example, KDM6A and ZMYM3), and CTNNB1-associated chromatin re-modellers in WNT-subgroup tumours (for example, SMARCA4 and CREBBP). Modelling of mutations in mouse lower rhombic lip progenitors that generate WNT-subgroup tumours identified genes that maintain this cell lineage (DDX3X), as well as mutated genes that initiate (CDH1) or cooperate (PIK3CA) in tumorigenesis. These data provide important new insights into the pathogenesis of medulloblastoma subgroups and highlight targets for therapeutic development. © 2012 Macmillan Publishers Limited. All rights reserved.

Document Type: Article
Source: Scopus

 

Northcott, P.A.a b , Shih, D.J.H.a c , Peacock, J.a c , Garzia, L.a , Sorana Morrissy, A.a , Zichner, T.d , Stútz, A.M.d , Korshunov, A.e , Reimand, J.f , Schumacher, S.E.g , Beroukhim, R.g h i j k l , Ellison, D.W.m , Marshall, C.R.n , Lionel, A.C.o , MacK, S.a c , Dubuc, A.a c , Yao, Y.a c , Ramaswamy, V.a c , Luu, B.a , Rolider, A.a , Cavalli, F.M.G.a , Wang, X.a c , Remke, M.a , Wu, X.a , Chiu, R.Y.B.p , Chu, A.p , Chuah, E.p , Corbett, R.D.p , Hoad, G.R.p , Jackman, S.D.p , Li, Y.p , Lo, A.p , Mungall, K.L.p , Ming Nip, K.p , Qian, J.Q.p , Raymond, A.G.J.p , Thiessen, N.p , Varhol, R.J.p , Birol, I.p , Moore, R.A.p , Mungall, A.J.p , Holt, R.q , Kawauchi, D.r , Roussel, M.F.r , Kool, M.b , Jones, D.T.W.b , Witt, H.s t , Fernandez-L, A.u , Kenney, A.M.v w , Wechsler-Reya, R.J.x , Dirks, P.y , Aviv, T.z , Grajkowska, W.A.aa , Perek-Polnik, M.ab , Haberler, C.C.ac , Delattre, O.ad , Reynaud, S.S.ae , Doz, F.F.af , Pernet-Fattet, S.S.ag , Cho, B.-K.ah , Kim, S.-K.ah , Wang, K.-C.ah , Scheurlen, W.ai , Eberhart, C.G.aj , Fèvre-Montange, M.ak , Jouvet, A.al , Pollack, I.F.am , Fan, X.an , Muraszko, K.M.ao , Yancey Gillespie, G.ap , Di Rocco, C.aq , Massimi, L.aq , Michiels, E.M.C.ar , Kloosterhof, N.K.d as , French, P.J.as , Kros, J.M.at , Olson, J.M.au av , Ellenbogen, R.G.aw , Zitterbart, K.ax ay , Kren, L.az , Thompson, R.C.v , Cooper, M.K.ba , Lach, B.bb bc , McLendon, R.E.bd , Bigner, D.D.bd , Fontebasso, A.be , Albrecht, S.bf bg , Jabado, N.be bh , Lindsey, J.C.bi , Bailey, S.bi , Gupta, N.bj , Weiss, W.A.bk , Bognár, L.bl , Klekner, A.bl , Van Meter, T.E.bm , Kumabe, T.bn , Tominaga, T.bn , Elbabaa, S.K.bo , Leonard, J.R.bp , Rubin, J.B.bq , Liau, L.M.br , Van Meir, E.G.bs , Fouladi, M.bt , Nakamura, H.bu , Cinalli, G.bv , Garami, M.bw , Hauser, P.bw , Saad, A.G.bx , Iolascon, A.by bz , Jung, S.ca , Carlotti, C.G.cb , Vibhakar, R.cc , Shin Ra, Y.cd , Robinson, S.ce cf , Zollo, M.by bz , Faria, C.C.cg ch , Chan, J.A.ci , Levy, M.L.cj , Sorensen, P.H.B.ck , Meyerson, M.h , Pomeroy, S.L.cl , Cho, Y.-J.cm , Bader, G.D.f n cn co , Tabori, U.cp , Hawkins, C.E.cq , Bouffet, E.cp , Scherer, S.W.n o , Rutka, J.T.y , Malkin, D.cp cr , Clifford, S.C.bi , Jones, S.J.M.p , Korbel, J.O.d , Pfister, S.M.b s , Marra, M.A.q cs , Taylor, M.D.a c y
Subgroup-specific structural variation across 1,000 medulloblastoma genomes
(2012) Nature, 487 (7409), pp. 49-56. 

a Developmental and StemCell Biology Program, Hospital for Sick Children, 101 College Street, Toronto, ON M5G 1L7, Canada
b Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany
c Department of Laboratory Medicine and Pathobiology, University of Toronto, Medical Sciences Buildings, 1 King's College Circle, Toronto, ON M5S 1A8, Canada
d Genome Biology, European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany
e CCU Neuropathology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 220-221, Germany
f Donnelly Centre, University of Toronto, 160 College Street, Toronto, ON M5S 3E1, Canada
g Department of Cancer Biology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, United States
h Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, United States
i Department of Medicine, Harvard Medical School, 25 Shattuck Street, Boston, MA 02115, United States
j Department of Medicine, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, United States
k Cancer Program, Broad Institute, 7 Cambridge Center, Cambridge, MA 02142, United States
l Center for Cancer Genome Discovery, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, United States
m Department of Pathology, St Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105, United States
n McLaughlin Centre, Department of Molecular Genetics, University of Toronto, 101 College Street, Toronto, ON M5G 1L7, Canada
o Centre for Applied Genomics and Program in Genetics and Genome Biology, Hospital for Sick Children, 101 College Street, Toronto, ON M5G 1L7, Canada
p Michael Smith Genome Sciences Centre, BC Cancer Agency, 100-570 West 7th Avenue, Vancouver, BC V5Z 4S6, Canada
q Michael Smith Genome Sciences Centre, BC Cancer Agency, 675 West 10th Avenue, Vancouver, BC V5Z 1L3, Canada
r Tumour Cell Biology, St Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105, United States
s Department of Pediatric Oncology, University Hospital Heidelberg, Im Neuenheimer Feld 430, 69120 Heidelberg, Germany
t Departments of Hematology and Immunology, University Hospital Heidelberg, Im Neuenheimer Feld 430, 69120 Heidelberg, Germany
u Pediatric Clinical Trials Office, Memorial Sloan-Kettering Cancer Center, 405 Lexington Avenue, New York, NY 10174, United States
v Neurological Surgery, Vanderbilt Medical Center, T-4224 MCN, Nashville, TN 37232-2380, United States
w Cancer Biology, Vanderbilt Medical Center, MRB III 6160, 465 21st Avenue South, Nashville, TN 37232-8550, United States
x Sanford-BurnhamMedical Research Institute, San Diego, CA 92037, United States
y Department of Surgery, Division of Neurosurgery and Labatt Brain Tumour Research Centre, Hospital for Sick Children, 555 University Avenue, Hill 1503, Toronto, ON M5G 1X8, Canada
z Developmental and Stem Cell Biology Program, Hospital for Sick Children, TMDT-13-601, 101 College Street, Toronto, ON M5G 1L7, Canada
aa Department of Pathology, Children's Memorial Health Institute, Aleja Dzieci Polskich 20, 04-730 Warsaw, Poland
ab Department of Oncology, Children's Memorial Health Institute, Aleja Dzieci Polskich 20, 04-730 Warsaw, Poland
ac Institute of Neurology, Medical University of Vienna, AKH 4J, Waehringer Gürtel 18-20, A-1097 Vienna, Austria
ad INSERMU 830, Institut Curie, 26 rue d'Ulm, 75238 Paris Cedex 5, France
ae Unit of Somatic Genetics, Institut Curie, 26 rue d'Ulm, 75238 Paris Cedex 5, France
af Department of Pediatric Oncology, Institut Curie, 26 rue d'Ulm, 75248 Paris Cedex 5, France
ag Pediatric Hematology and Oncology, CHUV University Hospital, 1011 Lausanne, Switzerland
ah Department of Neurosurgery, Division of Pediatric Neurosurgery, Seoul National University Children's Hospital, 101 Daehak-Ro Jongno-Gu, Seoul 110-744, South Korea
ai Cnopf´sche Kinderklinik, Theodor-Kutzer-Ufer 1-3, 90419 Nuremberg, Germany
aj Departments of Pathology, Ophthalmology and Oncology, John Hopkins University School of Medicine, Ross Building 558, 720 Rutland Avenue, Baltimore, MD 21205, United States
ak INSERM U1028, CNRS UMR5292, Université de Lyon, 69336 Lyon, France
al Centre de Pathologie EST, Groupement Hospitalier EST, Universite de Lyon, 69500 Bron, France
am Department of Neurological Surgery, University of Pittsburgh School of Medicine, 4401 Penn Avenue, Pittsburgh, PA 15224, United States
an Departments of Neurosurgery and Cell and Developmental Biology, University of Michigan Medical School, 5018 BSRB, 109 Zina Pitcher Place, Ann Arbor, MI 48109, United States
ao Department of Neurosurgery, University of Michigan Medical School, Taubman Center, 1500 E.Medical Center Drive, Ann Arbor, MI 48109, United States
ap Department of Surgery, Division of Neurosurgery, University of Alabama at Birmingham, 1900 University Boulevard, Birmingham, AB 35294-0006, United States
aq Department of Pediatric Neurosurgery, Catholic University Medical School, 00186 Rome, Italy
ar Department of Pediatric Oncology and Hematology, Erasmus Medical Center, Dr. Molewaterplein 50, 3000 Rotterdam, Netherlands
as Department of Neurology, Erasmus Medical Center, Dr. Molewaterplein 50, 3000 CA Rotterdam, Netherlands
at Department of Pathology, Erasmus Medical Center, Dr. Molewaterplein 50, 3015 GE Rotterdam, Netherlands
au Clinical Research Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, Seattle, WA 98109, United States
av Seattle Children's Hospital, Seattle, WA 98104, United States
aw Neurological Surgery, University of Washington School of Medicine, Harborview Medical Center, 325 Ninth Avenue, Seattle, WA 98104, United States
ax Department of Pediatric Oncology, School of Medicine, Masaryk University, Cernopolni 9, 613 00 Brno, Czech Republic
ay Department of Pediatric Oncology, University Hospital Brno, 625 00 Brno, Czech Republic
az Department of Pathology, University Hospital Brno, Jihlavska 20, 625 00 Brno, Czech Republic
ba Department of Neurology, Vanderbilt Medical Center, MRB III 6160, 465 21st Avenue South, Nashville, TN 37232-8550, United States
bb Department of Pathology and Molecular Medicine, Division of Anatomical Pathology, McMasterUniversity, Hamilton, ON L8S4L8, Canada
bc Department of Pathologyand Laboratory Medicine, Hamilton General Hospital, 237 Barton Street East, Hamilton, ON L8L 2X2, Canada
bd Department of Pathology, Duke University, DUMC 3712, Durham, NC 27710, United States
be Division of Experimental Medicine, McGill University, 4060 Ste Catherine West, Montreal, QC H3Z 2Z3, Canada
bf Department of Pathology, McGill University, Montreal, QC H3A 2B4, Canada
bg Department of Pathology, Montreal Children's Hospital, 2300 Tupper, Montreal, QC H3H 1P3, Canada
bh Department of Pediatrics, Division of Hemato-Oncology, McGill University, Montreal, QC H3H1P3, Canada
bi Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne NE1 4LP, United Kingdom
bj Departments of Neurological Surgery and Pediatrics, University of California San Francisco, 505 Parnassus Avenue, San Francisco, CA 94143-0112, United States
bk Departments of Neurology, Pediatrics, and Neurosurgery, University of California San Francisco, Helen Diller Family Cancer Research Building, 1450 3rd Street, San Francisco, CA 94158, United States
bl Department of Neurosurgery, University of Debrecen, Medical and Health Science Centre, Móricz Zs. Krt. 22., 4032 Debrecen, Hungary
bm Pediatrics, Virginia Commonwealthy University, School of Medicine, Box 980646, Pediatric Hematology-Oncology, 1101 East Marshall Street, Richmond, VA 23298-0646, United States
bn Department OfNeurosurgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan
bo Department of Neurosurgery, Division of Pediatric Neurosurgery, St Louis University School of Medicine, 1465 South Grand Boulevard, St Louis, MO 63104, United States
bp Department of Neurosurgery, Division of Pediatric Neurosurgery, Washington University School of Medicine and St Louis Children's Hospital, 660 South Euclid Avenue, St Louis, MO 63110, United States
bq Departments of Pediatrics, Anatomy and Neurobiology, Washington University School of Medicine and St Louis Children's Hospital, Campus Box 8208, 660 South Euclid Avenue, St Louis, MO 63110, United States
br Department of Neurosurgery, David Geffen School of Medicine at UCLA, Campus 690118, 10833 Le Conte Avenue, Los Angeles, CA 90095, United States
bs Laboratory of Molecular Neuro-Oncology, Departments of Neurosurgery and Hematology and MedicalOncology, Emory University, 1365C Clifton Road NE, Atlanta, GA 30322, United States
bt Division of Oncology, University of Cincinnati, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, United States
bu Department of Neurosurgery, Kumamoto University Graduate School of Medical Science, 1-1-1, Honjo, Kumamoto 860-8556, Japan
bv Paediatric Neurosurgery, Ospedale Santobono-Pausilipon, 80145 Naples, Italy
bw 2nd Department of Pediatrics, Semmelweis University, 1085 Budapest, Hungary
bx Department of Pathology, University of Arkansas for Medical Sciences, 1 Children's Way, Little Rock, AR 72202, United States
by Dipartimento di Biochimica e Biotecnologie Mediche, University of Naples, Via Pansini 5, 80145 Naples, Italy
bz CEINGE Biotecnologie Avanzate, Via Gaetano Salvatore 486, 80145 Naples, Italy
ca Department of Neurosurgery, Chonnam National University Research Institute of Medical Sciences, Chonnam National University Hwasun Hospital and Medical School, 322 Seoyang-ro, Hwasun-eup, Hwasun-gun, Chonnam 519-763, South Korea
cb Department of Surgery and Anatomy, Faculty of Medicine of Ribeirão Preto, Universidade de São Paulo, Brazil, Avenida Bandeirantes, 3900, Monte Alegre, 14049-900, Rebeirao Preto, São Paulo, Brazil
cc Department of Pediatrics, University of Colorado Denver, 12800 19th Avenue, Aurora, CO 80045, United States
cd Department of Neurosurgery, University of Ulsan, Asan Medical Center, Seoul, 138-736, South Korea
ce Division of Pediatric Neurosurgery, Case Western Reserve, Cleveland, OH 44106, United States
cf Rainbow Babies and Children's, Cleveland, OH 44106, United States
cg Division of Neurosurgery, Hospital de Santa Maria, Centro Hospitalar Lisboa Norte EPE, 1169-050, Lisbon, Portugal
ch Cell Biology Program, Hospital for Sick Children, TMDT-401-J, 101 College Street, Toronto, ON M5G1L7, Canada
ci Department of Pathology, Laboratory Medicine, University of Calgary, 3330 Hospital Drive NW, Calgary, AB T2N 4N1, Canada
cj UCSD Division of Neurosurgery, Rady Children's Hospital San Diego, 8010 Frost Street, San Diego, CA 92123, United States
ck Department of Molecular Oncology, British Columbia Cancer Research Centre, 675 West 10th Avenue, Vancouver, BC V5Z 1L3, Canada
cl Department of Neurology, Harvard Medical School, Children's Hospital Boston, Fegan 11, 300 Longwood Avenue, Boston, MA 02115, United States
cm Department of Neurology and Neurological Sciences, Stanford University School of Medicine, MSLS Building, 1201 Welch Road, Stanford, CA 94305, United States
cn Banting and Best Department of Medical Research, University of Toronto, Toronto, ON M5G 1L6, Canada
co Samuel Lunenfeld Research Institute, Mount Sinai Hospital, University of Toronto, Toronto M5G1X5, ON, Canada
cp Department of Haematology and Oncology, Hospital for Sick Children, 555 University Avenue, Toronto, ON M5G 1X8, Canada
cq Department of Pathology, Hospital for Sick Children, 555 University Avenue, Toronto, ON M5G 1X8, Canada
cr Department of Pediatrics, University of Toronto, Toronto, ON M5G 1X8, Canada
cs Department of Medical Genetics, University of British Columbia, 675 West 10th Avenue, Vancouver, BC V5Z 1L3, Canada

Abstract
Medulloblastoma, the most common malignant paediatric brain tumour, is currently treated with nonspecific cytotoxic therapies including surgery, whole-brain radiation, and aggressive chemotherapy. As medulloblastoma exhibits marked intertumoural heterogeneity, with at least four distinct molecular variants, previous attempts to identify targets for therapy have been underpowered because of small samples sizes. Here we report somatic copy number aberrations (SCNAs) in 1,087 unique medulloblastomas. SCNAs are common in medulloblastoma, and are predominantly subgroup-enriched. The most common region of focal copy number gain is a tandem duplication of SNCAIP, a gene associated with Parkinson's disease, which is exquisitely restricted to Group 4α. Recurrent translocations of PVT1, including PVT1-MYC and PVT1-NDRG1, that arise through chromothripsis are restricted to Group 3. Numerous targetable SCNAs, including recurrent events targeting TGF-β signalling in Group 3, and NF-κB signalling in Group 4, suggest future avenues for rational, targeted therapy. © 2012 Macmillan Publishers Limited. All rights reserved.

Document Type: Article
Source: Scopus

 

Loitman, J.E.
Association of mental health disorders with opioid use and abuse in Veterans of Iran and Afghanistan
(2012) Journal of Pain and Symptom Management, 44 (2), pp. 316-317. 

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

Document Type: Note
Source: Scopus

 

Grant, J.D.a , Scherrer, J.F.a b , Lynskey, M.T.a , Agrawal, A.a , Duncan, A.E.a c , Haber, J.R.d , Heath, A.C.a , Bucholz, K.K.a
Associations of Alcohol, Nicotine, Cannabis, and Drug Use/Dependence with Educational Attainment: Evidence from Cotwin-Control Analyses
(2012) Alcoholism: Clinical and Experimental Research, 36 (8), pp. 1412-1420. 

a Midwest Alcoholism Research Center at Washington University, Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, United States
b Research Service (151-JC), St. Louis Veterans Administration Medical Center, St. Louis, MO, United States
c George Warren Brown School of Social Work, Washington University, St. Louis, MO, United States
d Palo Alto Veterans Affairs Health Care System, Menlo Park, CA, United States

Abstract
Background: Although substance use is associated with reduced educational attainment, this association may be owing to common risk factors such as socioeconomic disadvantage. We tested whether alcohol, nicotine, and illicit drug use and dependence were associated with lifetime educational attainment after controlling for familial background characteristics. Methods: Data were from a 1987 questionnaire and a 1992 telephone diagnostic interview of 6,242 male twins (n = 3,121 pairs; mean age = 41.9 years in 1992) who served in the U.S. military during the Vietnam era and therefore, were eligible for educational benefits after military service. Reduced educational attainment (<16 years) was examined in twin pairs discordant for substance use history. Substance use and dependence risk factors assessed were early alcohol and cannabis use, daily nicotine use, lifetime cannabis use, and alcohol, nicotine, cannabis, and any illicit drug dependence. Results: Three significant differences were observed between at-risk twins and their cotwins: Compared to their low-risk cotwins, likelihood of completing <16 years of education was significantly increased for the following: (i) twins who used alcohol before age 18 (adjusted OR = 1.44; 95% CI: 1.02 to 2.05), (ii) twins with a lifetime alcohol dependence diagnosis (adjusted OR = 1.76; 95% CI: 1.27 to 2.44), and (iii) twins who had used nicotine daily for 30 or more days (adjusted OR = 2.54, 95% CI: 1.55 to 4.17). However, no differences in education were observed among twin pairs discordant for cannabis initiation, early cannabis use, or cannabis, nicotine, or any illicit drug dependence. Conclusions: Even in a veteran population with access to military educational benefits, early alcohol use, alcohol dependence, and daily nicotine use remained significantly associated with years of education after controlling for shared familial contributions to educational attainment. The association between other substances and educational attainment was explained by familial factors common to these substance use phenotypes and adult educational attainment. © 2012 by the Research Society on Alcoholism.

Author Keywords
Alcohol dependence;  Cotwin-control design;  Drug dependence;  Early substance use;  Educational attainment

Document Type: Article
Source: Scopus

 

Onken, M.D.a , Worley, L.A.a , Char, D.H.b , Augsburger, J.J.c , Correa, Z.M.c , Nudleman, E.a , Aaberg Jr., T.M.d , Altaweel, M.M.e , Bardenstein, D.S.f , Finger, P.T.g , Gallie, B.L.h , Harocopos, G.J.a , Hovland, P.G.i , McGowan, H.D.h , Milman, T.j , Mruthyunjaya, P.k , Simpson, E.R.h , Smith, M.E.a , Wilson, D.J.l , Wirostko, W.J.m , Harbour, J.W.a
Collaborative ocular oncology group report number 1: Prospective validation of a multi-gene prognostic assay in uveal melanoma
(2012) Ophthalmology, 119 (8), pp. 1596-1603. 

a Washington University, Siteman Cancer Center, St. Louis, MO, United States
b Tumori Foundation, San Francisco, CA, United States
c University of Cincinnati College of Medicine, Cincinnati, OH, United States
d Michigan State University, East Lansing, MI, United States
e University of Wisconsin, Madison, WI, United States
f Case Western Reserve University, Cleveland, OH, United States
g New York Eye Cancer Center, New York, NY, United States
h University of Toronto, Toronto, Canada
i Colorado Retina Associates, Denver, CO, United States
j New York Eye and Ear Infirmary, New York, NY, United States
k Duke University, Durham, NC, United States
l Oregon Health and Science University, Portland, OR, United States
m Medical College of Wisconsin, Milwaukee, WI, United States

Abstract
Purpose: This study evaluates the prognostic performance of a 15 gene expression profiling (GEP) assay that assigns primary posterior uveal melanomas to prognostic subgroups: class 1 (low metastatic risk) and class 2 (high metastatic risk). Design: Prospective, multicenter study. Participants: A total of 459 patients with posterior uveal melanoma were enrolled from 12 independent centers. Testing: Tumors were classified by GEP as class 1 or class 2. The first 260 samples were also analyzed for chromosome 3 status using a single nucleotide polymorphism assay. Net reclassification improvement analysis was performed to compare the prognostic accuracy of GEP with the 7th edition clinical Tumor-Node-Metastasis (TNM) classification and chromosome 3 status. Main Outcome Measures: Patients were managed for their primary tumor and monitored for metastasis. Results: The GEP assay successfully classified 446 of 459 cases (97.2%). The GEP was class 1 in 276 cases (61.9%) and class 2 in 170 cases (38.1%). Median follow-up was 17.4 months (mean, 18.0 months). Metastasis was detected in 3 class 1 cases (1.1%) and 44 class 2 cases (25.9%) (log-rank test, P&lt;10 -14). Although there was an association between GEP class 2 and monosomy 3 (Fisher exact test, P&lt;0.0001), 54 of 260 tumors (20.8%) were discordant for GEP and chromosome 3 status, among which GEP demonstrated superior prognostic accuracy (log-rank test, P = 0.0001). By using multivariate Cox modeling, GEP class had a stronger independent association with metastasis than any other prognostic factor (P&lt;0.0001). Chromosome 3 status did not contribute additional prognostic information that was independent of GEP (P = 0.2). At 3 years follow-up, the net reclassification improvement of GEP over TNM classification was 0.43 (P = 0.001) and 0.38 (P = 0.004) over chromosome 3 status. Conclusions: The GEP assay had a high technical success rate and was the most accurate prognostic marker among all of the factors analyzed. The GEP provided a highly significant improvement in prognostic accuracy over clinical TNM classification and chromosome 3 status. Chromosome 3 status did not provide prognostic information that was independent of GEP. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references. © 2012 American Academy of Ophthalmology.

Document Type: Article
Source: Scopus

 

Dewan, V.a , Lambert, D.a b , Edler, J.a b , Kymes, S.a b , Apte, R.S.a
Cost-effectiveness analysis of ranibizumab plus prompt or deferred laser or triamcinolone plus prompt laser for diabetic macular edema
(2012) Ophthalmology, 119 (8), pp. 1679-1684. 

a Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, MO, United States
b Center for Economic Evaluation in Medicine, Washington University School of Medicine, St. Louis, MO, United States

Abstract
Objective: Perform a cost-effectiveness analysis of the treatment of diabetic macular edema (DME) with ranibizumab plus prompt or deferred laser versus triamcinolone plus prompt laser. Data for the analysis were drawn from reports of the Diabetic Retinopathy Clinical Research Network (DRCRnet) Protocol I. Design: Computer simulation based on Protocol I data. Analyses were conducted from the payor perspective. Participants: Simulated participants assigned characteristics reflecting those seen in Protocol I. Methods: Markov models were constructed to replicate Protocol I's 104-week outcomes using a microsimulation approach to estimation. Baseline characteristics, visual acuity (VA), treatments, and complications were based on Protocol I data. Costs were identified by literature search. One-way sensitivity analysis was performed, and the results were validated against Protocol I data. Main Outcome Measures: Direct cost of care for 2 years, change in VA from baseline, and incremental cost-effectiveness ratio (ICER) measured as cost per additional letter gained from baseline (Early Treatment of Diabetic Retinopathy Study). Results: For sham plus laser (S+L), ranibizumab plus prompt laser (R+pL), ranibizumab plus deferred laser (R+dL), and triamcinolone plus laser (T+L), effectiveness through 104 weeks was predicted to be 3.46, 7.07, 8.63, and 2.40 letters correct, respectively. The ICER values in terms of dollars per VA letter were $393 (S+L vs. T+L), $5943 (R+pL vs. S+L), and $20 (R+dL vs. R+pL). For pseudophakics, the ICER value for comparison triamcinolone with laser versus ranibizumab with deferred laser was $14 690 per letter gained. No clinically relevant changes in model variables altered outcomes. Internal validation demonstrated good similarity to Protocol I treatment patterns. Conclusions: In treatment of phakic patients with DME, ranibizumab with deferred laser provided an additional 6 letters correct compared with triamcinolone with laser at an additional cost of $19 216 over 2 years. That would indicate that if the gain in VA seen at 2 years is maintained in subsequent years, then the treatment of phakic patients with DME using ranibizumab may meet accepted standards of cost-effectiveness. For pseudophakic patients, first-line treatment with triamcinolone seems to be the most cost-effective option. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references. © 2012 American Academy of Ophthalmology.

Document Type: Article
Source: Scopus

 

Delgado Almandoz, J.E.a e , Jagadeesan, B.D.a f , Refai, D.g , Moran, C.J.a b , Cross III, D.T.a b , Chicoine, M.R.b , Rich, K.M.b , Diringer, M.N.c d , Dacey Jr., R.G.b , Derdeyn, C.P.a b c , Zipfel, G.J.b c
Diagnostic yield of computed tomography angiography and magnetic resonance angiography in patients with catheter angiography-negative subarachnoid hemorrhage: Clinical article
(2012) Journal of Neurosurgery, 117 (2), pp. 309-315. 


a Division of Neuroradiology, Mallinckrodt Institute of Radiology, Saint Louis, MO, United States
b Department of Neurological Surgery, Washington University School of Medicine, Saint Louis, MO, United States
c Department of Neurology, Washington University School of Medicine, Saint Louis, MO, United States
d Neurology/Neurosurgery Intensive Care Unit, Washington University School of Medicine, Saint Louis, MO, United States
e Division of Interventional Neuroradiology, Abbott Northwestern Hospital, 800 East 28th Street, Minneapolis, MN 55407, United States
f Division of Interventional Neuroradiology, University of Minnesota School of Medicine, Minneapolis, MN, United States
g Department of Neurological Surgery, Emory University, Atlanta, GA, United States

Abstract
Object. The yield of CT angiography (CTA) and MR angiography (MRA) in patients with subarachnoid hemorrhage (SAH) who have a negative initial catheter angiogram is currently not well understood. This study aims to determine the yield of CTA and MRA in a prospective cohort of patients with SAH and a negative initial catheter angiogram. Methods. From January 1, 2005, until September 1, 2010, the authors instituted a prospective protocol in which patients with SAH - as documented by noncontrast CT or CSF xanthochromia and a negative initial catheter angiogram - were evaluated using CTA and MRA to assess for causative cerebral aneurysms. Two neuroradiologists independently evaluated the noncontrast CT scans to determine the SAH pattern (perimesencephalic or not) and the CT and MR angiograms to assess for causative cerebral aneurysms. Results. Seventy-seven patients were included, with a mean age of 52.8 years (median 54 years, range 19-88 years). Fifty patients were female (64.9%) and 27 male (35.1%). Forty-three patients had nonperimesencephalic SAH (55.8%), 29 patients had perimesencephalic SAH (37.7%), and 5 patients had CSF xanthochromia (6.5%). Computed tomography angiography demonstrated a causative cerebral aneurysm in 4 patients (5.2% yield), all of whom had nonperimesencephalic SAH (9.3% yield). Mean aneurysm size was 2.6 mm (range 2.1-3.3 mm). Magnetic resonance angiography demonstrated only 1 of these aneurysms. No causative cerebral aneurysms were found in patients with perimesencephalic SAH or CSF xanthochromia. Conclusions. Computed tomography angiography is a valuable adjunct in the evaluation of patients with nonperimesencephalic SAH who have a negative initial catheter angiogram, demonstrating a causative cerebral aneurysm in 9.3% of patients.

Author Keywords
Aneurysm;  Catheter angiography;  Computed tomography angiography;  Magnetic resonance angiography;  Subarachnoid hemorrhage;  Vascular disorders

Document Type: Article
Source: Scopus

 

Kasliwal, M.K.a , Smith, J.S.a , Shaffrey, C.I.a , Carreon, L.Y.b , Glassman, S.D.b , Schwab, F.c , Lafage, V.c , Fu, K.-M.G.d , Bridwell, K.H.e
Does prior short-segment surgery for adult scoliosis impact perioperative complication rates and clinical outcome among patients undergoing scoliosis correction? Clinical article
(2012) Journal of Neurosurgery: Spine, 17 (2), pp. 128-133. 

a Department of Neurosurgery, University of Virginia Health System, P.O. Box 800212, Charlottesville, VA 22908, United States
b Norton Leatherman Spine Center, Louisville, KY, United States
c Hospital for Joint Diseases, NYU Langone Medical Center, New York, NY, United States
d Department of Neurosurgery, Weill Cornell Medical College, New York, NY, United States
e Spinal Deformity Service, Washington University, St. Louis, MO, United States

Abstract
Object. In many adults with scoliosis, symptoms can be principally referable to focal pathology and can be addressed with short-segment procedures, such as decompression with or without fusion. A number of patients subsequently require more extensive scoliosis correction. However, there is a paucity of data on the impact of prior short-segment surgeries on the outcome of subsequent major scoliosis correction, which could be useful in preoperative counseling and surgical decision making. The authors' objective was to assess whether prior focal decompression or short-segment fusion of a limited portion of a larger spinal deformity impacts surgical parameters and clinical outcomes in patients who subsequently require more extensive scoliosis correction surgery. Methods. The authors conducted a retrospective cohort analysis with propensity scoring, based on a prospective multicenter deformity database. Study inclusion criteria included a patient age ≥ 21 years, a primary diagnosis of untreated adult idiopathic or degenerative scoliosis with a Cobb angle ≥ 20°, and available clinical outcome measures at a minimum of 2 years after scoliosis surgery. Patients with prior short-segment surgery (< 5 levels) were propensity matched to patients with no prior surgery based on patient age, Oswestry Disability Index (ODI), Cobb angle, and sagittal vertical axis. Results. Thirty matched pairs were identified. Among those patients who had undergone previous spine surgery, 30% received instrumentation, 40% underwent arthrodesis, and the mean number of operated levels was 2.4 ± 0.9 (mean ± SD). As compared with patients with no history of spine surgery, those who did have a history of prior spine surgery trended toward greater blood loss and an increased number of instrumented levels and did not differ significantly in terms of complication rates, duration of surgery, or clinical outcome based on the ODI, Scoliosis Research Society-22r, or 12-Item Short Form Health Survey Physical Component Score (p > 0.05). Conclusions. Patients with adult scoliosis and a history of short-segment spine surgery who later undergo more extensive scoliosis correction do not appear to have significantly different complication rates or clinical improvements as compared with patients who have not had prior short-segment surgical procedures. These findings should serve as a basis for future prospective study.

Author Keywords
Adult scoliosis;  Complication;  Deformity;  Outcome;  Revision;  Surgery

Document Type: Article
Source: Scopus

 

Coppola, G.a b , Chinnathambi, S.f , Lee, J.J.a , Dombroski, B.A.g , Baker, M.C.h i j , Soto-ortolaza, A.I.h i j , Lee, S.E.c , Klein, E.a , Huang, A.Y.a , Sears, R.a , Lane, J.R.a , Karydas, A.M.c , Kenet, R.O.k , Biernat, J.f , Wang, L.g , Cotman, C.W.d , Decarli, C.S.e , Levey, A.I.l m n , Ringman, J.M.a , Mendez, M.F.a , Chui, H.C.o , Le ber, I.q r , Brice, A.q s , Lupton, M.K.t , Preza, E.t , Lovestone, S.t , Powell, J.t , Graff-radford, N.h i j , Petersen, R.C.u , Boeve, B.F.u , Lippa, C.F.v , Bigio, E.H.w , Mackenzie, I.x , Finger, E.y , Kertesz, A.y , Caselli, R.J.z , Gearing, M.l m n , Juncos, J.L.l m n , Ghetti, B.aa , Spina, S.aa , Bordelon, Y.M.a , Tourtellotte, W.W.ab , Frosch, M.P.ac , Vonsattel, J.P.G.ad ae af , Zarow, C.p , Beach, T.G.ag , Albin, R.L.ah ai aj , Lieberman, A.P.ah ai aj , Lee, V.M.g , Trojanowski, J.Q.g , Van deerlin, V.M.g , Bird, T.D.ak al am , Galasko, D.R.an ao , Masliah, E.an ao , White, C.L.ap , Troncoso, J.C.aq , Hannequin, D.ar , Boxer, A.L.c , Geschwind, M.D.c , Kumar, S.f , Mandelkow, E.f , Wszolek, Z.K.h i j , Uitti, R.J.h i j , Dickson, D.W.h i j , Haines, J.L.as , Mayeux, R.ad ae af , Pericak-vance, M.A.at au , Farrer, L.A.av aw ax ay az , Apostolova, L.G.ba , Arnold, S.E.bb , Baldwin, C.T.bc , Barber, R.bd , Barmada, M.M.be , Beach, T.bf , Beecham, G.W.bg bh , Beekly, D.bi , Bennett, D.A.bj bk , Bigio, E.H.bl , Bird, T.D.bm , Blacker, D.bn bo , Boeve, B.F.bp , Bowen, J.D.bq , Boxer, A.br , Burke, J.R.bs , Buros, J.bc , Buxbaum, J.D.bt bu bv , Cairns, N.J.bw , Cantwell, L.B.bx , Cao, C.by , Carlson, C.S.bz , Carney, R.M.ca , Carrasquillo, M.M.cb , Carroll, S.L.cc , Chui, H.C.cd , Clark, D.G.ce , Corneveaux, J.cf , Cotman, C.W.cg , Crane, P.K.ch , Cruchaga, C.ci , Cummings, J.L.ba , De Jager, P.L.cj ck , DeCarli, C.cl , DeKosky, S.T.cm , Demirci, F.Y.be , Diaz-Arrastia, R.cn , Dick, M.cg , Dickson, D.W.cb , Dombroski, B.A.bx , Duara, R.co , Ellis, W.G.cp , Ertekin-Taner, N.N.cb cq , Evans, D.cr , Faber, K.M.cs , Fallon, K.B.cc , Farlow, M.R.ct , Ferris, S.cu , Foroud, T.M.cs , Frosch, M.P.cv , Galasko, D.R.cw , Gallins, P.J.bg , Ganguli, M.cx , Gearing, M.cy cz , Geschwind, D.H.da , Ghetti, B.db , Gilbert, J.R.bg bh , Gilman, S.dc , Giordani, B.dd , Glass, J.D.de , Goate, A.M.be , Graff-Radford, N.R.cb cq , Green, R.C.bc df dg , Growdon, J.H.dh , Hakonarson, H.di , Hamilton, R.L.dj , Hardy, J.dk , Harrell, L.E.ce , Head, E.dl , Honig, L.S.dm , Huentelman, M.J.cf , Hulette, C.M.dn , Hyman, B.T.dh , Jarvik, G.P.do dp , Jicha, G.A.dq , Jin, L.-W.cp , Johnson, N.dr , Jun, G.bc ds dt , Kamboh, M.I.be du , Karlawish, J.dv , Karydas, A.br , Kauwe, J.S.K.dw , Kaye, J.A.dx dy , Kim, R.dz , Koo, E.H.cw , Kowall, N.W.df ea , Kramer, P.dx eb , Kukull, W.A.ec , Lah, J.J.de , Larson, E.B.ed , Levey, A.I.de , Lieberman, A.P.ee , Lopez, O.L.du , Lunetta, K.L.ds , Mack, W.J.ef , Marson, D.C.ba , Martin, E.R.bg bh , Martiniuk, F.eg , Mash, D.C.eh , Masliah, E.cw ei , McCormick, W.C.ch , McCurry, S.M.ej , McDavid, A.N.bz , McKee, A.C.df ea , Mesulam, M.ek el , Miller, B.L.br , Miller, C.A.em , Miller, J.W.cp , Montine, T.J.en , Morris, J.C.bw eo , Myers, A.J.ep , Naj, A.C.bg , Nowotny, P.ci , Parisi, J.E.eq er , Perl, D.P.es , Peskind, E.et , Petersen, R.C.bp , Poon, W.W.cg , Potter, H.by , Quinn, J.F.dx , Raj, A.by , Rajbhandary, R.A.dg , Raskind, M.et , Reiman, E.M.cf eu ev ew , Reisberg, B.cu ex , Reitz, C.ey fa fb , Ringman, J.M.ba , Roberson, E.D.ce , Rogaeva, E.fc , Rosenberg, R.N.cn , Sano, M.bu , Saykin, A.J.be fd , Schneider, J.A.bj fe , Schneider, L.S.cd ff , Seeley, W.br , Shelanski, M.L.fg , Slifer, M.A.bg bh , Smith, C.D.dq , Sonnen, J.A.en , Spina, S.db , George-Hyslop, P.S.fc fh , Stern, R.A.df , Tanzi, R.E.dh , Trojanowski, J.Q.bx , Troncoso, J.C.fi , Tsuang, D.W.et , Van Deerlin, V.M.bx , Vardarajan, B.N.bc , Vinters, H.V.ba fj , Vonsattel, J.P.ez , Wang, L.-S.bx , Weintraub, S.ek el , Welsh-Bohmer, K.A.bs fk , Williamson, J.dm , Woltjer, R.L.fl , Younkin, S.G.cb , Ross, O.A.h i j , Rademakers, R.h i j , Schellenberg, G.D.g , Miller, B.L.c , Mandelkow, E.f , Geschwind, D.H.a b
Evidence for a role of the rare p.A152T variant in mapt in increasing the risk for FTD-spectrum and Alzheimer's diseases
(2012) Human Molecular Genetics, 21 (15), art. no. dds161, pp. 3500-3512. 

a Department of Neurology, University of California, Los Angeles, CA, United States
b Department of Psychiatry, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, CA, United States
c Department of Neurology, University of California, San Francisco, CA, United States
d Department of Neurology, University of California, Irvine, CA, United States
e Department of Neurology, University of California, Davis, CA, United States
f DZNE, German Center for Neurodegenerative Diseases, CAESAR Research Center, Ludwig-Erhard-Str. 2, Bonn 53175, Germany
g Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA, United States
h Department of Neuroscience, Mayo Clinic Florida, Jacksonville, FL, United States
i Department of Neurology, Mayo Clinic Florida, Jacksonville, FL, United States
j Department of Pathology, Mayo Clinic Florida, Jacksonville, FL, United States
k Department of Medicine, New York Presbyterian Hospital-Weill Cornell Medical College, New York, NY, United States
l Department of Neurology, Emory University School of Medicine, Atlanta, GA, United States
m Department of Pathology, Emory University School of Medicine, Atlanta, GA, United States
n Department of Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, United States
o Department of Neurology, University of Southern California, Downey, CA, United States
p Rancho Los Amigos National Rehabilitation Center, University of Southern California, Downey, CA, United States
q Centre de Recherche de l'Institut du Cerveau et de la Moelle Epinière, UMRS975, INSERM U975, CNRS UMR 7225, Paris, France
r Centre de Référence Démences Rares, AP-HP, Hopital de la Salpetrière, F-75013, Paris, France
s Département de Génétique et Cytogénétique, AP-HP, Hopital de la Salpetrière, F-75013, Paris, France
t Institute of Psychiatry, King's College London, London, United Kingdom
u Department of Neurology, Mayo Clinic, Rochester, MN, United States
v Department of Neurology, Drexel University College of Medicine, Philadelphia, PA, United States
w Cognitive Neurology and Alzheimer Disease Center, Northwestern University Feinberg School of Medicine, Chicago, IL, United States
x Department of Pathology, University of British Columbia, Vancouver, BC, Canada
y Department of Clinical Neurological Sciences, University of Western Ontario, London, ON, Canada
z Department of Neurology, Mayo Clinic, Scottsdale, AZ, United States
aa Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, United States
ab Human Brain and Spinal Fluid Resource Center, Veterans Affairs West Los Angeles Healthcare Center, Los Angeles, CA, United States
ac C. S. Kubik Laboratory for Neuropathology, Mass General Institute for Neurodegenerative Disease, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States
ad Department of Neurology, Columbia University, New York City, NY, United States
ae Department of Pathology, Columbia University, New York City, NY, United States
af The Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New York City, NY, United States
ag Civin Laboratory for Neuropathology, Banner Sun Health Research Institute, Sun City, AZ, United States
ah Department of Neurology, University of Michigan, Ann Arbor, MI, United States
ai Department of Pathology, University of Michigan, Ann Arbor, MI, United States
aj Geriatrics Research, Education, and Clinical Center, VA Ann Arbor Health System, Ann Arbor, MI, United States
ak Department of Medicine, University of Washington, Seattle, WA, United States
al Department of Neurology, University of Washington, Seattle, WA, United States
am Department of Medical Genetics, University of Washington, Seattle, WA, United States
an Department of Pathology, University of California San Diego, La Jolla, CA, United States
ao Department of Neurosciences, University of California San Diego, La Jolla, CA, United States
ap Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, United States
aq Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, United States
ar CNR-MAJ, INSERM U614 and Department of Neurology, CHU Charles Nicolle, Rouen, France
as Vanderbilt Center for Human Genetics Research, Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, United States
at The John P. Hussman Institute for Human Genomics, University of Miami, Miami, FL, United States
au Dr John T. Macdonald Foundation Department of Human Genetics, University of Miami, Miami, FL, United States
av Department of Biostatistics, Boston University, Boston, MA, United States
aw Department of Medicine (Genetics Program), Boston University, Boston, MA, United States
ax Department of Ophthalmology, Boston University, Boston, MA, United States
ay Department of Neurology, Boston University, Boston, MA, United States
az Department of Epidemiology, Boston University, Boston, MA, United States
ba Department of Neurology, University of California Los Angeles, Los Angeles, CA, United States
bb Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, United States
bc Department of Medicine (Genetics Program), Boston University, Boston, MA, United States
bd Department of Pharmacology and Neuroscience, University of Texas Southwestern, Fort Worth, TX, United States
be Department of Human Genetics, University of Pittsburgh, Pittsburgh, PA, United States
bf Civin Laboratory for Neuropathology, Banner Sun Health Research Institute, Phoenix, AZ, United States
bg The John P. Hussman Institute for Human Genomics, University of Miami, Miami, FL, United States
bh Dr. John T. Macdonald Foundation Department of Human Genetics, University of Miami, Miami, FL, United States
bi National Alzheimer's Coordinating Center, University of Washington, Seattle, WA, United States
bj Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, United States
bk Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, United States
bl Department of Pathology, Northwestern University, Chicago, IL, United States
bm Department of Neurology, University of Washington, Seattle, WA, United States
bn Department of Epidemiology, Harvard School of Public Health, Boston, MA, United States
bo Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States
bp Department of Neurology, Mayo Clinic, Rochester, MN, United States
bq Swedish Medical Center, Seattle, WA, United States
br Department of Neurology, University of California San Francisco, San Francisco, CA, United States
bs Department of Medicine, Duke University, Durham, NC, United States
bt Department of Neuroscience, Mount Sinai School of Medicine, New York, NY, United States
bu Department of Psychiatry, Mount Sinai School of Medicine, New York, NY, United States
bv Departments of Genetics and Genomic Sciences, Mount Sinai School of Medicine, New York, NY, United States
bw Department of Pathology and Immunology, Washington University, St Louis, MO, United States
bx Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, United States
by Byrd Alzheimer Institute, University of Southern Florida Health, Tampa, FL, United States
bz Fred Hutchinson Cancer Research Center, Seattle, WA, United States
ca Department of Psychiatry, Vanderbilt University, Nashville, TN, United States
cb Department of Neuroscience, Mayo Clinic, Jacksonville, FL, United States
cc Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, United States
cd Department of Neurology, University of Southern California, Los Angeles, CA, United States
ce Department of Neurology, University of Alabama at Birmingham, Birmingham, AL, United States
cf Neurogenomics Division, Translational Genomics Research Institute, Phoenix, AZ, United States
cg Institute for Memory Impairments and Neurological Disorders, University of California Irvine, Irvine, CA, United States
ch Department of Medicine, University of Washington, Seattle, WA, United States
ci Department of Psychiatry, Hope Center Program on Protein Aggregation and Neurodegeneration, Washington University School of Medicine, St Louis, MO, United States
cj Program in Translational NeuroPsychiatric Genomics, Department of Neurology, Brigham and Women's Hospital, Boston, MA, United States
ck Program in Medical and Population Genetics, Broad Institute, Cambridge, MA, United States
cl Department of Neurology, University of California Davis, Sacramento, CA, United States
cm University of Virginia School of Medicine, Charlottesville, VA, United States
cn Department of Neurology, University of Texas Southwestern, Dallas, TX, United States
co Wien Center for Alzheimer's Disease and Memory Disorders, Mount Sinai Medical Center, Miami Beach, FL, United States
cp Department of Pathology and Laboratory Medicine, University of California Davis, Sacramento, CA, United States
cq Department of Neurology, Mayo Clinic, Jacksonville, FL, United States
cr Rush Institute for Healthy Aging, Department of Internal Medicine, Rush University Medical Center, Chicago, IL, United States
cs Department of Medical and Molecular Genetics, Indiana University, Indianapolis, IN, United States
ct Department of Neurology, Indiana University, Indianapolis, IN, United States
cu Department of Psychiatry, New York University, New York, NY, United States
cv C.S. Kubik Laboratory for Neuropathology, Massachusetts General Hospital, Charlestown, MA, United States
cw Department of Neurosciences, University of California San Diego, La Jolla, CA, United States
cx Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, United States
cy Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA, United States
cz Emory Alzheimer's Disease Center, Emory University, Atlanta, GA, United States
da Neurogenetics Program, University of California Los Angeles, Los Angeles, CA, United States
db Department of Pathology and Laboratory Medicine, Indiana University, Indianapolis, IN, United States
dc Department of Neurology, University of Michigan, Ann Arbor, MI, United States
dd Department of Psychiatry, University of Michigan, Ann Arbor, MI, United States
de Department of Neurology, Emory University, Atlanta, GA, United States
df Department of Neurology, Boston University, Boston, MA, United States
dg Department of Epidemiology, Boston University, Boston, MA, United States
dh Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States
di Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, PA, United States
dj Department of Pathology (Neuropathology), University of Pittsburgh, Pittsburgh, PA, United States
dk Institute of Neurology, University College London, Queen Square, London, United Kingdom
dl Department of Molecular and Biomedical Pharmacology, University of California Irvine, Irvine, CA, United States
dm Taub Institute on Alzheimer's Disease and the Aging Brain, Department of Neurology, Columbia University, New York, NY, United States
dn Department of Pathology, Duke University, Durham, NC, United States
do Department of Genome Sciences, University of Washington, Seattle, WA, United States
dp Department of Medicine (Medical Genetics), University of Washington, Seattle, WA, United States
dq Department of Neurology, University of Kentucky, Lexington, KY, United States
dr Department of Psychiatry and Behavioral Sciences, Northwestern University, Chicago, IL, United States
ds Department of Biostatistics, Boston University, Boston, MA, United States
dt Department of Ophthalmology, Boston University, Boston, MA, United States
du University of Pittsburgh Alheimer's Disease Research Center, Pittsburgh, PA, United States
dv Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, United States
dw Department of Biology, Brigham Young University, Provo, UT, United States
dx Department of Neurology, Oregon Health and Science University, Portland, OR, United States
dy Department of Biomedical Engineering, Oregon Health and Science University, Portland, OR, United States
dz Department of Pathology and Laboratory Medicine, University of California Irvine, Irvine, CA, United States
ea Department of Pathology, Boston University, Boston, MA, United States
eb Department of Molecular and Medical Genetics, Oregon Health and Science University, Portland, OR, United States
ec Department of Epidemiology, University of Washington, Seattle, WA, United States
ed Group Health Research Institute, Seattle, WA, United States
ee Department of Pathology, University of Michigan, Ann Arbor, MI, United States
ef Department of Preventive Medicine, University of Southern California, Los Angeles, CA, United States
eg Department of Medicine - Pulmonary, New York University, New York, NY, United States
eh Department of Neurology, University of Miami, Miami, FL, United States
ei Department of Pathology, University of California San Diego, La Jolla, CA, United States
ej School of Nursing Northwest Research Group on Aging, University of Washington, Seattle, WA, United States
ek Alzheimer's Disease Center, Northwestern University, Chicago, IL, United States
el Cognitive Neurology, Northwestern University, Chicago, IL, United States
em Department of Pathology, University of Southern California, Los Angeles, CA, United States
en Department of Pathology, University of Washington, Seattle, WA, United States
eo Department of Neurology, Washington University, St Louis, MO, United States
ep Department of Psychiatry and Behavioral Sciences, University of Miami, Miami, FL, United States
eq Department of Anatomic Pathology, Mayo Clinic, Rochester, MN, United States
er Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, United States
es Department of Pathology, Mount Sinai School of Medicine, New York, NY, United States
et Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA, United States
eu Department of Psychiatry, University of Arizona, Phoenix, AZ, United States
ev Arizona Alzheimer's Consortium, Phoenix, AZ, United States
ew Banner Alzheimer's Institute, Phoenix, AZ, United States
ex Alzheimer's Disease Center, New York University, New York, NY, United States
ey Taub Institute on Alzheimer's Disease and the Aging Brain, Columbia University, New York, NY, United States
ez Taub Institute on Alzheimer's Disease and the Aging Brain, Department of Pathology, Columbia University, New York, NY, United States
fa Gertrude H. Sergievsky Center, Columbia University, New York, NY, United States
fb Department of Neurology, Columbia University, New York, NY, United States
fc Tanz Centre for Research in Neurodegenerative Disease, University of Toronto, Toronto, ON, Canada
fd Department of Radiology and Imaging Sciences, Indiana University, Indianapolis, IN, United States
fe Department of Pathology (Neuropathology), Rush University Medical Center, Chicago, IL, United States
ff Department of Psychiatry, University of Southern California, Los Angeles, CA, United States
fg Department of Pathology, Columbia University, New York, NY, United States
fh Cambridge Institute for Medical Research, Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom
fi Department of Pathology, Johns Hopkins University, Baltimore, MD, United States
fj Department of Pathology and Laboratory Medicine, University of California Los Angeles, Los Angeles, CA, United States
fk Department of Psychiatry and Behavioral Sciences, Duke University, Durham, NC, United States
fl Department of Pathology, Oregon Health and Science University, Portland, OR, United States

Abstract
Rare mutations in the gene encoding for tau (MAPT, microtubule-associated protein tau) cause frontotemporal dementia-spectrum (FTD-s) disorders, including FTD, progressive supranuclear palsy (PSP) and corticobasal syndrome, and a common extended haplotype spanning across the MAPT locus is associated with increased risk of PSP and Parkinson's disease. We identified a rare tau variant (p.A152T) in a patient with a clinical diagnosis of PSP and assessed its frequency in multiple independent series of patients with neurodegenerative conditions and controls, in a total of 15 369 subjects. Tau p.A152T significantly increases the risk for both FTD-s (n = 2139, OR = 3.0, CI: 1.6-5.6, P = 0.0005) and Alzheimer's disease (AD) (n = 3345, OR = 2.3, CI: 1.3-4.2, P = 0.004) compared with 9047 controls. Functionally, p.A152T (i) decreases the binding of tau to microtubules and therefore promotes microtubule assembly less efficiently; and (ii) reduces the tendency to form abnormal fibers. However, there is a pronounced increase in the formation of tau oligomers. Importantly, these findings suggest that other regions of the tau protein may be crucial in regulating normal function, as the p.A152 residue is distal to the domains considered responsible for microtubule interactions or aggregation. These data provide both the first genetic evidence and functional studies supporting the role of MAPT p.A152T as a rare risk factor for both FTD-s and AD and the concept that rare variants can increase the risk for relatively common, complex neurodegenerative diseases, but since no clear significance threshold for rare genetic variation has been established, some caution is warranted until the findings are further replicated. © The Author 2012. Published by Oxford University Press. All rights reserved.

Document Type: Article
Source: Scopus

 

Chiang, C.D., Lewis, C.L., Wright, M.D.E., Agapova, S., Akers, B., Azad, T.D., Banerjee, K., Carrera, P., Chen, A., Chen, J., Chi, X., Chiou, J., Cooper, J., Czurylo, M., Downs, C., Ebstein, S.Y., Fahey, P.G., Goldman, J.W., Grieff, A., Hsiung, S., Hu, R., Huang, Y., Kapuria, A., Li, K., Marcu, I., Moore, S.H., Moseley, A.C., Nauman, N., Ness, K.M., Ngai, D.M., Panzer, A., Peters, P., Qin, E.Y., Sadhu, S., Sariol, A., Schellhase, A., Schoer, M.B., Steinberg, M., Surick, G., Tsai, C.A., Underwood, K., Wang, A., Wang, M.H., Wang, V.M., Westrich, D., Yockey, L.J., Zhang, L., Herzog, E.D.
Learning chronobiology by improving wikipedia
(2012) Journal of Biological Rhythms, 27 (4), pp. 333-336. 

Department of Biology, Washington University, Box 1137, St. Louis, MO 63130, United States

Abstract
Although chronobiology is of growing interest to scientists, physicians, and the general public, access to recent discoveries and historical perspectives is limited. Wikipedia is an online, user-written encyclopedia that could enhance public access to current understanding in chronobiology. However, Wikipedia is lacking important information and is not universally trusted. Here, 46 students in a university course edited Wikipedia to enhance public access to important discoveries in chronobiology. Students worked for an average of 9 h each to evaluate the primary literature and available Wikipedia information, nominated sites for editing, and, after voting, edited the 15 Wikipedia pages they determined to be highest priorities. This assignment (http://www.nslc. wustl.edu/courses/Bio4030/wikipedia-project.html) was easy to implement, required relatively short time commitments from the professor and students, and had measurable impacts on Wikipedia and the students. Students created 3 new Wikipedia sites, edited 12 additional sites, and cited 347 peer-reviewed articles. The targeted sites all became top hits in online search engines. Because their writing was and will be read by a worldwide audience, students found the experience rewarding. Students reported significantly increased comfort with reading, critiquing, and summarizing primary literature and benefited from seeing their work edited by other scientists and editors of Wikipedia. We conclude that, in a short project, students can assist in making chronobiology widely accessible and learn from the editorial process. © 2012 The Author(s).

Author Keywords
circadian;  Clock gene;  Period gene;  Timeless gene;  undergraduate education

Document Type: Article
Source: Scopus

 

McClelland, C.a , Van Stavern, G.P.a b , Shepherd, J.B.a , Gordon, M.a , Huecker, J.a
Neuroimaging in patients referred to a neuro-ophthalmology service: The rates of appropriateness and concordance in interpretation
(2012) Ophthalmology, 119 (8), pp. 1701-1704. 

a Department of Ophthalmology and Visual Sciences, Washington University, 660 S. Euclid Ave., St. Louis, MO 63110, United States
b Department of Neurology, Washington University, St. Louis, MO, United States

Abstract
Objective: Neuroimaging studies frequently are ordered to investigate neuro-ophthalmic symptoms. When misused, these studies are expensive and time consuming. This study describes the type and frequency of neuroimaging errors in patients referred to an academic neuro-ophthalmology service and measures how frequently these neuroimaging studies were reinterpreted. Design: Prospective cohort study. Participants: Eighty-four consecutive patients referred to an academic neuro-ophthalmology practice. Methods: From November 2009 through July 2010, 84 consecutive new patients who had undergone a neuroimaging study in the last 12 months specifically to evaluate their presenting neuro-ophthalmic symptoms were enrolled prospectively. Participants then underwent a complete neuro-ophthalmic evaluation, followed by a review of prior neuroimaging. Questions regarding appropriateness of the most recent imaging, concordance of radiologic interpretation, and re-evaluation of referring diagnoses were answered by the attending physician. Main Outcome Measures: The frequency and types of errors committed in the use of neuroimaging and the frequency of reinterpretation of prereferral neuroimaging studies after neuro-ophthalmic history and examination. Results: Most study participants (84.5%; 71/84) underwent magnetic resonance imaging before referral; 15.5% (13/84) underwent only computed tomography. The rate of suboptimal neuroimaging studies was 38.1% (32/84). The 3 most common reasons for suboptimal studies were incomplete area of imaging (34.4%; 11/32), wrong study type (28.1%; 9/32), and poor image quality (21.9%; 7/32). Twenty-four of 84 subjects (28.6%) required additional neuroimaging. The authors agreed with the radiology interpretation of the prior neuroimaging studies in most patients (77.4%; 65/84). The most common anatomic locations for discordance in interpretation were the intraorbital optic nerve (35%; 7/20) and the brainstem (20%; 4/20). Conclusions: There was a high rate of suboptimal neuroimaging studies performed in patients referred for neuro-ophthalmology examination. These findings have significant implications given the increasing attention to resource use currently and in the near future. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article. © 2012 American Academy of Ophthalmology.

Document Type: Conference Paper
Source: Scopus

 

Racette, B.A.a , Aschner, M.b , Guilarte, T.R.c , Dydak, U.d , Criswell, S.R.a , Zheng, W.d
Pathophysiology of manganese-associated neurotoxicity
(2012) NeuroToxicology, 33 (4), pp. 881-886. 

a Department of Neurology, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63131, United States
b Departments of Pediatrics, Pharmacology, The Kennedy Center for Research on Human Development, Vanderbilt University Medical Center, 110 Magnolia Circle, Nashville, TN 37203, United States
c Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, 722 W. 168th St., New York, NY 10032, United States
d School of Health Sciences, Purdue University, 550 Stadium Mall Dr., West Lafayette, IN 47907, United States

Abstract
Manganese (Mn) is a well established neurotoxin associated with specific damage to the basal ganglia in humans. The phenotype associated with Mn neurotoxicity was first described in two workers with occupational exposure to Mn oxide (Couper, 1837). Although the description did not use modern clinical terminology, a parkinsonian illness characterized by slowness of movement (bradykinesia), masked facies, and gait impairment (postural instability) appears to have predominated. Nearly 100 years later an outbreak of an atypical parkinsonian illness in a Chilean Mn mine provided a phenotypic description of a fulminant neurologic disorder with parkinsonism, dystonia, and neuropsychiatric symptoms (Rodier, 1955). Exposures associated with this syndrome were massive and an order of magnitude greater than modern exposures (Rodier, 1955; Hobson et al., 2011). The clinical syndrome associated with Mn neurotoxicity has been called manganism.Modern exposures to Mn occur primarily through occupations in the steel industry and welding. These exposures are often chronic and varied, occurring over decades in the healthy workforce. Although the severe neurologic disorder described by Rodier and Couper are no longer seen, several reports have suggested a possible increased risk of neurotoxicity in these workers (Racette et al., 2005b; Bowler et al., 2007; Harris et al., 2011). Based upon limited prior imaging and pathologic investigations into the pathophysiology of neurotoxicity in Mn exposed workers (Huang et al., 2003), many investigators have concluded that the syndrome spares the dopamine system distinguishing manganism from Parkinson disease (PD), the most common cause of parkinsonism in the general population, and a disease with characteristic degenerative changes in the dopaminergic system (Jankovic, 2005).The purpose of this symposium was to highlight recent advances in the understanding of the pathophysiology of Mn associated neurotoxicity from Caenorhabditis elegans to humans. Dr. Aschner's presentation discussed mechanisms of dopaminergic neuronal toxicity in C. elegans and demonstrates a compelling potential role of Mn in dopaminergic degeneration. Dr. Guilarte's experimental, non-human primate model of Mn neurotoxicity suggests that Mn decreases dopamine release in the brain without loss of neuronal integrity markers, including dopamine. Dr. Racette's presentation demonstrates a unique pattern of dopaminergic dysfunction in active welders with chronic exposure to Mn containing welding fumes. Finally, Dr. Dydak presented novel magnetic resonance (MR) spectroscopy data in Mn exposed smelter workers and demonstrated abnormalities in the thalamus and frontal cortex for those workers. This symposium provided some converging evidence of the potential neurotoxic impact of Mn on the dopaminergic system and challenged existing paradigms on the pathophysiology of Mn in the central nervous system. © 2011 Elsevier Inc.

Author Keywords
Manganese;  MRI;  Parkinsonism;  PET

Document Type: Article
Source: Scopus

 

Powers, A.D., Oltmanns, T.F.
Personality disorders and physical health: A longitudinal examination of physical functioning, healthcare utilization, and health-related behaviors in middle-aged adults
(2012) Journal of Personality Disorders, 26 (4), pp. 524-538. 

Washington University, Department of Psychology, 1 Brookings Drive, Campus Box 1125, St. Louis, MO 63130, United States

Abstract
Personality disorders (PDs) have significant, long-term effects in many areas, including physical health outcomes such as increased risk for chronic disease and mortality. Although research has documented this detrimental impact in relation to long-term physical health, no one has explored the more immediate influence of disordered personality on aspects of physical functioning, such as pain level, or health-related behaviors, such as medication use. The present study examined the unique effects of PD features on physical functioning, medical resource utilization, and prescription medication use to determine potential risk associated with PDs. We studied an epidemiologically-based sample (N = 608) of Saint Louis residents (ages 55-64) over two time points (6 months apart). We found that disordered personality was significantly predictive of worse physical functioning, role limitations, fatigue, and pain at both time points, even when current health problems, the presence of depression, and health behaviors (i.e., smoking, drinking, exercise) were controlled. PD features were also predictive of increased healthcare utilization and medication use at follow-up. These results suggest that the presence of disordered personality may be an important risk factor for worse functioning, regardless of actual health status. © 2012 The Guilford Press.

Document Type: Article
Source: Scopus

 

Wig, G.S.
Repetition suppression and repetition priming are processing outcomes
(2012) Cognitive Neuroscience, 3 (3-4), pp. 247-248. 

Department of Neurology, Washington University School of Medicine, St Louis, United States

Abstract
There is considerable evidence that repetition suppression (RS) is a cortical signature of previous exposure to the environment. In many instances RS in specific brain regions is accompanied by improvements in specific behavioral measures; both observations are outcomes of repeated processing. In understanding the mechanism by which brain changes give rise to behavioral changes, it is important to consider what aspect of the environment a given brain area or set of areas processes, and how this might be expressed behaviorally. © 2012 Copyright 2012 Psychology Press, an imprint of the Taylor & Francis Group, an Informa business.

Document Type: Editorial
Source: Scopus

 

Nelson, G.a b , Criswell, S.R.c , Zhang, J.d , Murray, J.a b , Racette, B.A.c
Research capacity development in South African manganese mines to bridge exposure and neuropathologic outcomes
(2012) NeuroToxicology, 33 (4), pp. 683-686. 

a National Institute for Occupational Health, National Health Laboratory Service, PO Box 4788, Johannesburg 2000, South Africa
b School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, 7 York Road, Parktown 2193, South Africa
c Washington University School of Medicine, 660 South Euclid Ave, Box 8111, St. Louis, MO 63131, United States
d University of Washington School of Medicine, UW Harborview Medical Center, R and T Building, 300 Ninth Ave, Box 359635, Seattle, WA 98104, United States

Abstract
Manganese (Mn) is a common occupational exposure worldwide. Recent studies indicate clinical and imaging evidence of neurotoxicity in chronically exposed workers. The pathologic significance of these findings is unclear. South Africa produces over 80% of the world's Mn from mines from a desert region in the Northern Cape Province. An autopsy program at the National Institute for Occupational Health (NIOH) in South Africa has provided compensation to families for mining-related lung diseases for almost 100 years. Building on this, we implemented a brain autopsy program to investigate the feasibility of obtaining brains from South African Mn miners and non-exposed reference miners to investigate neuropathologic consequences of chronic Mn exposure. Employing an experienced occupational health nurse, we identified deceased miners within 100 square km of the Mn mines. The nurse was notified of any Mn (case) or other (reference) miner or ex-miner death by local medical practitioners, occupational health and mine physicians, and community members, and families were approached for consent to remove the brains in addition to the cardio-respiratory organs. Families of deceased miners who had an autopsy at the NIOH in Johannesburg were also approached. To confirm exposure in Mn miners, mean pallidal indices were compared between Mn miners and non-exposed reference miners. Sixty-eight potential brain donors were identified; we obtained consent from the families to remove 51 (75%). The mean autopsy interval was seven days. With optimized fixation methods, the tissue quality of the brains for gross and regular microscopic examination was excellent. Ex vivo MRI demonstrated increased pallidal index in Mn miners compared to reference miners. We conclude that obtaining brain tissue from deceased miners in South Africa is highly successful with only a modest investment in local infrastructure. Tissue quality was excellent and should be ideal to investigate the neuropathologic consequences of chronic occupational Mn exposure. © 2012 Elsevier Inc.

Author Keywords
Manganese;  MRI;  Neuropathology;  Parkinsonism

Document Type: Article
Source: Scopus

 

Mall, N.A.a , Buchowski, J.b , Zebala, L.b , Brophy, R.H.b , Wright, R.W.b , Matava, M.J.b c
Spine and axial skeleton injuries in the national football league
(2012) American Journal of Sports Medicine, 40 (8), pp. 1755-1761. 

a Division of Sports Medicine, Department of Orthopaedic Surgery, Rush University Medical Center, Chicago, IL, United States
b Washington University School of Medicine, Department of Orthopedics, Division of Spinal Surgery, 14532 South Outer Forty Drive, Chesterfield, MO 63017, United States
c Division of Sports Medicine, Department of Orthopedics, Washington University School of Medicine, Chesterfield, MO, United States

Abstract
Background: The majority of previous literature focusing on spinal injuries in American football players is centered around catastrophic injuries; however, this may underestimate the true number of these injuries in this athletic cohort. Purpose: The goals of this study were to (1) report the incidence of spinal and axial skeleton injuries, both minor and severe, in the National Football League (NFL) over an 11-year period; (2) determine the incidence of spinal injury by injury type, anatomic location, player position, mechanism of injury, and type of exposure (practice vs game); and (3) determine the average number of practices and days missed because of injury for each injury type. Study Design: Descriptive epidemiological study. Methods: All documented injuries to the cervical, thoracic, and lumbar spine; pelvis; ribs; and spinal cord were retrospectively analyzed using the NFLs injury surveillance database over a period of 11 seasons from 2000 through 2010. The data were analyzed by the number of injuries per athlete-exposure, the anatomic location and type of injury, player position, mechanism of injury, and number of days missed per injury. Results: A total of 2208 injuries occurred to the spine or axial skeleton over an 11-season interval in the NFL, with a mean loss of 25.7 days per injury. This represented 7%of the total injuries during this time period. Of these 2208 injuries, 987 (44.7%) occurred in the cervical spine. Time missed from play was greatest for thoracic disc herniations (189 days/injury). Other injuries that had a mean time missed greater than 30 days included (in descending order) cervical fracture (120 days/injury), cervical disc degeneration/herniation (85 days/injury), spinal cord injury (77 days/injury), lumbar disc degeneration/herniation (52 days/injury), thoracic fracture (34 days/injury), and thoracic nerve injury (30 days/injury). Offensive linemen were the most likely to suffer a spinal injury, followed by defensive backs, defensive linemen, and linebackers. Blocking and tackling were the 2 most frequent injury mechanisms reported. Conclusion: Spinal and axial skeleton injuries occur frequently in the NFL and can result in significant time missed from practices and games. Tackling and blocking result in the greatest number of injuries, and players performing these activities are the most likely to sustain a spinal injury. The results of this study may be used as an impetus to formulate strategies to prevent spinal injuries in American football players. © 2012 The Author(s).

Author Keywords
axial skeleton;  NFL;  professional football;  spinal cord injury;  spine

Document Type: Article
Source: Scopus

 

Adler, J.M.a , Chin, E.D.a , Kolisetty, A.P.a , Oltmanns, T.F.b
The distinguishing characteristics of narrative identity in adults with features of Borderline Personality Disorder: An empirical investigation
(2012) Journal of Personality Disorders, 26 (4), pp. 498-512. 

a Franklin W. Olin College of Engineering, Milas Hall 368, Olin Way, Needham, MA 02446, United States
b Washington University in Saint Louis, United States

Abstract
While identity disturbance has long been considered one of the defining features of Borderline Personality Disorder (BPD), the present study marks only the third empirical investigation to assess it and the first to do so from the perspective of research on narrative identity. Drawing on the rich tradition of studying narrative identity, the present study examined identity disturbance in a group of 40 mid-life adults, 20 with features of BPD and a matched sample of 20 without BPD. Extensive life story interviews were analyzed for a variety of narrative elements and the themes of agency, communion fulfillment (but not communion), and narrative coherence significantly distinguished the stories of those people with features of BPD from those without the disorder. In addition, associations between the theme of agency and psychopathology were evident six and twelve months following the life story interview. This study seeks to bridge the mutually-informative fields of research on personality disorders and normal identity processes. © 2012 The Guilford Press.

Document Type: Article
Source: Scopus

 
Kidokoro, H.a , Inder, T.a , Okumura, A.b , Watanabe, K.c
What does cyclicity on amplitude-integrated EEG mean
(2012) Journal of Perinatology, 32 (8), pp. 565-569. 

a Department of Pediatrics, Washington University in St Louis, 660 South Euclid Ave, St Louis, MO 63110, United States
b Department of Pediatrics, Juntendo University School of Medicine, Tokyo, Japan
c Faculty of Health and Medical Science, Aichi Shukutoku University, Nagoya, Japan

Abstract
In the context of amplitude-integrated electroencephalography (aEEG), the term sleep-wake cycling (SWC), which is frequently used by clinicians and researchers, should be changed to cyclicity. SWC is a technical term that refers to the biological pattern of alternating sleeping and waking states, which is difficult to define with only aEEG and no physical parameters. Additionally, the absence of cyclicity on aEEG is a more robust reflection of the sequence of the suppressed background patterns of an aEEG following cerebral injury or dysfunction than are sleep/wake states. © 2012 Nature America, Inc. All rights reserved.

Author Keywords
conventional EEG;  neonates;  sleep-wake cycling

Document Type: Article
Source: Scopus

 

Patel, A.a , Harker, N.a , Moreira-Santos, L.b , Ferreira, M.b , Alden, K.c d , Timmis, J.d , Foster, K.a , Garefalaki, A.a , Pachnis, P.a , Andrews, P.d , Enomoto, H.e , Milbrandt, J.f , Pachnis, V.g , Coles, M.C.c , Kioussis, D.a , Veiga-Fernandes, H.b
Differential RET signaling pathways drive development of the enteric lymphoid and nervous systems
(2012) Science Signaling, 5 (235), art. no. ra55, . 

a Division of Molecular Immunology, MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, United Kingdom
b Instituto de Medicina Molecular, Faculdade de Medicina de Lisboa, Edifício Egas Moniz, Av. Prof. Egas Moniz, 1649-028 Lisboa, Portugal
c Department of Biology, Hull York Medical School, University of York, York YO10 5DD, United Kingdom
d Departments of Computer Science and Electronics, University of York, York YO10 5DD, United Kingdom
e Laboratory for Neuronal Differentiation and Regeneration, RIKEN Center for Developmental Biology, Kobe 650-0047, Japan
f Hope Centre for Neurological Disorders, Genetics Department, Washington University School of Medicine, St. Louis, MO 63110, United States
g Division of Molecular Neurobiology, MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, United Kingdom

Abstract
During the early development of the gastrointestinal tract, signaling through the receptor tyrosine kinase RET is required for initiation of lymphoid organ (Peyer's patch) formation and for intestinal innervation by enteric neurons. RET signaling occurs through glial cell line-derived neurotrophic factor (GDNF) family receptor a co-receptors present in the same cell (signaling in cis). It is unclear whether RET signaling in trans, which occurs in vitro through co-receptors from other cells, has a biological role. We showed that the initial aggregation of hematopoietic cells to form lymphoid clusters occurred in a RET-dependent, chemokine-independent manner through adhesion-mediated arrest of lymphoid tissue initiator (LTin) cells. Lymphoid tissue inducer cells were not necessary for this initiation phase. LTin cells responded to all RET ligands in trans, requiring factors from other cells, whereas RET was activated in enteric neurons exclusively by GDNF in cis. Furthermore, genetic and molecular approaches revealed that the versatile RET responses in LTin cells were determined by distinct patterns of expression of the genes encoding RET and its co-receptors. Our study shows that a trans RET response in LTin cells determines the initial phase of enteric lymphoid organ morphogenesis, and suggests that differential co-expression of Ret and Gfra can control the specificity of RET signaling.

Document Type: Article
Source: Scopus

 

Ciliberto, M.A., Weisenberg, J.L.Z., Wong, M.
Clinical utility, safety, and tolerability of ezogabine (retigabine) in the treatment of epilepsy
(2012) Drug, Healthcare and Patient Safety, 4 (1), pp. 81-86. 

Department of Neurology, Washington University School of Medicine, Campus Box 8111, 660 S Euclid Avenue, St Louis, MO 63110, United States

Abstract
One-third of patients with epilepsy continue to have seizures despite current treatments, indicating the need for better antiseizure medications with novel mechanisms of action. Ezogabine (retigabine) has recently been approved for adjunctive treatment of partial-onset seizures in adult patients with epilepsy. Ezogabine utilizes a novel mechanism of action, involving activation of specific potassium channels. The most common side effects of ezogabine are shared by most antiseizure medications and primarily consist of central nervous system (CNS) symptoms, such as somnolence, dizziness, confusion, and fatigue. In addition, a small percentage of patients on ezogabine experience a unique adverse effect affecting the bladder, which results in urinary hesitancy; thus, patients on ezogabine should be monitored carefully for potential urological symptoms. Overall, ezogabine appears to be well tolerated and represents a reasonable new option for treating patients with intractable epilepsy. © 2012 Ciliberto et al.

Author Keywords
Antiepileptic drug;  Bladder;  Potassium channels;  Seizure

Document Type: Review
Source: Scopus

 

Derringer, J.a , Krueger, R.F.b , Dick, D.M.c , Aliev, F.c d , Grucza, R.A.e , Saccone, S.e , Agrawal, A.e , Edenberg, H.J.f , Goate, A.M.e , Hesselbrock, V.M.g , Kramer, J.R.h , Lin, P.e , Neuman, R.J.e , Nurnberger Jr., J.I.f , Rice, J.P.e , Tischfield, J.A.i , Bierut, L.J.e
The aggregate effect of dopamine genes on dependence symptoms among cocaine users: Cross-validation of a candidate system scoring approach
(2012) Behavior Genetics, 42 (4), pp. 626-635. 

a Institute for Behavioral Genetics, University of Colorado Boulder, Boulder, CO 80309-0447, United States
b University of Minnesota, Minneapolis, United States
c Virginia Commonwealth University, Richmond, United States
d Ankara University, Ankara, Turkey
e Washington University in St. Louis, St. Louis, United States
f Indiana University, Bloomington, United States
g University of Connecticut, Farmington, United States
h University of Iowa, Iowa City, United States
i Rutgers University, Piscataway, United States

Abstract
Genome-wide studies of psychiatric conditions frequently fail to explain a substantial proportion of variance, and replication of individual SNP effects is rare. We demonstrate a selective scoring approach, in which variants from several genes known to directly affect the dopamine system are considered concurrently to explain individual differences in cocaine dependence symptoms. 273 SNPs from eight dopamine-related genes were tested for association with cocaine dependence symptoms in an initial training sample. We identified a four-SNP score that accounted for 0.55% of the variance in a separate testing sample (p = 0.037). These findings suggest that (1) limiting investigated SNPs to those located in genes of theoretical importance improves the chances of identifying replicable effects by reducing statistical penalties for multiple testing, and (2) considering top-associated SNPs in the aggregate can reveal replicable effects that are too small to be identified at the level of individual SNPs. © Springer Science+Business Media, LLC 2012.

Author Keywords
Candidate gene;  Cocaine dependence;  Dopamine

Document Type: Article
Source: Scopus

 

Qian, C.a , Al-Aidroos, N.a , West, G.a , Abrams, R.A.b , Pratt, J.a
The visual P2 is attenuated for attended objects near the hands
(2012) Cognitive Neuroscience, 3 (2), pp. 98-104. 

a Department of Psychology, University of Toronto, 100 St. George Street, Toronto, ON M5S 3G3, Canada
b Department of Psychology, Washington University, St. Louis, MO, United States

Abstract
Vision is altered when people place their hands near the object they are observing. To investigate the neural processes underlying this effect, we measured electroencephalographic visual-evoked potentials (VEPs) elicited by reversing checkerboards, while participants' hands either surrounded the visual display or rested at their sides. We found the P2 component was attenuated for hand-proximal stimuli, but only when participants attended to the location of the checkerboard. In Experiment 1, participants performed an attention-demanding color-change task that was presented centrally, and the P2 component was attenuated for central, but not peripheral, checkerboards. In Experiment 2, participants performed the attention task in the periphery, and the P2 was attenuated for peripheral, but not central, checkerboards. These results suggest that hand-proximal stimuli benefit from enhanced selective attention at later stages of perceptual processing. The effect only occurs for objects at task-relevant locations, however, even when task-irrelevant locations are physically closer to the hands. © 2012 Copyright 2012 Psychology Press, an imprint of the Taylor & Francis Group, an Informa business.

Author Keywords
Action;  Attention;  VEP

Document Type: Article
Source: Scopus

 

Bisbee, C.C.a , Vickar, G.M.b c d
A review of psychoeducation for Patients with Schizophrenia
(2012) Psychiatric Annals, 42 (6), pp. 205-210. 

a The Wellness Coalition, 3060 Mobile Highway, Montgomery, AL 36108, United States
b STEPS, Christian Hospital NE, St. Louis, MO, United States
c Department of Psychiatry, Washington University, St. Louis, MO, United States
d Department of Psychiatry, St. Matthews University, Cayman Islands

Document Type: Article
Source: Scopus

 

Vickar, G.M.a b c
Evolution of psychoeducation
(2012) Psychiatric Annals, 42 (6), pp. 203-204. 

a Department of Psychiatry, Christian Hospital NE, St. Louis, MO, United States
b Department of Psychiatry, Washington University, St. Louis, MO, United States
c Department of Psychiatry, St. Matthews University, Cayman Islands

Document Type: Editorial
Source: Scopus

 

Repovš, G.a , Barch, D.M.b c d
Working memory related brain network connectivity in individuals with schizophrenia and their siblings
(2012) Frontiers in Human Neuroscience, (JUNE 2012), . 


a Department of Psychology, University of Ljubljana, Askerceva 2, SI-1000 Ljubljana, Slovenia
b Department of Psychology, Washington University in St. Louis, St. Louis, United States
c Department of Psychiatry, Washington University in St. Louis, St. Louis, United States
d Department of Radiology, Washington University in St. Louis, St. Louis, United States

Abstract
A growing number of studies have reported altered functional connectivity in schizophrenia during putatively "task-free" states and during the performance of cognitive tasks. However, there have been few systematic examinations of functional connectivity in schizophrenia across rest and different task states to assess the degree to which altered functional connectivity reflects a stable characteristic or whether connectivity changes vary as a function of task demands. We assessed functional connectivity during rest and during three working memory loads of an N-back task (0-back, 1-back, 2-back) among: (1) individuals with schizophrenia (N = 19); (2) the siblings of individuals with schizophrenia (N = 28); (3) healthy controls (N = 10); and (4) the siblings of healthy controls (N = 17). We examined connectivity within and between four brain networks: (1) frontal-parietal (FP); (2) cingulo-opercular (CO); (3) cerebellar (CER); and (4) default mode (DMN). In terms of within-network connectivity, we found that connectivity within the DMN and FP increased significantly between resting state and 0-back, while connectivity within the CO and CER decreased significantly between resting state and 0-back. Additionally, we found that connectivity within both the DMN and FP was further modulated by memory load. In terms of between network connectivity, we found that the DMN became significantly more "anti-correlated" with the FP, CO, and CER networks during 0-back as compared to rest, and that connectivity between the FP and both CO and CER networks increased with memory load. Individuals with schizophrenia and their siblings showed consistent reductions in connectivity between both the FP and CO networks with the CER network, a finding that was similar in magnitude across rest and all levels of working memory load. These findings are consistent with the hypothesis that altered functional connectivity in schizophrenia reflects a stable characteristic that is present across cognitive states. © 2012 Repovš and Barch.

Author Keywords
Cerebellum;  Cognitive control;  Functional connectivity;  Risk;  Schizophrenia;  Task;  Working memory

Document Type: Article
Source: Scopus

 

Papa, L.a , Lewis, L.M.b , Silvestri, S.a , Falk, J.L.a , Giordano, P.a , Brophy, G.M.d , Demery, J.A.e , Liu, M.C.c , Mo, J.c , Akinyi, L.c , Mondello, S.c , Schmid, K.f , Robertson, C.S.g , Tortella, F.C.f , Hayes, R.L.c , Wang, K.K.W.h
Serum levels of ubiquitin C-terminal hydrolase distinguish mild traumatic brain injury from trauma controls and are elevated in mild and moderate traumatic brain injury patients with intracranial lesions and neurosurgical intervention
(2012) Journal of Trauma and Acute Care Surgery, 72 (5), pp. 1335-1344. 

a Department of Emergency Medicine, Orlando Regional Medical Center, 86 W. Underwood (S-200), Orlando, FL 32806, United States
b Division of Emergency Medicine, Washington University, School of Medicine, St. Louis, MO, United States
c Banyan Biomarkers Inc., Alachua, FL, United States
d Virginia Commonwealth University, Medical College of Virginia Campus, Richmond, VA, United States
e University of Florida Forensic Institute, UF Springhill Health Center, Gainesville, FL, United States
f Division of Psychiatry and Neuroscience, Department of Applied Neurobiology, Walter Reed Army Institute of Research, Silver Spring, MD, United States
g Department of Critical Care and Neurosurgery, Baylor College of Medicine, Houston, TX, United States
h Department of Psychiatry, University of Florida, Gainesville, FL, United States

Abstract
BACKGROUND: This study compared early serum levels of ubiquitin C-terminal hydrolase (UCH-L1) from patients with mild and moderate traumatic brain injury (TBI) with uninjured and injured controls and examined their association with traumatic intracranial lesions on computed tomography (CT) scan (CT positive) and the need for neurosurgical intervention (NSI). METHODS: This prospective cohort study enrolled adult patients presenting to three tertiary care Level I trauma centers after blunt head trauma with loss of consciousness, amnesia, or disorientation and a Glasgow Coma Scale (GCS) score 9 to 15. Control groups included normal uninjured controls and nonhead injured trauma controls presenting to the emergency department with orthopedic injuries or motor vehicle crash without TBI. Blood samples were obtained in all trauma patients within 4 hours of injury and measured by enzyme-linked immunosorbent assay for UCH-L1 (ng/mL ± standard error of the mean). RESULTS: There were 295 patients enrolled, 96 TBI patients (86 with GCS score 13-15 and 10 with GCS score 9-12), and 199 controls (176 uninjured, 16 motor vehicle crash controls, and 7 orthopedic controls). The AUC for distinguishing TBI from uninjured controls was 0.87 (95% confidence interval [CI], 0.82- 0.92) and for distinguishing those TBIs with GCS score 15 from controls was AUC 0.87 (95% CI, 0.81- 0.93). Mean UCH-L1 levels in patients with CT negative versus CT positive were 0.620 (±0.254) and 1.618 (±0.474), respectively (p < 0.001), and the AUC was 0.73 (95% CI, 0.62- 0.84). For patients without and with NSI, levels were 0.627 (0.218) versus 2.568 (0.854; p < 0.001), and the AUC was 0.85 (95% CI, 0.76-0.94). CONCLUSION: UCH-L1 is detectable in serum within an hour of injury and is associated with measures of injury severity including the GCS score, CT lesions, and NSI. Further study is required to validate these findings before clinical application. Copyright © 2012 by Lippincott Williams & Wilkins.

Author Keywords
Biomarkers;  Intracranial lesions;  Neurosurgical intervention;  Serum;  Traumatic brain injury

Document Type: Article
Source: Scopus

 

Fok, S., Schwartz, R., Wronkiewicz, M., Holmes, C., Zhang, J., Somers, T., Bundy, D., Leuthardt, E.
An EEG-based brain computer interface for rehabilitation and restoration of hand control following stroke using ipsilateral cortical physiology.
(2011) Conference proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference, 2011, pp. 6277-6280. 

Biomedical Engineering and Electrical Engineering Department, Washington University in St Louis, MO 63130, USA.

Abstract
The loss of motor control severely impedes activities of daily life. Brain computer interfaces (BCIs) offer new possibilities to treat nervous system injuries, but conventional BCIs use signals from primary motor cortex, the same sites most likely damaged in a stroke causing paralysis. Recent studies found distinct cortical physiology associated with contralesional limb movements in regions distinct from primary motor cortex. To capitalize on these findings, we designed and implemented a BCI that localizes and acquires these brain signals to drive a powered, hand orthotic which opens and closes a patient's hand.

Document Type: Article
Source: Scopus

 

August 8, 2012

Greenberg, J.K.a , Xia, J.b , Zhou, X.b , Thatcher, S.R.c , Gu, X.a , Ament, S.A.d e , Newman, T.C.f , Green, P.J.c , Zhang, W.b g , Robinson, G.E.d f , Ben-Shahar, Y.a
Behavioral plasticity in honey bees is associated with differences in brain microRNA transcriptome
(2012) Genes, Brain and Behavior, 11 (6), pp. 660-670. 


a Department of Biology, Washington University, St. Louis, MO, United States
b Department of Computer Science and Engineering, Washington University, St. Louis, MO, United States
c Delaware Biotechnology Institute, University of Delaware, Newark, DE, United States
d The Neuroscience Program, University of Illinois Urbana-Champaign, Urbana-Champaign, IL, United States
e Institute for Systems Biology, Seattle, WA, United States
f Department of Entomology, University of Illinois Urbana-Champaign, Urbana-Champaign, IL, United States
g Department of Genetics, Washington University School of Medicine, St. Louis, MO, United States

Abstract
Small, non-coding microRNAs (miRNAs) have been implicated in many biological processes, including the development of the nervous system. However, the roles of miRNAs in natural behavioral and neuronal plasticity are not well understood. To help address this we characterized the microRNA transcriptome in the adult worker honey bee head and investigated whether changes in microRNA expression levels in the brain are associated with division of labor among honey bees, a well-established model for socially regulated behavior. We determined that several miRNAs were downregulated in bees that specialize on brood care (nurses) relative to foragers. Additional experiments showed that this downregulation is dependent upon social context; it only occurred when nurse bees were in colonies that also contained foragers. Analyses of conservation patterns of brain-expressed miRNAs across Hymenoptera suggest a role for certain miRNAs in the evolution of the Aculeata, which includes all the eusocial hymenopteran species. Our results support the intriguing hypothesis that miRNAs are important regulators of social behavior at both developmental and evolutionary time scales. © 2012 Blackwell Publishing Ltd and International Behavioural and Neural Genetics Society.


Author Keywords
Division of labor;  Honey bee;  MicroRNA;  Phylogenetics;  Social behavior


Document Type: Article
Source: Scopus

 

Barch, D.M.a b , D'Angelo, G.c , Pieper, C.d , Wilkins, C.H.b , Welsh-Bohmer, K.d , Taylor, W.d , Garcia, K.S.b , Gersing, K.d , Doraiswamy, P.M.d , Sheline, Y.I.b
Cognitive improvement following treatment in late-life depression: Relationship to vascular risk and age of onset
(2012) American Journal of Geriatric Psychiatry, 20 (8), pp. 682-690. 


a Department of Psychology, Washington University, School of Medicine, One Brookings Dr, St. Louis, MO 63130, United States
b Department of Psychiatry, Washington University, School of Medicine, St. Louis, MO, United States
c Department of Radiology, Division of Biostatistics, Washington University School of Medicine, St. Louis, MO, United States
d Department of Psychiatry, Duke University, School of Medicine, Durham, NC, United States

Abstract
OBJECTIVES: To test the hypothesis that the degree of vascular burden and/or age of onset may influence the degree to which cognition can improve during the course of treatment in late-life depression. DESIGN: Measurement of cognition both before and following 12 weeks of treatment with sertraline. SETTING: University medical centers (Washington University and Duke University). PARTICIPANTS: One hundred sixty-six individuals with late-life depression. INTERVENTION: Sertraline treatment. MEASUREMENTS: The cognitive tasks were grouped into five domains (language, processing speed, working memory, episodic memory, and executive function). We measured vascular risk using the Framingham Stroke Risk Profile measure. We measured T2-based white matter hyperintensities using the Fazekas criteria. RESULTS: Both episodic memory and executive function demonstrated significant improvement among adults with late-life depression during treatment with sertraline. Importantly, older age, higher vascular risk scores, and lower baseline Mini-Mental State Examination scores predicted less change in working memory. Furthermore, older age, later age of onset, and higher vascular risk scores predicted less change in executive function. CONCLUSIONS: These results have important clinical implications in that they suggest that a regular assessment of vascular risk in older adults with depression is necessary as a component of treatment planning and in predicting prognosis, both for the course of the depression itself and for the cognitive impairments that often accompany depression in later life. © 2012 American Association for Geriatric Psychiatry.


Author Keywords
Cognition;  treatment;  vascular depression;  white matter Received


Document Type: Article
Source: Scopus

 

Olofsen, E.a , Noppers, I.a , Niesters, M.a , Kharasch, E.b , Aarts, L.a , Sarton, E.a , Dahan, A.a
Estimation of the contribution of norketamine to ketamine-induced acute pain relief and neurocognitive impairment in healthy volunteers
(2012) Anesthesiology, 117 (2), pp. 353-364. 


a Department of Anesthesiology, Leiden University, Medical Center, P5-Q, PO Box 9600, 2300 RC Leiden, Netherlands
b Department of Anesthesiology, Washington University in St. Louis, St. Louis, MI, United States

Abstract
BACKGROUND: The N-methyl-D-aspartate receptor antagonist ketamine is metabolized in the liver into its active metabolite norketamine. No human data are available on the relative contribution of norketamine to ketamine-induced analgesia and side effects. One approach to assess the ketamine and norketamine contributions is by measuring the ketamine effect at varying ketamine and norketamine plasma concentrations using the CYP450 inducer rifampicin. METHODS: In 12 healthy male volunteers the effect of rifampicin versus placebo pretreatment on S-ketamine-induced analgesia and cognition was quantified; the S-ketamine dosage was 20 mg/h for 2 h. The relative ketamine and norketamine contribution to effect was estimated using a linear additive population pharmacokinetic-pharmacodynamic model. RESULTS: S-ketamine produced significant analgesia, psychotropic effects (drug high), and cognitive impairment (including memory impairment and reduced psychomotor speed, reaction time, and cognitive flexibility). Modeling revealed a negative contribution of S-norketamine to S-ketamine- induced analgesia and absence of contribution to cognitive impairment. At ketamine and norketamine effect concentrations of 100 ng/ml and 50 ng/ml, respectively, the ketamine contribution to analgesia is-3.8 cm (visual analog pain score) versus a contribution of norketamine of +1.5 cm, causing an overall effect of-2.3 cm. The blood-effect site equilibration half-life ranged from 0 (cognitive flexibility) to 11.8 (pain intensity) min and was 6.1 min averaged across all endpoints. CONCLUSIONS: This first observation that norketamine produces effects in the opposite direction of ketamine requires additional proof. It can explain the observation of ketamine-related excitatory phenomena (such as hyperalgesia and allodynia) upon the termination of ketamine infusions. Copyright © 2012, the American Society of Anesthesiologists, Inc. Lippincott.


Document Type: Article
Source: Scopus

 

Kang, S.J.a , Rangaswamy, M.a , Manz, N.a , Wang, J.-C.b , Wetherill, L.c , Hinrichs, T.b , Almasy, L.d , Brooks, A.e , Chorlian, D.B.a , Dick, D.f , Hesselbrock, V.f , Kramer, J.g , Kuperman, S.g , Nurnberger, J.c , Rice, J.b , Schuckit, M.h , Tischfield, J.e , Bierut, L.J.b , Edenberg, H.J.c , Goate, A.b , Foroud, T.c , Porjesz, B.a
Family-based genome-wide association study of frontal theta oscillations identifies potassium channel gene KCNJ6
(2012) Genes, Brain and Behavior, 11 (6), pp. 712-719. 


a Henri Begleiter Neurodynamics Laboratory, Department of Psychiatry and Behavioral Sciences, SUNY Downstate Medical Center, Brooklyn, NY, United States
b Department of Psychiatry, Washington University School of Medicine, Saint Louis, MO, United States
c Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN, United States
d Department of Genetics, Texas Biomedical Research Institute, San Antonio, TX, United States
e Department of Genetics, Rutgers University, Piscataway, NJ, United States
f Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA, United States
g Department of Psychiatry, University of Iowa College of Medicine, Iowa City, IA, United States
h Department of Psychiatry, University of California-San Diego, La Jolla, CA, United States

Abstract
Event-related oscillations (EROs) represent highly heritable neuroelectric correlates of cognitive processes that manifest deficits in alcoholics and in offspring at high risk to develop alcoholism. Theta ERO to targets in the visual oddball task has been shown to be an endophenotype for alcoholism. A family-based genome-wide association study was performed for the frontal theta ERO phenotype using 634 583 autosomal single nucleotide polymorphisms (SNPs) genotyped in 1560 family members from 117 families densely affected by alcohol use disorders, recruited in the Collaborative Study on the Genetics of Alcoholism. Genome-wide significant association was found with several SNPs on chromosome 21 in KCNJ6 (a potassium inward rectifier channel; KIR3.2/GIRK2), with the most significant SNP at P = 4.7 × 10 -10). The same SNPs were also associated with EROs from central and parietal electrodes, but with less significance, suggesting that the association is frontally focused. One imputed synonymous SNP in exon four, highly correlated with our top three SNPs, was significantly associated with the frontal theta ERO phenotype. These results suggest KCNJ6 or its product GIRK2 account for some of the variations in frontal theta band oscillations. GIRK2 receptor activation contributes to slow inhibitory postsynaptic potentials that modulate neuronal excitability, and therefore influence neuronal networks. © 2012 The Authors. Genes, Brain and Behavior © 2012 Blackwell Publishing Ltd and International Behavioural and Neural Genetics Society.


Author Keywords
Alcoholism;  EEG;  GWAS;  KCNJ6;  Oscillations


Document Type: Article
Source: Scopus

 

Wang, Y.a , Szretter, K.J.a b c , Vermi, W.a d , Gilfillan, S.a , Rossini, C.d , Cella, M.a , Barrow, A.D.a e , Diamond, M.S.a b c , Colonna, M.a
IL-34 is a tissue-restricted ligand of CSF1R required for the development of Langerhans cells and microglia
(2012) Nature Immunology, 13 (8), pp. 753-760. 


a Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, United States
b Department of Medicine, Washington University School of Medicine, St. Louis, MO, United States
c Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, United States
d Department of Pathology, University of Brescia, Brescia, Italy
e Department of Pathology, University of Cambridge, Cambridge, United Kingdom

Abstract
The differentiation of bone marrow-derived progenitor cells into monocytes, tissue macrophages and some dendritic cell (DC) subtypes requires the growth factor CSF1 and its receptor, CSF1R. Langerhans cells (LCs) and microglia develop from embryonic myeloid precursor cells that populate the epidermis and central nervous system (CNS) before birth. Notably, LCs and microglia are present in CSF1-deficient mice but absent from CSF1R-deficient mice. Here we investigated whether an alternative CSF1R ligand, interleukin 34 (IL-34), is responsible for this discrepancy. Through the use of IL-34-deficient (Il34 LacZ/LacZ) reporter mice, we found that keratinocytes and neurons were the main sources of IL-34. Il34 LacZ/LacZ mice selectively lacked LCs and microglia and responded poorly to skin antigens and viral infection of the CNS. Thus, IL-34 specifically directs the differentiation of myeloid cells in the skin epidermis and CNS. © 2012 Nature America, Inc. All rights reserved.


Document Type: Article
Source: Scopus

 

Blondel, B.a b , Schwab, F.a , Ungar, B.a , Smith, J.c , Bridwell, K.d , Glassman, S.e , Shaffrey, C.c , Farcy, J.-P.f , Lafage, V.a
Impact of magnitude and percentage of global sagittal plane correction on health-related quality of life at 2-years follow-up
(2012) Neurosurgery, 71 (2), pp. 341-348. 

a Spine Division, Hospital for Joint Diseases, New York University, New York, NY 10003, United States
b Université Aix-Marseille, Marseille, France
c Department of Neurological Surgery, University of Virginia, Charlottesville, VA, United States
d Spine Department, Washington University School of Medicine, Saint Louis, MO, United States
e Spine Institute for Special Surgery, University of Louisville, Kentucky, United States
f Maimonides Medical Center, Brooklyn, NY, United States

Abstract
BACKGROUND: Sagittal plane malalignment has been established as the main radiographic driver of disability in adult spinal deformity (ASD). OBJECTIVE: To evaluate the amount of sagittal correction needed for a patient to perceive improvement (minimal clinically important difference, MCID) in health-related quality of life (HRQOL) scores. METHODS: This was a multicenter, retrospective analysis of prospectively consecutively enrolled ASD patients. Inclusion criterion was a sagittal vertical axis (SVA) >80 mm. Demographic, radiographic, and HRQOL preoperative and 2-year postsurgery data were collected. Surgical treatment was categorized based on SVA correction: <60 mm, 60 mm to 120 mm, and >120 mm. Changes in parameters were analyzed using paired t test, 1-way analysis of variance, and χ test. RESULTS: Seventy-six patients (preoperative SVA = 140 mm) were analyzed; each subgroup revealed significant HRQOL improvements following surgery. Compared with the <60 mm correction group, the likelihood of reaching MCID was significantly improved for the >120 mm group (Oswestry Disability Index) but not for the 60 mm to 120 mm group. A significantly greater likelihood of reaching MCID thresholds was observed for corrections above 66% of preoperative SVA. CONCLUSION: Best HRQOL outcomes for ASD patients with severe sagittal plane deformity were obtained with a correction >120 mm for SVA and at least 66% of correction. Although lesser amounts of SVA correction yielded clinical improvement, the rate of MCID threshold improvement was not significantly different for mild or modest corrections. These results underline the need for complete sagittal plane deformity correction if high rates of HRQOL benefit are sought for patients with marked sagittal plane deformity. Copyright © 2012 by the Congress of Neurological Surgeons.


Author Keywords
Deformity;  Health-related quality of life;  Outcomes;  Sagittal balance Sagittal vertical axis


Document Type: Article
Source: Scopus

 

Leighton, B.L., Wall, M.H., Lockhart, E.M., Phillips, L.E., Zatta, A.J.
In reply
(2012) Anesthesiology, 117 (2), pp. 423-424. 


Washington University in St. Louis, School of Medicine, St. Louis, MI, United States

Document Type: Letter
Source: Scopus

 

Breshears, J.D.a , Gaona, C.M.b , Roland, J.L.c , Sharma, M.b , Bundy, D.T.b , Shimony, J.S.d , Rashid, S.e , Eisenman, L.N.e , Hogan, R.E.e , Snyder, A.Z.d , Leuthardt, E.C.b c
Mapping sensorimotor cortex with slow cortical potential resting-state networks while awake and under anesthesia
(2012) Neurosurgery, 71 (2), pp. 305-316. 


a Washington University School of Medicine, St. Louis, MI, United States
b Department of Biomedical Engineering, Washington University, St. Louis, MI, United States
c Department of Neurosurgery, Washington University in St. Louis, School of Medicine, 660 S Euclid, St. Louis, MO 63130, United States
d Mallinckrodt Institute of Radiology, United States
e Department of Neurology, Washington University School of Medicine, St. Louis, MI, United States

Abstract
BACKGROUND: The emerging insight into resting-state cortical networks has been important in our understanding of the fundamental architecture of brain organization. These networks, which were originally identified with functional magnetic resonance imaging, are also seen in the correlation topography of the infraslow rhythms of local field potentials. Because of the fundamental nature of these networks and their independence from task-related activations, we posit that, in addition to their neuroscientific relevance, these slow cortical potential networks could play an important role in clinical brain mapping. OBJECTIVE: To assess whether these networks would be useful in identifying eloquent cortex such as sensorimotor cortex in patients both awake and under anesthesia. METHODS: This study included 9 subjects undergoing surgical treatment for intractable epilepsy. Slow cortical potentials were recorded from the cortical surface in patients while awake and under propofol anesthesia. To test brain-mapping utility, slow cortical potential networks were identified with data-driven (seed-independent) and anatomy-driven (seed-based) approaches. With electrocortical stimulation used as the gold standard for comparison, the sensitivity and specificity of these networks for identifying sensorimotor cortex were calculated. RESULTS: Networks identified with a data-driven approach in patients under anesthesia and awake were 90% and 93% sensitive and 58% and 55% specific for sensorimotor cortex, respectively. Networks identified with systematic seed selection in patients under anesthesia and awake were 78% and 83% sensitive and 67% and 60% specific, respectively. CONCLUSION: Resting-state networks may be useful for tailoring stimulation mapping and could provide a means of identifying eloquent regions in patients while under anesthesia. Copyright © 2012 by the Congress of Neurological Surgeons.


Author Keywords
Brain mapping;  Electrocorticography;  Functional networks;  Sensorimotor cortex;  Slow cortical potential


Document Type: Article
Source: Scopus

 

Nagele, P.a , Pal, S.a , Brown, F.b , Blood, J.a , Miller, J.P.c , Johnston, J.a
Postoperative QT interval prolongation in patients undergoing noncardiac surgery under general anesthesia
(2012) Anesthesiology, 117 (2), pp. 321-328. 


a Department of Anesthesiology, Washington University, School of Medicine, 660 S. Euclid Avenue, St. Louis, MI 63110, United States
b Division of Clinical and Translational Research, Department of Anesthesiology, Washington University, United States
c Division of Biostatistics, Washington University, United States

Abstract
BACKGROUND: Abnormal cardiac repolarization, indicated by a prolongation of the QT interval, increases the risk for torsades de pointes, a potentially life-threatening arrhythmia. Many perioperatively administered drugs and conditions prolong the QT interval. Despite several reports of perioperative torsades de pointes, systematic evidence regarding perioperative QT interval prolongation is limited. METHODS: Serial postoperative 12-lead electrocardiograms were obtained from 469 adult patients undergoing major noncardiac surgery under general anesthesia. Heart rate corrected QT-interval duration (Fridericia formula) was the primary outcome. All perioperatively administered drugs were recorded. Emphasis was placed on absolute QTc prolongation greater than 500 ms and relative increases of 30 and 60 ms. RESULTS: At the end of surgery, 80% of the patients (345 of 429) experienced a significant QTc interval prolongation (ΔQTc 23 ± 26 ms (mean and SD), 95% CI 20-25 ms, P less than 0.001). Approximately 51% (219 of 429) had a QTc greater than 440 ms, and 4% (16 of 429) a QTc greater than 500 ms. In 39% (166 of 429), the ΔQTc was greater than 30 ms, in 8% (34 of 429) >60 ms, and in greater than 0.5% (2 of 429) >100 ms. No changes in ΔQTc occurred at subsequent time points. One patient developed torsades de pointes with a ΔQTc: 29 ms (0.4% incidence rate). Several drugs had a large effect on ΔQTc: isoflurane, methadone, ketorolac, cefoxitin, zosyn, unasyn, epinephrine, ephedrine, and calcium. Postoperative body temperature had a weak negative correlation with ΔQTc (r =-0.15, P = 0.02); serum magnesium, potassium, and calcium concentrations were not correlated. CONCLUSION: Postoperative QT-interval prolongation is common. Several perioperatively administered drugs are associated with a substantial QT-interval prolongation. The exact cause and its clinical relevance are, however, unclear. Nevertheless, an association between postoperative QT prolongation and risk for torsades de pointes is likely. Copyright © 2012, the American Society of Anesthesiologists, Inc. Lippincott.


Document Type: Article
Source: Scopus

 

Bayly, P.V.a b , Clayton, E.H.a , Genin, G.M.a
Quantitative imaging methods for the development and validation of brain biomechanics models
(2012) Annual Review of Biomedical Engineering, 14, pp. 369-396. 

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

Abstract
Rapid deformation of brain tissue in response to head impact or acceleration can lead to numerous pathological changes, both immediate and delayed. Modeling and simulation hold promise for illuminating the mechanisms of traumatic brain injury (TBI) and for developing preventive devices and strategies. However, mathematical models have predictive value only if they satisfy two conditions. First, they must capture the biomechanics of the brain as both a material and a structure, including the mechanics of brain tissue and its interactions with the skull. Second, they must be validated by direct comparison with experimental data. Emerging imaging technologies and recent imaging studies provide important data for these purposes. This review describes these techniques and data, with an emphasis on magnetic resonance imaging approaches. In combination, these imaging tools promise to extend our understanding of brain biomechanics and improve our ability to study TBI in silico.Copyright © 2012 by Annual Reviews. All rights reserved.


Author Keywords
Brain-skull interaction;  Elastography;  Magnetic resonance imaging;  MRI;  TBI;  Traumatic brain injury


Document Type: Review
Source: Scopus

 

Greene, D.J.a b , Zaidel, E.a
Spatial orienting of attention simultaneously cued by automatic social and nonsocial cues
(2012) Experimental Brain Research, 221 (1), pp. 115-122. 


a Department of Psychology, University of California Los Angeles, 1285 Franz Hall, Los Angeles, CA 90095-1563, United States
b Washington University School of Medicine, 4525 Scott Avenue, St. Louis, MO 63110, United States

Abstract
The appearance of a stimulus in the periphery and the direction of another person's eye gaze have both been shown to automatically orient attention toward the stimulus and the gazed-at location, respectively. In the present experiment, we examined the effects of viewing both a peripheral stimulus and an eye gaze stimulus simultaneously in order to determine whether one is "more automatic" (i.e., faster, dominates) than the other and whether the two processes interact. Using a spatial cueing paradigm, we measured latency of localization of a target stimulus that was validly or invalidly cued by an uninformative (i.e., nonpredictive) peripheral cue, an uninformative eye gaze cue, or both simultaneously (double cue). We included a short and a long cue-target interval in order to investigate the early and late facilitatory and inhibitory effects of the two processes. Results demonstrated that when the double cues were consistent with each other (indicating the same target location), the effects, both early and late, were the same as when the peripheral cue was presented alone. When the double cues were inconsistent (indicating opposite target locations), the late effect was the same as the peripheral cue, but the early effect was intermediate between the two types of cues. Our results better support an interactive, rather than an additive relationship between social and nonsocial automatic orienting. The double cue conditions that showed similar effects to the peripheral cues suggest that the peripheral cue dominates. © 2012 Springer-Verlag.


Author Keywords
Exogenous orienting;  Inhibition of return;  Reflexive attention;  Social cues;  Spatial attention


Document Type: Article
Source: Scopus

 

Andriola, E.a , Donfrancesco, R.b , Zaninotto, S.c , Di Trani, M.d , Cruciani, A.C.b , Innocenzi, M.b , Marano, A.e , Pommella, L.f , Cloninger, C.R.g
The junior temperament and character inventory: Italian validation of a questionnaire for the measurement of personality from ages 6 to 16 years
(2012) Comprehensive Psychiatry, 53 (6), pp. 884-892. 


a Developmental Unit, Beck Institute, 00185 Rome, Italy
b Sandro Pertini Hospital, Asl RM B, 00158 Rome, Italy
c Villa Delle Querce Clinical Rehabilitation Institute, 00040 Nemi, Rome, Italy
d Department of Dynamic and Clinical Psychology, University Sapienza, 00185 Rome, Italy
e Department of Social and Developmental Psychology, University Sapienza, 00185 Rome, Italy
f Giugliano in Campania Primary School, 80014 Giugliano in Campania, Naples, Italy
g Department of Psychiatry, School of Medicine, Washington University in St. Louis, St. Louis, MO 63110, United States

Abstract
The Junior Temperament and Character Inventory (JTCI) has been developed for the assessment of the personality in individuals 6 to 14 years old according to the psychobiological model of Cloninger. The aim of the present study was to evaluate the psychometric properties of an Italian version of JTCI. The sample included 459 subjects ranging in age from 6 to 15.9 years. Starting from the original parent version, an Italian version of JTCI was developed and administered to parents recruited in primary schools of Lazio and Campania. Using statistically appropriate methods for the analysis of dichotomous variables (binary coded), we analyzed the factor structure, the internal consistency, and the test-retest reliability. The architecture of the JTCI was consistent with the original hypothesis of the Cloninger model. Parent reports of each of the JTCI dimensions had good internal consistency and test-retest reliability over 3 months. Regarding the analysis of risk personality traits, significant correlations were found between several JTCI factors and Strengths and Difficulties Questionnaire scales. The JTCI is useful in research and in clinical practice to evaluate the role of temperament and character dimensions in psychopathology. © 2012 Elsevier Inc.


Document Type: Article
Source: Scopus

 

Keane, B.P.a b c , Silverstein, S.M.a b , Barch, D.M.d , Carter, C.S.e , Gold, J.M.f , Kovács, I.g , MacDonald III, A.W.h , Ragland, J.D.e , Strauss, M.E.i
The spatial range of contour integration deficits in schizophrenia
(2012) Experimental Brain Research, 220 (3-4), pp. 251-259. 


a Division of Schizophrenia Research, University Behavioral HealthCare, University of Medicine and Dentistry of New Jersey, 151 Centennial Ave, Piscataway, NJ 08854, United States
b Department of Psychiatry, UMDNJ - Robert Wood Johnson Medical School, 671 Hoes Lane, Piscataway, NJ 08854, United States
c Center for Cognitive Science, Rutgers University, New Brunswick, 152 Frelinghuysen Road, Piscataway, NJ 08854, United States
d Departments of Psychology, Psychiatry, and Radiology, Washington University in St. Louis, Box 1125, One Brookings Drive, St. Louis, MO 63130, United States
e University of California, Davis, 4701 X Street, Sacramento, CA 95817, United States
f Maryland Psychiatric Research Center, University of Maryland School of Medicine, P.O. Box 21247, Baltimore, MD 21228, United States
g Department of Cognitive Science, Budapest University of Technology and Economics, 1 Egry J. u., Bldg T., Budapest 1111, Hungary
h Department of Psychology, University of Minnesota, N426 Elliott Hall, 75 E. River Rd., Minneapolis, MN 55455, United States
i Department of Psychological Sciences, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106-7123, United States

Abstract
Contour integration (CI) refers to the process that represents spatially separated elements as a unified edge or closed shape. Schizophrenia is a psychiatric disorder characterized by symptoms such as hallucinations, delusions, disorganized thinking, inappropriate affect, and social withdrawal. Persons with schizophrenia are impaired at CI, but the specific mechanisms underlying the deficit are still not clear. Here, we explored the hypothesis that poor patient performance owes to reduced feedback or impaired longer-range lateral connectivity within early visual cortex - functionally similar to that found in 5- to 6-year old children. This hypothesis predicts that as target element spacing increases from .7 to 1.4° of visual angle, patient impairments will become more pronounced. As a test of the prediction, 25 healthy controls and 36 clinically stable, asymptomatic persons with schizophrenia completed a CI task that involved determining whether a subset of Gabor elements formed a leftward or rightward pointing shape. Adjacent shape elements were spaced at either .7 or 1.4° of visual angle. Difficulty in each spacing condition depended on the number of noise elements present. Patients performed worse than controls overall, both groups performed worse with the larger spacing, and the magnitude of the between-group difference was not amplified at the larger spacing. These results show that CI deficits in schizophrenia cannot be explained in terms of a reduced spatial range of integration, at least not when the shape elements are spaced within 1.5°. Later-developing, low-level integrative mechanisms of lateral connectivity and feedback appear not to be differentially impaired in the illness. © Springer-Verlag 2012.


Author Keywords
Contour integration;  Grouping;  Perceptual organization;  Schizophrenia;  Spatial range;  Visual integration


Document Type: Article
Source: Scopus

 

Park, D.a , Hou, X.b , Sweedler, J.V.b , Taghert, P.H.a
Therapeutic peptide production in Drosophila
(2012) Peptides, 36 (2), pp. 251-256. 


a Department of Anatomy and Neurobiology, Washington University, School of Medicine, 660 S. Euclid Ave., St. Louis, MO 63110, United States
b Department of Chemistry, Beckman Institute, University of Illinois, 600 S. Mathews Ave., 63-5, Urbana, IL 61801, United States

Abstract
Bioactive peptides are important therapeutic drugs, yet conventional methods of peptide synthesis are challenged to meet increasing demand. We developed a novel and efficient means of metabolic engineering: therapeutic peptide production in Drosophila and as a proof of concept, we demonstrate production of fully matured human insulin. This in vivo system offers an innovative means to produce valuable bioactive peptides for therapies, its inherent flexibility facilitates drug development, and its ease of producing fully processed peptides simplifies metabolic engineering of new peptide products. © 2012 Elsevier Inc. All rights reserved.


Author Keywords
DIMM;  Drosophila;  Insulin;  Theraputic peptides


Document Type: Article
Source: Scopus

 

Fleisher, L.A.a , Evers, A.S.b , Wiener-Kronish, J.c , Ulatowski, J.A.d
What are we looking for?: The question of resident selection
(2012) Anesthesiology, 117 (2), pp. 230-231. 

a Departments of Anesthesiology and Critical Care, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States
b Department of Anesthesiology, Washington University School of Medicine, St. Louis, MI, United States
c Anaesthetics and Anesthesia Departments, Harvard Medical School, Massachusetts General Hospital, Boston, MA, United States
d Departments of Anesthesiology and Critical Care, Johns Hopkins University, Baltimore, MD, United States

Document Type: Editorial
Source: Scopus

 

Belden, A.C., Gaffrey, M.S., Luby, J.L.
Relational Aggression in Children with Preschool-Onset Psychiatric Disorders
(2012) Journal of the American Academy of Child and Adolescent Psychiatry, . Article in Press. 


Early Emotional Development Program (EEDP) at the Washington University School of Medicine in St. Louis

Abstract
Objective: The role of preschool-onset (PO) psychiatric disorders as correlates and/or risk factors for relational aggression during kindergarten or first grade was tested in a sample of 146 preschool-age children (age 3 to 5.11 years). Method: Axis-I diagnoses and symptom scores were derived using the Preschool Age Psychiatric Assessment. Children's roles in relational aggression as aggressor, victim, aggressive-victim, or nonaggressor/nonvictim were determined at preschool and again 24 months later at elementary school entry. Results: Preschoolers diagnosed with PO psychiatric disorders were three times as likely as the healthy preschoolers to be classified aggressors, victims, or aggressive-victims. Children diagnosed with PO disruptive, depressive, and/or anxiety disorders were at least six times as likely as children without PO psychiatric disorders to become aggressive-victims during elementary school after covarying for other key risk factors. Conclusions: Findings suggested that PO psychiatric disorders differentiated preschool and school-age children's roles in relational aggression based on teacher report. Recommendations for future research and preventative intervention aimed at minimizing the development of relational aggression in early childhood by identifying and targeting PO psychiatric disorders are made. © 2012 American Academy of Child and Adolescent Psychiatry.


Author Keywords
aggressive-victim;  bullying;  preschool psychiatric disorders;  relational aggression


Document Type: Article in Press
Source: Scopus

 

Wright, P.W.a b , Heaps, J.M.c , Shimony, J.S.d , Thomas, J.B.b , Ances, B.M.a b
The effects of HIV and combination antiretroviral therapy on white matter integrity
(2012) AIDS, 26 (12), pp. 1501-1508. 


a Department of Biomedical Engineering, Washington University, Saint Louis, United States
b Department of Neurology, Washington University, Saint Louis, United States
c Department of Psychology, University of Missouri Saint Louis, United States
d Department of Radiology, Washington University in Saint Louis, Saint Louis, MO, United States

Abstract
Objective: HIV preferentially affects white matter in the brain. Although combination antiretroviral therapy (cART) reduces HIV viral load within the brain, continued inflammation can persist. We investigated the effect of HIV and cART on white matter integrity. Design: We used diffusion tensor imaging (DTI) to examine the effects of HIV and cART on white matter integrity within the corpus callosum and centrum semiovale (CSO). Methods: Neuropsychological testing and DTI measures (fractional anisotropy, mean diffusivity, axial diffusivity, radial diffusivity) were obtained from 21 HIV-uninfected controls, 21 HIV-infected patients naive to cART (HIV +cART-), and 21 HIV+ patients receiving stable cART (HIV +cART+). A subset of the HIV +cART-individuals (n=10) was assessed before and 6 months after receiving medications. Differences among the cross-sectional groups were assessed using an analysis of variance, whereas paired t-tests evaluated longitudinal changes. Results: HIV +cART-participants had significantly lower mean diffusivity, axial diffusivity, and radial diffusivity for the corpus callosum and CSO compared to HIV-controls and HIV +cART+ individuals. No significant difference existed between HIV-controls and HIV +cART+ patients. cART initiation significantly improved mean diffusivity, radial diffusivity, and axial diffusivity, but not fractional anisotropy, in the corpus callosum and CSO in some HIV-infected patients. Conclusion: Observed decreases in DTI parameters between HIV +cART+ and HIV +cART-individuals could reflect the presence of inflammatory cells or cytotoxic edema in HIV +cART-patients. Initiating cART could lead to a reduction in neuro-inflammation and improvement in DTI measures. Future DTI studies may be useful for evaluating the efficacy higher brain penetrating cART regimens. © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins.


Author Keywords
centrum semiovale;  combination antiretroviral therapy;  corpus callosum;  diffusion tensor imaging;  HIV


Document Type: Article
Source: Scopus

 

Vitiello, B.a , Riddle, M.A.b , Yenokyan, G.b , Axelson, D.A.c , Wagner, K.D.d , Joshi, P.e , Walkup, J.T.f , Luby, J.g , Birmaher, B.c , Ryan, N.D.c , Emslie, G.h , Robb, A.e , Tillman, R.g
Treatment Moderators and Predictors of Outcome in the Treatment of Early Age Mania (TEAM) Study
(2012) Journal of the American Academy of Child and Adolescent Psychiatry, . Article in Press. 


a National Institute of Mental Health (NIMH)
b Johns Hopkins University
c University of Pittsburgh
d University of Texas at Galveston
e Children National Medical Center-George Washington University
f Cornell University
g Washington University in St. Louis
h University of Texas-Southwestern Medical Center

Abstract
Objective: Both the diagnosis and treatment of bipolar disorder in youth remain the subject of debate. In the Treatment of Early Age Mania (TEAM) study, risperidone was more effective than lithium or divalproex in children diagnosed with bipolar mania and highly comorbid with attention-deficit/hyperactivity disorder (ADHD). We searched for treatment moderators and predictors of outcome. Method: TEAM was a multi-site, 8-week, randomized clinical trial of risperidone, lithium, or divalproex in 279 medication-naïve patients, aged 6 through 15 years, with a DSM-IV diagnosis of bipolar disorder currently in manic or mixed phase. Outcome measures included binary end-of-treatment responder status and change in the Kiddie Schedule for Affective Disorders and Schizophrenia (K-SADS) Mania Rating Scale (KMRS). Baseline demographics and clinical characteristics were tested as modifiers of treatment effect and as overall predictors of outcome. Results: Moderator effects were detected for site, ADHD, and obesity. Across sites, the response ratio (RR) for risperidone versus lithium ranged from 1.2 (95% confidence interval [CI] = 0.8-1.7) to 8.3 (95% CI = 1.1-60.8), and for risperidone versus divalproex from 1.3 (95% CI = 0.8-2.2) to 10.5 (95% CI = 1.4-77.7). The RR for risperidone versus lithium was 2.1 for patients with ADHD, but 1.0 for those without ADHD, and 2.3 (95% CI = 1.6-3.3) for nonobese patients, but 1.1 (95% CI = 0.6-2.0) for obese ones. Older age and less severe ADHD symptoms were associated with greater improvement on the KMRS. Conclusions: Risperidone was more effective than lithium or divalproex across the demographics and clinical characteristics of the sample, but the magnitude of its effect was influenced by site-related characteristics and presence of ADHD. Clinical trial registration information-Treatment of Early Age Mania; http://clinicaltrials.gov/; NCT00057681. © 2012 American Academy of Child and Adolescent Psychiatry.


Author Keywords
bipolar;  moderators;  predictors;  treatment


Document Type: Article in Press
Source: Scopus

 

Lee, A.G.a b , Oetting, T.A.b , Blomquist, P.H.c , Bradford, G.d , Culican, S.M.e , Kloek, C.f , Krishnan, C.g , Lauer, A.K.h , Levi, L.i , Naseri, A.j , Rubin, S.E.k , Scott, I.U.l , Tao, J.m , Tuli, S.n , Wright, M.M.o , WuDunn, D.p , Zimmerman, M.B.b
A Multicenter Analysis of the Ophthalmic Knowledge Assessment Program and American Board of Ophthalmology Written Qualifying Examination Performance
(2012) Ophthalmology, . Article in Press. 


a The Methodist Hospital, Houston, Texas.; the Department of Neurology and Neurosurgery, Weill Cornell Medical College, New York, New York; The University of Texas Medical Branch, Galveston, Texas; and Baylor College of Medicine, Houston, Texas
b Department of Ophthalmology, The University of Iowa Hospitals and Clinics, Iowa City, Iowa
c University of Texas Southwestern Medical Center, Dallas, Texas
d West Virginia University, Morgantown, West Virginia
e Washington University School of Medicine, St. Louis, Missouri
f Massachusetts Eye and Ear Infirmary, Boston, Massachusetts
g Tufts University, Boston, Massachusetts
h Casey Eye Institute, Oregon Health and Science University, Portland, Oregon
i University of California, San Diego, San Diego, California
j University of California, San Francisco, San Francisco, California
k North Shore-Long Island Jewish Health System, Great Neck, New York
l Penn State College of Medicine, Hershey, Pennsylvania
m University of California, Irvine, Irvine, California
n University of Florida, Gainesville, Florida
o University of Minnesota, Minneapolis, Minnesota
p Indiana University, Indianapolis, Indiana

Abstract
Objective: To compare the performance on the American Board of Ophthalmology Written Qualifying Examination (WQE) with the performance on step 1 of the United States Medical Licensing Examination (USMLE) and the Ophthalmic Knowledge Assessment Program (OKAP) examination for residents in multiple residency programs. Design: Comparative case series. Participants: Fifteen residency programs with 339 total residents participated in this study. The data were extracted from the 5-year American Board of Ophthalmology report to each participating program in 2009 and included residency graduating classes from 2003 through 2007. Residents were included if data were available for the USMLE, OKAP examination in ophthalmology years 1 through 3, and the WQE score. Residents were excluded if one or more of the test scores were not available. Methods: Two-sample t tests, logistic regression analysis, and receiver operating characteristic (ROC) curves were used to examine the association of the various tests (USMLE, OKAP examination year 1, OKAP examination year 2, OKAP examination year 3, and maximum OKAP examination score) as a predictor for a passing or failing grade on the WQE. Main Outcome Measures: The primary outcome measure of this study was first time pass rate for the WQE. Results: Using ROC analysis, the OKAP examination taken at the third year of ophthalmology residency best predicted performance on the WQE. For the OKAP examination taken during the third year of residency, the probability of passing the WQE was at least 80% for a score of 35 or higher and at least 95% for a score of 72 or higher. Conclusions: The OKAP examination, especially in the third year of residency, can be useful to residents to predict the likelihood of success on the high-stakes WQE examination. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article. © 2012 American Academy of Ophthalmology.


Document Type: Article in Press
Source: Scopus

 

Agrawal, A.a , Verweij, K.J.H.b c , Gillespie, N.A.d , Heath, A.C.a , Lessov-Schlaggar, C.N.a , Martin, N.G.b , Nelson, E.C.a , Slutske, W.S.e , Whitfield, J.B.b , Lynskey, M.T.a
The genetics of addictiona translational perspective
(2012) Translational Psychiatry, 2, art. no. e140, . 


a Department of Psychiatry, Washington University School of Medicine, 660 S. Euclid, CB 8234, Saint Louis, MO 63110, United States
b Genetic Epidemiology, Queensland Institute of Medical Research, Brisbane, QLD, Australia
c School of Psychology, University of Queensland, Brisbane, QLD, Australia
d Virginia Institute of Psychiatric and Behavioral Genetics, VCU, Richmond, VA, United States
e Department of Psychological Sciences, University of Missouri, Columbia, MO, United States

Abstract
Addictions are serious and common psychiatric disorders, and are among the leading contributors to preventable death. This selective review outlines and highlights the need for a multi-method translational approach to genetic studies of these important conditions, including both licit (alcohol, nicotine) and illicit (cannabis, cocaine, opiates) drug addictions and the behavioral addiction of disordered gambling. First, we review existing knowledge from twin studies that indicates both the substantial heritability of substance-specific addictions and the genetic overlap across addiction to different substances. Next, we discuss the limited number of candidate genes which have shown consistent replication, and the implications of emerging genomewide association findings for the genetic architecture of addictions. Finally, we review the utility of extensions to existing methods such as novel phenotyping, including the use of endophenotypes, biomarkers and neuroimaging outcomes; emerging methods for identifying alternative sources of genetic variation and accompanying statistical methodologies to interpret them; the role of gene-environment interplay; and importantly, the potential role of genetic variation in suggesting new alternatives for treatment of addictions. © 2012 Macmillan Publishers Limited All rights reserved.


Author Keywords
Addiction;  drug;  genetics;  substance


Document Type: Review
Source: Scopus

 

Avery, R.A.a , Ferner, R.E.b , Listernick, R.c , Fisher, M.J.d , Gutmann, D.H.e , Liu, G.T.f
Visual acuity in children with low grade gliomas of the visual pathway: implications for patient care and clinical research
(2012) Journal of Neuro-Oncology, pp. 1-7. Article in Press. 


a Department of Neurology, Department of Pediatrics and Gilbert Neurofibromatosis Center, Children's National Medical Center, 111 Michigan Avenue, NW, Washington, 20010, United States
b Neurofibromatosis Centre, Department of Neurology, Guy's and St. Thomas' NHS Foundation Trust and In, King's College, London, United Kingdom
c Department of Pediatrics, Ann and Robert H. Lurie Children's Hospital of Chicago, Feinberg School of Medicine, Northwestern Un, Chicago, United States
d Division of Oncology, Children's Hospital of Philadelphia, and Department of Pediatrics, The Perelman School of Medicine at The University of Pennsylvania, Philadelphia, United States
e Neurofibromatosis Center, and Department of Neurology, Washington University, School of Medicine, St. Louis, United States
f Neuro-Ophthalmology Service, Children's Hospital of Philadelphia, and Departments of Neurology and O, The Perelman School of Medicine at The University of Pennsylvania, Philadelphia, United States

Abstract
Low grade gliomas affecting the visual pathway, commonly referred to as optic pathway gliomas (OPGs), have a relatively high survival rate but can cause significant vision loss. While previous treatment outcomes for tumors of the central nervous system have focused primarily on changes in tumor size or patient survival, more recently preservation of vision has also become a primary objective when treating these tumors. Visual acuity (VA) is the most testable and reliable visual parameter in young children with OPGs. Unfortunately, standardized VA assessments have neither been employed to make treatment decisions nor used as primary outcomes in clinical trials. The lack of a standardized VA assessment has also hindered the ability to interpret and compare results between studies. It is essential that all members of the multidisciplinary care team (i.e., pediatric neuro-oncologist, neurologist, neurosurgeon, and ophthalmologist) can accurately interpret VA results and properly use them to guide management decisions. Specifically, determining what constitutes a significant change in VA and the factors that may influence these results should be incorporated into collective team recommendations. This review describes the VA assessment in children with OPGs and proposes a standardized VA testing protocol for future pediatric OPG clinical treatment trials. © 2012 Springer Science+Business Media, LLC.


Author Keywords
Juvenile pilocytic astrocytoma;  Optic nerve glioma;  Visual acuity;  Visual pathways


Document Type: Article in Press
Source: Scopus

 

Lo, W.-L., Donermeyer, D.L., Allen, P.M.
A voltage-gated sodium channel is essential for the positive selection of CD4 + T cells
(2012) Nature Immunology, . Article in Press. 

Department of Immunology and Pathology, Washington University School of Medicine, St. Louis, Missouri, USA

Abstract
The sustained entry of Ca 2+ into CD4 +CD8 + double-positive thymocytes is required for positive selection. Here we identified a voltage-gated Na + channel (VGSC) that was essential for positive selection of CD4 + T cells. Pharmacological inhibition of VGSC activity inhibited the sustained Ca 2+ influx induced by positively selecting ligands and the in vitro positive selection of CD4 + but not CD8 + T cells. In vivo short hairpin RNA (shRNA)-mediated knockdown of the gene encoding a regulatory β-subunit of a VGSC specifically inhibited the positive selection of CD4 + T cells. Ectopic expression of VGSC in peripheral AND CD4 + T cells bestowed the ability to respond to a positively selecting ligand, which directly demonstrated that VGSC expression was responsible for the enhanced sensitivity. Thus, active VGSCs in thymocytes provide a mechanism by which a weak positive selection signal can induce the sustained Ca 2+ signals required for CD4 + T cell development.


Document Type: Article in Press
Source: Scopus

 

Northcott, P.A.a b , Shih, D.J.H.a c , Peacock, J.a c , Garzia, L.d , Sorana Morrissy, A.d , Zichner, T.e , Stütz, A.M.e , Korshunov, A.f , Reimand, J.g , Schumacher, S.E.h , Beroukhim, R.i j k l m n , Ellison, D.W.o , Marshall, C.R.p , Lionel, A.C.q , Mack, S.a c , Dubuc, A.a c , Yao, Y.a c , Ramaswamy, V.a c , Luu, B.d , Rolider, A.d , Cavalli, F.M.G.d , Wang, X.a c , Remke, M.d , Wu, X.d , Chiu, R.Y.B.r , Chu, A.r , Chuah, E.r , Corbett, R.D.r , Hoad, G.R.r , Jackman, S.D.r , Li, Y.r , Lo, A.r , Mungall, K.L.r , Ming Nip, K.r , Qian, J.Q.r , Raymond, A.G.J.r , Thiessen, N.r , Varhol, R.J.r , Birol, I.r , Moore, R.A.r , Mungall, A.J.r , Holt, R.s , Kawauchi, D.t , Roussel, M.F.t , Kool, M.b , Jones, D.T.W.b , Witt, H.u v , Fernandez-L, A.w , Kenney, A.M.x y , Wechsler-Reya, R.J.z , Dirks, P.aa , Aviv, T.ab , Grajkowska, W.A.ac , Perek-Polnik, M.ad , Haberler, C.C.ae , Delattre, O.af , Reynaud, S.S.ag , Doz, F.F.ah , Pernet-Fattet, S.S.ai , Cho, B.-K.aj , Kim, S.-K.aj , Wang, K.-C.aj , Scheurlen, W.ak , Eberhart, C.G.al , Fèvre-Montange, M.am , Jouvet, A.an , Pollack, I.F.ao , Fan, X.ap , Muraszko, K.M.aq , Yancey Gillespie, G.ar , Di Rocco, C.as , Massimi, L.as , Michiels, E.M.C.at , Kloosterhof, N.K.au av , French, P.J.av , Kros, J.M.aw , Olson, J.M.ax ay , Ellenbogen, R.G.az , Zitterbart, K.ba bb , Kren, L.bc , Thompson, R.C.bd , Cooper, M.K.be , Lach, B.bf bg , McLendon, R.E.bh , Bigner, D.D.bh , Fontebasso, A.bi , Albrecht, S.bj bk , Jabado, N.bl bm , Lindsey, J.C.bn , Bailey, S.bn , Gupta, N.bo , Weiss, W.A.bp , Bognár, L.bq , Klekner, A.bq , Van Meter, T.E.br , Kumabe, T.bs , Tominaga, T.bs , Elbabaa, S.K.bt , Leonard, J.R.bu , Rubin, J.B.bv , Liau, L.M.bw , Van Meir, E.G.bx , Fouladi, M.by , Nakamura, H.bz , Cinalli, G.ca , Garami, M.cb , Hauser, P.cb , Saad, A.G.cc , Iolascon, A.cd ce , Jung, S.cf , Carlotti, C.G.cg , Vibhakar, R.ch , Shin Ra, Y.ci , Robinson, S.cj ck , Zollo, M.cd ce , Faria, C.C.cl cm , Chan, J.A.cn , Levy, M.L.co , Sorensen, P.H.B.cp , Meyerson, M.j , Pomeroy, S.L.cq , Cho, Y.-J.cr , Bader, G.D.p cs ct cu , Tabori, U.cv , Hawkins, C.E.cw , Bouffet, E.cv , Scherer, S.W.q cx , Rutka, J.T.aa , Malkin, D.cy cz , Clifford, S.C.bn , Jones, S.J.M.r , Korbel, J.O.e , Pfister, S.M.da db , Marra, M.A.dc dd , Taylor, M.D.a c aa
Subgroup-specific structural variation across 1,000 medulloblastoma genomes
(2012) Nature, . Article in Press. 


a 1] Developmental and Stem Cell Biology Program, The Hospital for Sick Children, 101 College Street, TMDT-11-401M, Toronto, Ontario M5G 1L7, Canada
b Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany
c Department of Laboratory Medicine and Pathobiology, University of Toronto, Medical Sciences Buildings, 1 King's College Circle, 6th Floor, Toronto, Ontario M5S 1A8, Canada
d Developmental and Stem Cell Biology Program, The Hospital for Sick Children, 101 College Street, TMDT-11-401M, Toronto, Ontario M5G 1L7, Canada
e Genome Biology, European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany
f CCU Neuropathology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 220-221, Department of Neuropathology, University of Heidelberg, Im Neuenheimer Feld 224, 69120 Heidelberg, Germany
g The Donnelly Centre, University of Toronto, 160 College Street, Room 602, Toronto, Ontario M5S 3E1, Canada
h Department of Cancer Biology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, Massachusetts 02215, USA
i 1] Department of Cancer Biology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, Massachusetts 02215, USA
j Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, Massachusetts 02215, USA
k Department of Medicine, Harvard Medical School, 25 Shattuck Street, Boston, Massachusetts 02115, USA
l Department of Medicine, Brigham and Women's Hospital, 75 Francis Street, Boston, Massachusetts 02115, USA
m Cancer Program, Broad Institute, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA
n Center for Cancer Genome Discovery, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, Massachusetts 02215, USA
o Pathology, St Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, Tennessee 38105, USA
p McLaughlin Centre and Department of Molecular Genetics, University of Toronto, 101 College Street, Toronto, Ontario M5G 1L7, Canada
q The Centre for Applied Genomics and Program in Genetics and Genome Biology, The Hospital for Sick Children, 101 College Street, TMDT-14-701, Toronto, Ontario M5G 1L7, Canada
r Michael Smith Genome Sciences Centre, BC Cancer Agency, 100-570 West 7th Avenue, Vancouver, British Columbia V5Z 4S6, Canada
s Michael Smith Genome Sciences Centre, BC Cancer Agency, 675 West 10th Avenue, Vancouver, British Columbia V5Z 1L3, Canada
t Tumour Cell Biology, St Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, Tennessee 38105, USA
u 1] Department of Pediatric Oncology, University Hospital Heidelberg, Im Neuenheimer Feld 430, 69120 Heidelberg, Germany
v Departments of Hematology and Immunology, University Hospital Heidelberg, Im Neuenheimer Feld 430, 69120 Heidelberg, Germany
w Pediatric Clinical Trials Office, Memorial Sloan-Kettering Cancer Center, 405 Lexington Avenue, New York, New York 10174, USA
x 1] Neurological Surgery, Vanderbilt Medical Center, T-4224 MCN, Nashville, Tennessee 37232-2380, USA
y Cancer Biology, Vanderbilt Medical Center, 465 21st Avenue South, MRB III 6160, Nashville, Tennessee 37232-8550, USA
z Sanford-Burnham Medical Research Institute, La Jolla, California 92037, USA
aa Department of Surgery, Division of Neurosurgery and Labatt Brain Tumour Research Centre, The Hospital for Sick Children, 555 University Avenue, Hill 1503, Toronto, Ontario M5G 1X8, Canada
ab Developmental and Stem Cell Biology Program, The Hospital for Sick Children, 101 College Street, TMDT-13-601, Toronto, Ontario M5G 1L7, Canada
ac Department of Pathology, The Children's Memorial Health Institute, Aleja Dzieci Polskich 20, 04-730 Warsaw, Poland
ad Department of Oncology, The Children's Memorial Health Institute, Aleja Dzieci Polskich 20, 04-730 Warsaw, Poland
ae Institute of Neurology, Medical University of Vienna, AKH 4J, Waehringer Gürtel 18-20, A-1097 Vienna, Austria
af INSERM U 830, Institut Curie, 26 rue d'Ulm, 75238 Paris Cedex 5, France
ag Unit of Somatic Genetics, Institut Curie, 26 rue d'Ulm, 75238 Paris Cedex 5, France
ah Department of Pediatric Oncology, Institut Curie, 26 rue d'Ulm, 75248 Paris Cedex 5, France
ai Pediatric Hematology and Oncology, CHUV University Hospital, 1011 Lausanne, Switzerland
aj Department of Neurosurgery, Division of Pediatric Neurosurgery, Seoul National University Children's Hospital, 101 Daehak-Ro Jongno-Gu, Seoul 110-744, South Korea
ak Head of Pediatrics, Cnopfsche Kinderklinik, Theodor-Kutzer-Ufer 1-3, 90419 Nuremberg, Germany
al Departments of Pathology, Ophthalmology and Oncology, John Hopkins University School of Medicine, 720 Rutland Avenue, Ross Building 558, Baltimore, Maryland 21205, USA
am INSERM U1028, CNRS UMR5292, Centre de Recherche en Neurosciences, Université de Lyon, 69336 Lyon, France
an Centre de Pathologie EST, Groupement Hospitalier EST, Université de Lyon, 69500 Bron, France
ao Department of Neurological Surgery, University of Pittsburgh School of Medicine, 4401 Penn Avenue, Pittsburgh, Pennsylvania 15224, USA
ap Departments of Neurosurgery and Cell and Developmental Biology, University of Michigan Medical School, 109 Zina Pitcher Place, 5018 BSRB, Ann Arbor, Michigan 48109, USA
aq Department of Neurosurgery, University of Michigan Medical School, 1500 E. Medical Center Drive, Taubman Center, Room 3552, Ann Arbor, Michigan 48109, USA
ar Department of Surgery, Division of Neurosurgery, University of Alabama at Birmingham, 1900 University Boulevard, THT 1052, Birmingham, Alabama 35294-0006, USA
as Pediatric Neurosurgery, Catholic University Medical School, 00186 Rome, Italy
at Department of Pediatric Oncology and Hematology, Erasmus Medical Center, Dr. Molewaterplein 50, 3000 Rotterdam, The Netherlands
au 1] Department of Pediatric Oncology and Hematology, Erasmus Medical Center, Dr. Molewaterplein 50, 3000 Rotterdam, The Netherlands
av Department of Neurology, Erasmus Medical Center, Dr. Molewaterplein 50, PO Box 2040, 3000 CA Rotterdam, The Netherlands
aw Department of Pathology, Erasmus Medical Center, Dr. Molewaterplein 50, 3015 GE Rotterdam, The Netherlands
ax 1] Clinical Research Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, D4-100, Seattle, Washington 98109, USA
ay Seattle Children's Hospital, Seattle, Washington 98104, USA
az Neurological Surgery, University of Washington School of Medicine, Harborview Medical Center, 325 Ninth Avenue, Seattle, Washington 98104, USA
ba 1] Department of Pediatric Oncology, School of Medicine, Masaryk University, Cernopolni 9, 613 00 Brno, Czech Republic
bb Department of Pediatric Oncology, University Hospital Brno, 625 00 Brno, Czech Republic
bc Department of Pathology, University Hospital Brno, Jihlavska 20, 625 00 Brno, Czech Republic
bd Neurological Surgery, Vanderbilt Medical Center, T-4224 MCN, Nashville, Tennessee 37232-2380, USA
be Department of Neurology, Vanderbilt Medical Center, 465 21st Avenue South, MRB III 6160, Nashville, Tennessee 37232-8550, USA
bf 1] Department of Pathology and Molecular Medicine, Division of Anatomical Pathology, McMaster University, Hamilton, Ontario L8S 4L8, Canada
bg Department of Pathology and Laboratory Medicine, Hamilton General Hospital, 237 Barton Street East, Hamilton, Ontario L8L 2X2, Canada
bh Department of Pathology, Duke University, DUMC 3712, Durham, North Carolina 27710, USA
bi Division of Experimental Medicine, McGill University, 4060 Ste Catherine West, Montreal, Quebec H3Z 2Z3, Canada
bj 1] Department of Pathology, McGill University, Montreal, Quebec H3A 2B4, Canada
bk Department of Pathology, Montreal Children's Hospital, 2300 Tupper, Montreal, Quebec H3H 1P3, Canada
bl 1] Division of Experimental Medicine, McGill University, 4060 Ste Catherine West, Montreal, Quebec H3Z 2Z3, Canada
bm Department of Pediatrics, Division of Hemato-Oncology, McGill University, Montreal, Quebec H3H 1P3, Canada
bn Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne NE1 4LP, United Kingdom
bo Departments of Neurological Surgery and Pediatrics, University of California San Francisco, 505 Parnassus Avenue, Room M779, San Francisco, California 94143-0112, USA
bp Departments of Neurology, Pediatrics, and Neurosurgery, University of California San Francisco, The Helen Diller Family Cancer Research Building 1450 3rd Street, Room HD-220, MC 0520, San Francisco, California 94158, USA
bq Department of Neurosurgery, University of Debrecen, Medical and Health Science Centre, Móricz Zs. Krt. 22., 4032 Debrecen, Hungary
br Pediatrics, Virginia Commonwealthy University, School of Medicine, Box 980646, Pediatric Hematology-Oncology, 1101 East Marshall Street, Richmond, Virginia 23298-0646, USA
bs Department of Neurosurgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan
bt Department of Neurosurgery, Division of Pediatric Neurosurgery, St Louis University School of Medicine, 1465 South Grand Boulevard, Suite 3707, St Louis, Missouri 63104, USA
bu Department of Neurosurgery, Division of Pediatric Neurosurgery, Washington University School of Medicine and St Louis Children's Hospital, Campus Box 8057, 660 South Euclid Avenue, St Louis, Missouri 63110, USA
bv Departments of Pediatrics, Anatomy and Neurobiology, Washington University School of Medicine and St Louis Children's Hospital, Campus Box 8208, 660 South Euclid Avenue, St Louis, Missouri 63110, USA
bw Department of Neurosurgery, David Geffen School of Medicine at UCLA, 10833 Le Conte Avenue, Campus 690118, Los Angeles, California 90095, USA
bx Laboratory of Molecular Neuro-Oncology, Departments of Neurosurgery and Hematology and Medical Oncology, School of Medicine and Winship Cancer Institute, Emory University, 1365C Clifton Road NE, Atlanta, Georgia 30322, USA
by Division of Oncology, University of Cincinnati, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA
bz Department of Neurosurgery, Kumamoto University Graduate School of Medical Science, 1-1-1, Honjo, Kumamoto 860-8556, Japan
ca Paediatric Neurosurgery, Ospedale Santobono-Pausilipon, 80145 Naples, Italy
cb 2nd Department of Pediatrics, Semmelweis University, 1085 Budapest, Hungary
cc Pathology, University of Arkansas for Medical Sciences, 1 Children's Way, lot 820, Little Rock, Arkansas 72202, USA
cd 1] Dipartimento di Biochimica e Biotecnologie Mediche, University of Naples, Via Pansini 5, 80145 Naples, Italy
ce CEINGE Biotecnologie Avanzate, Via Gaetano Salvatore 486, 80145 Naples, Italy
cf Department of Neurosurgery, Chonnam National University Research Institute of Medical Sciences, Chonnam National University Hwasun Hospital and Medical School, 322 Seoyang-ro, Hwasun-eup, Hwasun-gun, Chonnam 519-763, South Korea
cg Department of Surgery and Anatomy, Faculty of Medicine of Ribeirão Preto, Universidade de São Paulo, Brazil, Avenida Bandeirantes, 3900, Monte Alegre, 14049-900, Rebeirao Preto, São Paulo, Brazil
ch Pediatrics, University of Colorado Denver, 12800 19th Avenue, Aurora, Colorado 80045, USA
ci Department of Neurosurgery, University of Ulsan, Asan Medical Center, Seoul, 138-736, South Korea
cj 1] Division of Pediatric Neurosurgery, Case Western Reserve, Cleveland, Ohio 44106, USA
ck Rainbow Babies and Children's, Cleveland, Ohio 44106, USA
cl 1] Division of Neurosurgery, Hospital de Santa Maria, Centro Hospitalar Lisboa Norte EPE, 1169-050, Lisbon, Portugal
cm Cell Biology Program, The Hospital for Sick Children, 101 College Street, TMDT-401-J, Toronto, Ontario M5G 1L7, Canada
cn Department of Pathology and Laboratory Medicine, University of Calgary, 3330 Hospital Drive NW, HRIC 2A25A, Calgary, Alberta T2N 4N1, Canada
co UCSD Division of Neurosurgery, Rady Children's Hospital San Diego, 8010 Frost Street, Suite 502, San Diego, California 92123, USA
cp Department of Molecular Oncology, British Columbia Cancer Research Centre, 675 West 10th Avenue, Vancouver, British Columbia V5Z 1L3, Canada
cq Department of Neurology, Harvard Medical School, Children's Hospital Boston, Fegan 11, 300 Longwood Avenue, Boston, Massachusetts 02115, USA
cr Department of Neurology and Neurological Sciences, Stanford University School of Medicine, 1201 Welch Road, MSLS Building, Rm P213, Stanford, California 94305, USA
cs 1] The Donnelly Centre, University of Toronto, 160 College Street, Room 602, Toronto, Ontario M5S 3E1, Canada
ct Banting and Best Department of Medical Research, University of Toronto, Toronto, Ontario M5G 1L6, Canada
cu Samuel Lunenfeld Research Institute at Mount Sinai Hospital, University of Toronto, Toronto M5G 1X5, Ontario, Canada
cv Department of Haematology and Oncology, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario M5G 1X8, Canada
cw Department of Pathology, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario M5G 1X8, Canada
cx 1] McLaughlin Centre and Department of Molecular Genetics, University of Toronto, 101 College Street, Toronto, Ontario M5G 1L7, Canada
cy 1] Department of Haematology and Oncology, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario M5G 1X8, Canada
cz Department of Pediatrics, University of Toronto, Toronto, Ontario M5G 1X8, Canada
da 1] Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany
db Department of Pediatric Oncology, University Hospital Heidelberg, Im Neuenheimer Feld 430, 69120 Heidelberg, Germany
dc 1] Michael Smith Genome Sciences Centre, BC Cancer Agency, 675 West 10th Avenue, Vancouver, British Columbia V5Z 1L3, Canada
dd Department of Medical Genetics, University of British Columbia, 675 West 10th Avenue, Vancouver, British Columbia V5Z 1L3, Canada

Abstract
Medulloblastoma, the most common malignant paediatric brain tumour, is currently treated with nonspecific cytotoxic therapies including surgery, whole-brain radiation, and aggressive chemotherapy. As medulloblastoma exhibits marked intertumoural heterogeneity, with at least four distinct molecular variants, previous attempts to identify targets for therapy have been underpowered because of small samples sizes. Here we report somatic copy number aberrations (SCNAs) in 1,087 unique medulloblastomas. SCNAs are common in medulloblastoma, and are predominantly subgroup-enriched. The most common region of focal copy number gain is a tandem duplication of SNCAIP, a gene associated with Parkinson's disease, which is exquisitely restricted to Group 4α. Recurrent translocations of PVT1, including PVT1-MYC and PVT1-NDRG1, that arise through chromothripsis are restricted to Group 3. Numerous targetable SCNAs, including recurrent events targeting TGF-β signalling in Group 3, and NF-κB signalling in Group 4, suggest future avenues for rational, targeted therapy.


Document Type: Article in Press
Source: Scopus

 

Boyer, P.a , Lienard, P.b , Xu, J.c
Cultural differences in investing in others and in the future: Why measuring trust is not enough
(2012) PLoS ONE, 7 (7), art. no. e40750, .

a Departments of Psychology and Anthropology, Washington University in St. Louis, St. Louis, MO, United States
b Department of Anthropology, University of Nevada, Las Vegas, NV, United States
c Department of Anthropology, Washington University in St. Louis, St. Louis, MO, United States

Abstract
Standard measures of generalized trust in others are often taken to provide reliable indicators of economic attitudes in different countries. Here we compared three highly distinct groups, in Kenya, China and the US, in terms of more specific attitudes, [a] people's willingness to invest in the future, [b] their willingness to invest in others, and [c] their trust in institutions. Results suggest that these measures capture deep differences in economic attitudes that are not detected by standard measures of generalized trust. © 2012 Boyer et al.


Document Type: Article
Source: Scopus

 

Cho, Y., Cavalli, V.
HDAC5 is a novel injury-regulated tubulin deacetylase controlling axon regeneration
(2012) EMBO Journal, 31 (14), pp. 3063-3078. 


Department of Anatomy and Neurobiology, Washington University in St Louis, School of Medicine, 660 South Euclid Avenue, St Louis, MO 63110-1093, United States

Abstract
Axon regeneration is an essential process to rebuild functional connections between injured neurons and their targets. Regenerative axonal growth requires alterations in axonal microtubule dynamics, but the signalling mechanisms involved remain incompletely understood. Our results reveal that axon injury induces a gradient of tubulin deacetylation, which is required for axon regeneration both in vitro and in vivo. This injury-induced tubulin deacetylation is specific to peripheral neurons and fails to occur in central neurons. We found that tubulin deacetylation is initiated by calcium influx at the site of injury, and requires protein kinase C-mediated activation of the histone deacetylase 5 (HDAC5). Our findings identify HDAC5 as a novel injury-regulated tubulin deacetylase that plays an essential role in growth cone dynamics and axon regeneration. In addition, our results suggest a mechanism for the spatial control of tubulin modifications that is required for axon regeneration. © 2012 European Molecular Biology Organization | All Rights Reserved.


Author Keywords
axon regeneration;  calcium signalling;  histone deacetylase;  microtubule;  protein kinase C


Document Type: Article
Source: Scopus

 

Sanchez, C.E.a , Richards, J.E.a , Almli, C.R.b
Age-specific MRI templates for pediatric neuroimaging
(2012) Developmental Neuropsychology, 37 (5), pp. 379-399. 


a Department of Psychology, University of South Carolina, Columbia, SC 29208, United States
b Programs in Occupational Therapy and Neuroscience, Departments of Neurology and Psychology, Washington University School of Medicine, St. Louis, MI, United States

Abstract
This study created a database of pediatric age-specific magnetic resonance imaging (MRI) brain templates for normalization and segmentation. Participants included children from 4.5 through 19.5 years, totaling 823 scans from 494 subjects. Open-source processing programs (FMRIB Software Library, Statistical Parametric Mapping, Advanced Normalization Tools [ANTS]) constructed head, brain, and segmentation templates in 6-month intervals. The tissue classification (white matter [WM], gray matter [GM], cerebrospinal fluid) showed changes over age similar to previous reports. A volumetric analysis of age-related changes in WM and GM based on these templates showed expected increase/decrease pattern in GM and an increase in WM over the sampled ages. This database is available for use for neuroimaging studies (http://jerlab. psych.sc.edu/neurodevelopmentalmridatabase). © 2012 Copyright Taylor and Francis Group, LLC.


Document Type: Article
Source: Scopus

 

Chen, Y.a b , Klonowski, P.W.a c , Lind, A.C.a , Lu, D.a
Differentiating neurotized melanocytic nevi from neurofibromas using melan-A (MART-1) immunohistochemical stain
(2012) Archives of Pathology and Laboratory Medicine, 136 (7), pp. 810-815. 


a Department of Pathology and Immunology, Washington University School of Medicine, Campus Box 8118, 660 S Euclid Ave, St Louis, MO 63110, United States
b Department of Pathology, Community Hospital Anderson, Anderson, IN, United States
c Department of Pathology, University of Calgary and Calgary Laboratory Services, Calgary, AB, Canada

Abstract
Context. - Neurotized melanocytic nevi and neurofibromas are common, benign cutaneous neoplasms. Usually they are histologically distinct from each other; however, neurotized melanocytic nevi and neurofibromas can be clinically and histologically similar. Objective. - To determine whether Melan-A (MART-1) immunohistochemical stain is sufficient to differentiate neurotized melanocytic nevi from neurofibromas. Design. - Forty-nine consecutive specimens of melanocytic nevi with neurotization and 49 specimens of neurofibromas were selected. We used antibodies against Melan-A, S100, and neurofilament protein. Results. - All of the melanocytic nevi showed Melan-A staining within the neurotized areas, with most of the areas staining strongly positive, whereas all the neurofibromas were completely absent of Melan-A stain. All of the nevi, including the neurotized areas, stained strongly and diffusely for S100, whereas all the neurofibromas showed a distinctive, sharp, wavy pattern of S100 staining. Neurofilament protein showed scattered staining of both melanocytic nevi and neurofibromas. Conclusions. - Our data indicate that Melan-A immunohistochemical staining is helpful in differentiating neurotized melanocytic nevi from neurofibromas when distinction on histomorphology alone is difficult.


Document Type: Article
Source: Scopus

 

Peiniger, S.a b , Nienaber, U.b , Lefering, R.c , Braun, M.a , Wafaisade, A.a b , Borgman, M.A.b d , Spinella, P.C.e f g , Maegele, M.a b
Glasgow Coma Scale as a predictor for hemocoagulative disorders after blunt pediatric traumatic brain injury*
(2012) Pediatric Critical Care Medicine, 13 (4), pp. 455-460. 


a Department of Trauma and Orthopedic Surgery, University of Witten/Herdecke, Cologne-Merheim Medical Centre, Cologne, Germany
b Institute for Research in Operative Medicine, University of Witten/Herdecke, Cologne-Merheim Medical Centre, Cologne, Germany
c Institute for Research in Operative Medicine, University of Witten-Herdecke, Campus Cologne-Merheim, Koln, Germany
d Brooke Army Medical Center, Fort Sam Houston, Houston, TX, United States
e Department of Pediatrics, Washington University in St Louis, St. Louis, MO, United States
f Washington University in St Louis, St. Louis, MO, United States
g U.S. Army Institute of Surgical Research, Ft. Sam Houston, TX., United States

Abstract
OBJECTIVE: Coagulopathy is a complication of traumatic brain injury and its presence after injury has been identified as a risk factor for prognosis. It was our aim to determine whether neurologic findings reflected by Glasgow Coma Scale at initial resuscitation can predict hemocoagulative disorders resulting from traumatic brain injury that may aggravate clinical sequelae and outcome in children. DESIGN: A retrospective analysis of 200 datasets from children with blunt, isolated traumatic brain injury documented in the Trauma Registry of the Deutsche Gesellschaft für Unfallchirurgie was conducted. Inclusion criteria were primary admission, age <14 yrs, and sustained isolated blunt traumatic brain injury. SETTING: Trauma Registry of the Deutsche Gesellschaft für Unfallchirurgie-affiliated trauma centers in Germany. PATIENTS: Two hundred datasets of children (age <14 yrs) with blunt isolated traumatic brain injury were analyzed: children were subdivided into two groups according to Glasgow Coma Scale at the scene (Glasgow Coma Scale ≤8 vs. Glasgow Coma Scale >8) and reviewed for coagulation abnormalities upon emergency room admission and outcome. MEASUREMENT AND MAIN RESULTS: Fifty-one percent (n = 102 of 200) of children had Glasgow Coma Scale >8 and 49% (n = 98 of 200) had Glasgow Coma Scale ≤8 at the scene. The incidence of coagulopathy at admission was higher in children with Glasgow Coma Scale ≤8 compared to children with Glasgow Coma Scale >8: 44% (n = 31 of 71) vs. 14% (n = 11 of 79) (p < .001). Multivariate logistic regression revealed that Glasgow Coma Scale ≤8 at scene was associated with coagulopathy at admission (odds ratio 3.378, p = .009) and stepwise regression identified Glasgow Coma Scale ≤8 as an independent risk factor for coagulopathy. Mortality in children with Glasgow Coma Scale ≤8 at scene was substantially higher with the presence of coagulation abnormalities at admission compared to children in which coagulopathy was absent (51.6%, n = 16 of 31 vs. 5% n = 2 of 40). CONCLUSIONS: Glasgow Coma Scale ≤8 at scene in children with isolated traumatic brain injury is associated with increased risk for coagulopathy and mortality. These results may guide laboratory testing, management, and blood bank resources in acute pediatric trauma care. Copyright © 2012 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.


Author Keywords
Children;  Glasgow Coma Scale;  Hemocoagulative disorders;  Traumatic brain injury


Document Type: Article
Source: Scopus

 

High, K.P.a , Brennan-Ing, M.b , Clifford, D.B.c , Cohen, M.H.d , Currier, J.e , Deeks, S.G.f , Deren, S.g , Effros, R.B.e , Gebo, K.h , Goronzy, J.J.i , Justice, A.C.j , Landay, A.k , Levin, J.l , Miotti, P.G.m , Munk, R.J.n , Nass, H.o , Rinaldo, C.R.p , Shlipak, M.G.q , Tracy, R.r , Valcour, V.s , Vance, D.E.t , Walston, J.D.u , Volberding, P.v
HIV and aging: State of knowledge and areas of critical need for research. a report to the NIH office of AIDS research by the HIV and aging working group
(2012) Journal of Acquired Immune Deficiency Syndromes, 60 (SUPPL.1), pp. S1-S18. 


a Department of Internal Medicine, Section on Infectious Diseases, Wake Forest University Baptist Medical Center, Winston Salem, NC, United States
b ACRIA Center on HIV and Aging, New York, NY, United States
c Department of Neurology, Washington University School of Medicine, Saint Louis, MO, United States
d Department of Internal Medicine, Rush University, Women Interagency HIV Study (WIHS), Chicago, IL, United States
e Department of Medicine, Department of Pathology and Laboratory Medicine, University of California, Los Angeles, Los Angeles, CA, United States
f Department of Medicine, University of California, San Francisco, San Francisco, CA, United States
g New York University College of Nursing, New York, NY, United States
h Department of Medicine, Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, MD, United States
i Department of Immunology and Rheumatology, Stanford University School of Medicine, Stanford, CA, United States
j Department of Medicine, Yale University, Veteran Affairs Connecticut Healthcare System, West Haven, CT, United States
k Department of Immunology and Microbiology, Rush University Medical Center, Chicago, IL, United States
l Office of AIDS Research National AIDS Treatment Advocacy Project, New York, NY, United States
m Office of AIDS Research National Institutes of Health, DHHS, Rockville, MD, United States
n AIDS InfoNet, Arroyo Seco, NM, United States
p Department of Infectious Diseases and Microbiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, United States
q Department of Medicine, Veteran Affairs Medical Center, University of California, San Francisco, San Francisco, CA, United States
r Department of Pathology and Biochemistry, University of Vermont College of Medicine, Colchester, VT, United States
s Division of Geriatric Medicine, Department of Neurology, University of California, San Francisco, San Francisco, CA, United States
t School of Nursing, University of Alabama at Birmingham, Birmingham, AL, United States
u Department of Medicine, San Francisco Veterans Affairs Medical Center, University of California, San Francisco, San Francisco, CA, United States
v Division of Geriatric Medicine and Gerontology, Johns Hopkins University School of Medicine, Baltimore, MD, United States

Abstract
HIV risk behaviors, susceptibility to HIV acquisition, progression of disease after infection, and response to antiretroviral therapy all vary by age. In those living with HIV, current effective treatment has increased the median life expectancy to >70 years of age. Biologic, medical, individual, social, and societal issues change as one ages with HIV infection, but there has been only a small amount of research in this field. Therefore, the Office of AIDS Research of the National Institutes of Health commissioned a working group to develop an outline of the current state of knowledge and areas of critical need for research in HIV and Aging; the working groups' findings and recommendations are summarized in this report. Key overarching themes identified by the group included the following: multimorbidity, polypharmacy, and the need to emphasize maintenance of function; the complexity of assessing HIV versus treatment effects versus aging versus concurrent disease; the inter-related mechanisms of immune senescence, inflammation, and hypercoagulability; the utility of multivariable indices for predicting outcomes; a need to emphasize human studies to account for complexity; and a required focus on issues of community support, caregivers, and systems infrastructure. Critical resources are needed to enact this research agenda and include expanded review panel expertise in aging, functional measures, and multimorbidity, and facilitated use and continued funding to allow long-term follow-up of cohorts aging with HIV. © 2012 by Lippincott Williams & Wilkins.


Author Keywords
aging;  co-morbidity;  HIV/AIDS;  research priorities


Document Type: Article
Source: Scopus

 

Ances, B.a b
The more things change the more they stay the same: A case report of neurology residency experiences
(2012) Journal of Neurology, 259 (7), pp. 1321-1325. 

a Department of Neurology, Washington University School of Medicine, Box 8111, 660 South Euclid, St. Louis, MO 63110, United States
b Department of Biomedical Engineering, Washington University, School of Medicine, St. Louis, MO, United States

Abstract
This study compared the neurology residency training experience for a single neurology resident at the University of Pennsylvania from the years 2002-2005. The prevalence of encounters seen during this residency was compared to the prevalence of neurological disorders typically observed by ambulatory neurologists in the United States (US). A total of 1, 333 patients were evaluated during this residency. Ischemic stroke/transient ischemic accident, epilepsy, metabolic encephalopathy, peripheral neuropathy, and multiple sclerosis were the most common neurological disorders observed. The four most common reasons for an outpatient visit to a neurologist (i.e., headache/ migraine, epilepsy, cerebrovascular disease, and peripheral neuropathy) typically account for approximately 49-55% of all appointments, but only contributed to approximately 40% of patient encounters during this neurology residency. While these results reflect the encounters of a single neurology resident, both the total number and distribution of neurological diagnoses were similar to previous experiences over two decades ago at US academic medical centers despite significant changes in health care delivery and policy. This case report demonstrates that neurology residency programs continue to overemphasize acute management of inpatient neurological disorders compared to outpatient care of more prevalent neurological complaints. Additional measures could be instituted to ensure a broader range of experiences during residency (i.e., online resident log). These methods could allow residency coordinators to identify certain areas of deficiency with regards to exposure to patients for a resident and ensure greater competency during residency. © Springer-Verlag 2011.


Author Keywords
Education;  Residency


Document Type: Article
Source: Scopus

 

Leuthardt, E.C.a b h , Pei, X.-M.c , Breshears, J.b , Gaona, C.a , Sharma, M.a , Freudenberg, Z.g , Barbour, D.a , Schalk, G.b c d e f
Temporal evolution of gamma activity in human cortex during an overt and covert word repetition task
(2012) Frontiers in Human Neuroscience, (MAY 2012), art. no. 99, . 


a Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, MO, United States
b Department of Neurosurgery, School of Medicine, Washington University in St. Louis, St. Louis, MO, United States
c Brain-Computer Interface R and D Program, Wadsworth Center, New York State Department of Health, Albany, NY, United States
d Department of Neurology, Albany Medical College, Albany, NY, United States
e Department of Biomedical Engineering, Rensselaer Polytechnic Institute, Troy, NY, United States
f Department of Biomedical Sciences, State University of New York, Albany, NY, United States
g Department of Computer Science, Washington University in St. Louis, St. Louis, MO, United States
h Center for Innovation in Neuroscience and Technology, Washington University in St. Louis, St. Louis, MO, United States

Abstract
Several scientists have proposed different models for cortical processing of speech. Classically, the regions participating in language were thought to be modular with a linear sequence of activations. More recently, modern theoretical models have posited a more hierarchical and distributed interaction of anatomic areas for the various stages of speech processing. Traditional imaging techniques can only define the location or time of cortical activation, which impedes the further evaluation and refinement of these models. In this study, we take advantage of recordings from the surface of the brain [electrocorticography (ECoG)], which can accurately detect the location and timing of cortical activations, to study the time course of ECoG high gamma (HG) modulations during an overt and covert word repetition task for different cortical areas. For overt word production, our results show substantial perisylvian cortical activations early in the perceptual phase of the task that were maintained through word articulation. However, this broad activation is attenuated during the expressive phase of covert word repetition. Across the different repetition tasks, the utilization of the different cortical sites within the perisylvian region varied in the degree of activation dependent on which stimulus was provided (auditory or visual cue) and whether the word was to be spoken or imagined. Taken together, the data support current models of speech that have been previously described with functional imaging. Moreover, this study demonstrates that the broad perisylvian speech network activates early and maintains suprathreshold activation throughout the word repetition task that appears to be modulated by the demands of different conditions. © 2012 Leuthardt, Pei, Breshears, Gaona, Sharma, Freudenberg, Barbour and Schalk.


Author Keywords
Cortex;  Electrocorticography;  Gamma rhythms;  Human;  Speech


Document Type: Article
Source: Scopus

 

August 1, 2012

Cheon, Y.a , Kim, H.-W.a , Igarashi, M.a , Modi, H.R.a , Chang, L.a , Ma, K.a , Greenstein, D.b , Wohltmann, M.c , Turk, J.c , Rapoport, S.I.a , Taha, A.Y.a
Disturbed brain phospholipid and docosahexaenoic acid metabolism in calcium-independent phospholipase A 2-VIA (iPLA 2β)- knockout mice
(2012) Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids, 1821 (9), pp. 1278-1286. 


a Brain Physiology and Metabolism Section, National Institute on Aging, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892, United States
b Child Psychiatry Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892, United States
c Medicine Department, Mass Spectrometry Facility, Washington University School of Medicine, St. Louis, MO 63110, United States

Abstract
Calcium-independent phospholipase A 2 group VIA (iPLA 2β) releases docosahexaenoic acid (DHA) from phospholipids in vitro. Mutations in the iPLA 2β gene, PLA2G6, are associated with dystonia-parkinsonism and infantile neuroaxonal dystrophy. To understand the role of iPLA 2β in brain, we applied our in vivo kinetic method using radiolabeled DHA in 4 to 5-month-old wild type (iPLA 2β +/+) and knockout (iPLA 2β -/-) mice, and measured brain DHA kinetics, lipid concentrations, and expression of PLA 2, cyclooxygenase (COX), and lipoxygenase (LOX) enzymes. Compared to iPLA 2β +/+ mice, iPLA 2β -/- mice showed decreased rates of incorporation of unesterified DHA from plasma into brain phospholipids, reduced concentrations of several fatty acids (including DHA) esterified in ethanolamine- and serine-glycerophospholipids, and increased lysophospholipid fatty acid concentrations. DHA turnover in brain phospholipids did not differ between genotypes. In iPLA 2β -/- mice, brain levels of iPLA 2β mRNA, protein, and activity were decreased, as was the iPLA 2γ (Group VIB PLA 2) mRNA level, while levels of secretory sPLA 2-V mRNA, protein, and activity and cytosolic cPLA 2-IVA mRNA were increased. Levels of COX-1 protein were decreased in brain, while COX-2 protein and mRNA were increased. Levels of 5-, 12-, and 15-LOX proteins did not differ significantly between genotypes. Thus, a genetic iPLA 2β deficiency in mice is associated with reduced DHA metabolism, profound changes in lipid-metabolizing enzyme expression (demonstrating lack of redundancy) and of phospholipid fatty acid content of brain (particularly of DHA), which may be relevant to neurologic abnormalities in humans with PLA2G6 mutations. © 2012 Elsevier B.V. All rights reserved.

Author Keywords
DHA;  Incorporation;  Lipid;  Mouse;  PLA2G6;  Turnover


Document Type: Article
Source: Scopus

 

Du, F.a , Abrams, R.A.b
Out of control: Attentional selection for orientation is thwarted by properties of the underlying neural mechanisms
(2012) Cognition, 124 (3), pp. 361-366. 


a State Key Laboratory of Brain and Cognitive Science, Institute of Psychology, Chinese Academy of Sciences, Beijing 100101, China
b Washington University, St. Louis, MO 63130, United States

Abstract
To avoid sensory overload, people are able to selectively attend to a particular color or direction of motion while ignoring irrelevant stimuli that differ from the desired one. We show here for the first time that it is also possible to selectively attend to a specific line orientation-but with an important caveat: orientations that are perpendicular to the target orientation cannot be suppressed. This effect reflects properties of the neural mechanisms selective for orientation and reveals the extent to which contingent capture is constrained not only by one's top-down goals but also by feature preferences of visual neurons. © 2012 Elsevier B.V.


Author Keywords
Attention;  Contingent capture;  Orientation-based selection;  Top-down control


Document Type: Article
Source: Scopus

 

Eaton, M.M., Lim, Y.B., Bracamontes, J., Steinbach, J.H., Akk, G.
Agonist-specific conformational changes in the α1-γ2 subunit interface of the GABA A receptor
(2012) Molecular Pharmacology, 82 (2), pp. 255-263. 


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

Abstract
The GABA A receptor undergoes conformational changes upon the binding of agonist that lead to the opening of the channel gate and a flow of small anions across the cell membrane. Besides the transmitter GABA, allosteric ligands such as the general anesthetics pentobarbital and etomidate can activate the receptor. Here, we have investigated the agonist specificity of structural changes in the extracellular domain of the receptor. We used the substituted cysteine accessibility method and focused on the γ2(S195C) site (loop F). We show that modification of the site with (2-sulfonatoethyl) methanethiosulfonate (MTSES) results in an enhanced response to GABA, indicating accessibility of the resting receptor to the modifying agent. Coapplication of GABA or muscimol, but not of gabazine, with MTSES prevented the effect, suggesting that GABA and muscimol elicit a conformational change that reduces access to the γ2(S195C) site. Exposure of the receptors to MTSES in the presence of the allosteric activators pentobarbital and etomidate resulted in an enhanced current response indicating accessibility and labeling of the γ2(S195C) site. However, comparison of the rates of modification indicated that labeling in the presence of etomidate was significantly faster than that in the presence of pentobarbital or gabazine or in resting receptors. We infer from the data that the structure of the α1-γ2 subunit interface undergoes agonist-specific conformational changes. Copyright © 2012 The American Society for Pharmacology and Experimental Therapeutics.


Document Type: Article
Source: Scopus

 

Wang, K.-S.a , Liu, X.a , Zhang, Q.b , Zeng, M.a
ANAPC1 and SLCO3A1 are associated with nicotine dependence: Meta-analysis of genome-wide association studies
(2012) Drug and Alcohol Dependence, 124 (3), pp. 325-332. 


a Department of Biostatistics and Epidemiology, College of Public Health, East Tennessee State University, Johnson City, TN 37614, United States
b Division of Statistical Genomics, Washington University School of Medicine, St. Louis, MO 63108, United States

Abstract
Twin and family studies have shown that there is substantial evidence for a genetic component in the vulnerability to nicotine dependence (ND). The purpose of this study was to perform a meta-analysis on two genome-wide association (GWA) data involving 1079 cases of ND and 1341 controls in Caucasian populations. Through meta-analysis we identified 50 SNPs associated with ND with p&lt;10 -4. The best associated SNP rs7163369 (p=3.27×10 -6) was located at 15q26 within SLCO3A1 gene while the second best SNP was rs9308631 (p=9.06×10 -6) at 2q12.1 near ANAPC1. The third interesting locus rs688011 (p=1.08×10 -5) was at 11q23.2 intergenic between NCAM1 and TCC12. Through meta-analysis, we found two additional ND associated genes ZCCHC14 (the top SNP was rs13334632, p=1.28×10 -5) and KANK1 (the top SNP was rs13286166, p=1.49×10 -5). The first top SNP rs7163369 within SLCO3A1 in the meta-analysis was replicated in the Australian twin-family study of 778 families (p=6.11×10 -5) while SNP rs9653414 within ANAPC1 (p=4.61×10 -5) in the meta-analysis was replicated in the family sample (p=9.31×10 -4). Furthermore, rs2241617 in ZCCHC14 and rs4742225 in KANK1 showed strong associations with ND (p=1.06×10 -7 and 4.81×10 -7, respectively) in the replication sample. In addition, several SNPs of these loci (ANAPC1, KANK1, NACM1, TCC12, SLCO3A1 and ZCCHC14) were associated with alcohol dependence. In conclusion, we identified several loci associated with ND through meta-analysis of two GWA studies. These findings offer the potential for new insights into the pathogenesis of ND. © 2012.


Author Keywords
ANAPC1;  Genome-wide association;  Meta-analysis;  Nicotine dependence;  SLCO3A1


Document Type: Article
Source: Scopus

 

Halpin, C.a b , Shi, H.c , Reda, D.c , Antonelli, P.J.d , Babu, S.e , Carey, J.P.f , Gantz, B.J.g , Goebel, J.A.h , Hammerschlag, P.E.i , Harris, J.P.j , Isaacson, B.k , Lee, D.b , Linstrom, C.J.l , Parnes, L.S.m , Slattery, W.H.n , Telian, S.A.o , Vrabec, J.T.p , Rauch, S.b
Audiology in the sudden hearing loss clinical trial
(2012) Otology and Neurotology, 33 (6), pp. 907-911. 


a Department of Audiology, Massachusetts Eye and Ear Infirmary, 243 Charles Street, Boston, MA 02114, United States
b Department of Otology and Laryngology, Harvard Medical School, Boston, MA, United States
c Hines Cooperative Studies Coordinating Center, Hines, IL, United States
d Department of Otolaryngology, University of Florida, Gainesville, FL, United States
e Department of Otology/Skull Base Surgery, Michigan Ear Institute, Farmington Hills, MI, United States
f Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University, School of Medicine, Baltimore, MD, United States
g Department of Otolaryngology-Head and Neck Surgery, University of Iowa Hospitals and Clinics, Iowa City, IA, United States
h Department of Otolaryngology, Washington University, School of Medicine, St. Louis, MO, United States
i Department of Otolaryngology, New York University, School of Medicine, New York, NY, United States
j Division of Otolaryngology-Head and Neck Surgery, University of California San Diego Medical Center, San Diego, CA, United States
k Department of Otolaryngology-Head and Neck Surgery, University of Texas Southwestern Medical Center at Dallas, Dallas, TX, United States
l Department of Otolaryngology-Head and Neck Surgery, New York Eye and Ear Infirmary, New York, NY, United States
m Department of Otolaryngology, London Health Sciences Centre Research Inc., London, ON, United States
n Clinical Studies, House Ear Institute, University of Southern California, Los Angeles, CA, United States
o Department of Otolaryngology, University of Michigan, Ann Arbor, MI, United States
p Department of Otolaryngology-Head and Neck Surgery, Baylor College of Medicine, Houston, TX, United States

Abstract
Objective: To report the pretreatment and posttreatment population characteristics and the overall stability of the audiologic outcomes found during the Sudden Hearing Loss Clinical Trial (ClinicalTrials.gov: Identifier NCT00097448). Study Design: Multicenter, prospective randomized noninferiority trial of oral versus intratympanic (IT) steroid treatment of sudden sensorineural hearing loss (SSNHL). Setting: Fifteen academically based otology practices. Patients: Two hundred fifty patients with unilateral SSNHL presenting within 14 days of onset with 50 dBHL or greater pure tone average hearing threshold in the affected ear. Intervention: Either 60 mg/d oral prednisone for 14 days with a 5-day taper (121 patients) or 4 IT doses for 14 days of 40 mg/ml methylprednisolone (129 patients). Main Outcome Measure: Primary end point was change in hearing [dB PTA] at 2 months after treatment. Noninferiority was defined as less than 10 dB difference in hearing outcome between treatments. In this article, pretreatment and posttreatment hearing findings will be reported in detail. Results: A general (and stable) effect of treatment and a specific effect of greater improvement at low frequencies were found in both treatment groups. Conclusion: Hearing improvements are stable, and a significantly greater improvement occurs with lower frequency after either oral or IT steroid treatment of SSNHL. © 2012, Otology & Neurotology, Inc.


Author Keywords
Audiometry;  Sudden hearing loss;  Word recognition


Document Type: Article
Source: Scopus

 

Zenga, J.a , Gagnon, P.M.a , Vogel, J.b , Chole, R.A.a
Biofilm formation by otopathogenic strains of Pseudomonas aeruginosa is not consistently inhibited by ethylenediaminetetraacetic acid
(2012) Otology and Neurotology, 33 (6), pp. 1007-1012. 


a Department of Otolaryngology, Washington University, St. Louis, MO, United States
b Department of Molecular Microbiology, Washington University, St. Louis, MO, United States

Abstract
Hypothesis: Biofilm formation in otopathogenic of Pseudomonas aeruginosa (OPPA) strains is inhibited by ethylenediaminetetraacetic acid (EDTA). Background: EDTA, a widely used chelating agent, has been shown to inhibit biofilm formation in a number of bacteria. Because EDTA may be a well-tolerated reagent to inhibit biofilm formation in cases of suppurative otitis media, we asked if it might be effective in all OPPA strains isolated from chronically infected cholesteatomas. Methods: OPPA strains were isolated from patients with infected cholesteatomas. These strains were grown into log phase then were placed in minimal media with varying concentrations of EDTA and incubated for varying periods. Biofilm production was measured colorimetrically by staining with crystal violet. Results: Without added EDTA, most otopathogenic PA exhibited a distinct, but varying, time course of biofilm formation and dissolution with peak production at 12 to 18 hours. Addition of 1 mM EDTA resulted in a delay in the time to peak biofilm formation for most strains, although the amount of biofilm was not decreased. In contrast, some strains showed greater biofilm production with 1 mM EDTA compared with the untreated bacteria. Addition of 10 mM EDTA resulted in a similar effect. Some strains increased biofilm production over controls. Moreover, EDTA inhibited planktonic growth of all OPPA strains at the concentrations studied. Conclusion: Our hypothesis was disproven: EDTA tends to delay biofilm development, although it consistently inhibits planktonic growth. Because EDTA does not cause suppression of biofilm production in all isolates of OPPA, usefulness as an antimicrobial is questioned. © 2012, Otology & Neurotology, Inc.


Author Keywords
Biofilm;  Cholesteatoma;  Ethylenediaminetetraacetic acid;  Pseudomonas aeruginosa


Document Type: Article
Source: Scopus

 

Stein, P.K.a , Soare, A.b c , Meyer, T.E.b , Cangemi, R.b d , Holloszy, J.O.b , Fontana, L.b e f
Caloric restriction may reverse age-related autonomic decline in humans
(2012) Aging Cell, 11 (4), pp. 644-650. 


a HRV Laboratory, Washington University School of Medicine, 660 S. Euclid Avenue, Campus Box 8086, St. Louis, MO, 63110, United States
b Division of Geriatrics and Nutritional Science, Washington University School of Medicine, St. Louis, MO, United States
c Department of Endocrinology and Diabetes, University Campus Bio-Medico, Rome, Italy
d Department of Experimental Medicine, University of Rome 'La Sapienza', Rome, Italy
e Department of Medicine, Salerno University School of Medicine, Salerno, Italy
f CEINGE Biotecnologie Avanzate, Napoli, Italy

Abstract
Caloric restriction (CR) retards aging in laboratory rodents. No information is available on the effects of long-term CR on physiologic markers of aging and longevity in humans. Heart rate variability (HRV) is a marker for cardiac autonomic functioning. The progressive decline in HRV with aging and the association of higher HRV with better health outcomes are well established. Heart rate variability assessment is a reliable tool by which the effects of CR on autonomic function can be assessed. Time- and frequency-domain analyses compared 24-h HRV in 22 CR individuals aged 35-82years and 20 age-matched controls eating Western diets (WD). The CR group was significantly leaner than the WD group. Heart rate was significantly lower, and virtually, all HRV values were significantly higher in the CR group than in the WD group (P<0.002). Heart rate variability in the CR individuals was comparable with published norms for healthy individuals 20years younger. In addition, when differences in heart rate (HR) and HRV between CR and WD were compared with previously published changes in HRV induced in healthy adults given atenolol, percent differences in each measure were generally similar in direction and magnitude and suggested declines in sympathetic and increases in parasympathetic modulation of HR and increased circadian variability associated with CR. These findings provide evidence that CR has direct systemic effects that counter the expected age-associated changes in autonomic function so that HRV indexes in CR individuals are similar to those of individuals 20years younger eating WDs. © 2012 The Authors. Aging Cell © 2012 Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland.


Author Keywords
Aging;  Autonomic function;  Calorie restriction;  Cardiovascular health;  Heart rate variability;  Parasympathetic function


Document Type: Article
Source: Scopus

 

Nothdurft, R., Sarder, P., Bloch, S., Culver, J., Achilefu, S.
Fluorescence lifetime imaging microscopy using near-infrared contrast agents
(2012) Journal of Microscopy, 247 (2), pp. 202-207. 

Washington University, School of Medicine, Department of Radiology, Scott Avenue, St. Louis, MO, United States

Abstract
Although single-photon fluorescence lifetime imaging microscopy (FLIM) is widely used to image molecular processes using a wide range of excitation wavelengths, the captured emission of this technique is confined to the visible spectrum. Here, we explore the feasibility of utilizing near-infrared (NIR) fluorescent molecular probes with emission >700 nm for FLIM of live cells. The confocal microscope is equipped with a 785 nm laser diode, a red-enhanced photomultiplier tube, and a time-correlated single photon counting card. We demonstrate that our system reports the lifetime distributions of NIR fluorescent dyes, cypate and DTTCI, in cells. In cells labelled separately or jointly with these dyes, NIR FLIM successfully distinguishes their lifetimes, providing a method to sort different cell populations. In addition, lifetime distributions of cells co-incubated with these dyes allow estimate of the dyes' relative concentrations in complex cellular microenvironments. With the heightened interest in fluorescence lifetime-based small animal imaging using NIR fluorophores, this technique further serves as a bridge between in vitro spectroscopic characterization of new fluorophore lifetimes and in vivo tissue imaging. © 2012 Royal Microscopical Society.


Author Keywords
Fluorescence lifetime imaging microscopy;  Live cell imaging;  Near infrared fluorescent molecular probes


Document Type: Article
Source: Scopus

 

Nelson, S.M.a , McDermott, K.B.a b , Petersen, S.E.a b c d e
In favor of a 'fractionation' view of ventral parietal cortex: Comment on Cabeza et al
(2012) Trends in Cognitive Sciences, 16 (8), pp. 399-400.

a Department of Psychology, Washington University in St. Louis, St. Louis, MO 63130, United States
b Department of Radiology, Washington University in St. Louis, St. Louis, MO 63110, United States
c Department of Neurology, Washington University in St. Louis, St. Louis, MO 63110, United States
d Department of Anatomy and Neurobiology, Washington University in St. Louis, St. Louis, MO 63110, United States
e Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, MO 63130, United States

Document Type: Letter
Source: Scopus

 

Yao, J., Maslov, K.I., Wang, L.V.
In vivo photoacoustic tomography of total blood flow and potential imaging of cancer angiogenesis and hypermetabolism
(2012) Technology in Cancer Research and Treatment, 11 (4), pp. 301-307. 


Optical Imaging Laboratory, Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, MO 63130, United States

Abstract
Blood flow is a key parameter in studying cancer angiogenesis and hypermetabolism. Current photoacoustic blood flow estimation methods focus on either the axial or transverse component of the flow vector. However, the Doppler angle (beam-to-flow angle) is needed to calculate the total flow speed, and it cannot always be estimated accurately in practice, especially when the system's axial and lateral resolutions are different. To overcome this problem, we propose a method to compute the total flow speed and Doppler angle by combining the axial and transverse flow measurements. The method has been verified by flowing bovine blood in a plastic tube at various speeds and Doppler angles. The error was experimentally determined to be less than 0.3 mm/s for total flow speed, and less than 158 for the Doppler angle. In addition, the method was tested in vivo on a mouse ear. We believe that the proposed method has the potential to be used for cancer angiogenesis and hypermetabolism imaging. ©Adenine Press (2012).


Author Keywords
Axial flow;  Doppler angle;  Photoacoustic microscopy;  Total blood flow velocity;  Transverse flow


Document Type: Article
Source: Scopus

 

Lyons-Warren, A.M., Hollmann, M., Carlson, B.A.
Sensory receptor diversity establishes a peripheral population code for stimulus duration at low intensities
(2012) Journal of Experimental Biology, 215 (15), pp. 2586-2600. 


Department of Biology, Washington University in St Louis, Campus Box 1137, One Brookings Drive, St Louis, MO 63130-4899, United States

Abstract
Peripheral filtering is a fundamental mechanism for establishing frequency tuning in sensory systems. By contrast, detection of temporal features, such as duration, is generally thought to result from temporal coding in the periphery, followed by an analysis of peripheral response times within the central nervous system. We investigated how peripheral filtering properties affect the coding of stimulus duration in the electrosensory system of mormyrid fishes using behavioral and electrophysiological measures of duration tuning. We recorded from individual knollenorgans, the electrosensory receptors that mediate communication, and found correlated variation in frequency tuning and duration tuning, as predicted by a simple circuit model. In response to relatively high intensity stimuli, knollenorgans responded reliably with fixed latency spikes, consistent with a temporal code for stimulus duration. At near-threshold intensities, however, both the reliability and the temporal precision of responses decreased. Evoked potential recordings from the midbrain, as well as behavioral responses to electrosensory stimulation, revealed changes in sensitivity across the range of durations associated with the greatest variability in receptor sensitivity. Further, this range overlapped with the natural range of variation in species-specific communication signals, suggesting that peripheral duration tuning affects the coding of behaviorally relevant stimuli. We measured knollenorgan, midbrain and behavioral responses to natural communication signals and found that each of them were duration dependent. We conclude that at relatively low intensities for which temporal coding is ineffective, diversity among sensory receptors establishes a population code, in which duration is reflected in the population of responding knollenorgans. © 2012. Published by The Company of Biologists Ltd.


Author Keywords
Duration tuning;  Electroreception;  Mormyrid;  Peripheral filtering;  Sensory processing;  Temporal coding;  Weakly electric fish


Document Type: Article
Source: Scopus

 

Yu, L.a , Cui, J.a , Padakanti, P.K.a , Engel, L.b , Bagchi, D.P.b , Kotzbauer, P.T.b , Tu, Z.a
Synthesis and in vitro evaluation of α-synuclein ligands
(2012) Bioorganic and Medicinal Chemistry, 20 (15), pp. 4625-4634. 


a Department of Radiology, Washington University, School of Medicine, 510 South Kingshighway Boulevard, St. Louis, MO 63110, United States
b Department of Neurology, Washington University, School of Medicine, 660 S. Euclid Ave., St. Louis, MO 63110, United States

Abstract
Accumulation of misfolded α-synuclein in Lewy bodies and Lewy neurites is the pathological hallmark of Parkinson's disease (PD). To identify ligands having high binding potency toward aggregated α-synuclein, we synthesized a series of phenothiazine derivatives and assessed their binding affinity to recombinant α-synuclein fibrils using a fluorescent thioflavin T competition assay. Among 16 new analogues, the in vitro data suggest that compound 11b has high affinity to α-synuclein fibrils (K i = 32.10 ± 1.25 nM) and compounds 11d, 16a and16b have moderate affinity to α-synuclein fibrils (K i ≈ 50-100 nM). Further optimization of the structure of these analogues may yield compounds with high affinity and selectivity for aggregated α-synuclein. © 2012 Elsevier Ltd. All rights reserved.


Author Keywords
α-Synuclein;  Fluorescence;  Lewy bodies;  Parkinson's disease;  Phenothiazine


Document Type: Article
Source: Scopus

 

Chassin, L.a , Lee, M.R.a , Cho, Y.I.a , Wang, F.L.a , Agrawal, A.b , Sher, K.J.c , Lynskey, M.T.b
Testing multiple levels of influence in the intergenerational transmission of alcohol disorders from a developmental perspective: The example of alcohol use promoting peers and μ-opioid receptor M1 variation
(2012) Development and Psychopathology, 24 (3), pp. 953-967. 


a Psychology Department, Box 871104, Arizona State University, Tempe, AZ 85287-1104, United States
b Washington University School of Medicine, United States
c University of Missouri-Columbia, United States

Abstract
This study examined the interplay between the influence of peers who promote alcohol use and 1/4-opioid receptor M1 (OPRM1) genetic variation in the intergenerational transmission of alcohol use disorder (AUD) symptoms while separating the traitlike components of AUD symptoms from their age-specific manifestations at three ages from emerging adulthood (17-23 years) to adulthood (29-40 years). The results for males were consistent with genetically influenced peer selection mechanisms as mediators of parent alcoholism effects. Male children of alcoholics were less likely to be carriers of the G allele in single nucleotide polymorphism A118G (rs1799971), and those who were homozygous for the A allele were more likely to affiliate with alcohol use promoting peers who increased the risk for AUD symptoms at all ages. There was evidence for women of an interaction between OPRM1 variation and peer affiliations but only at the earliest age band. Peer influences had stronger effects among women who were G-carriers. These results illustrate the complex ways in which the interplay between influences at multiple levels of analysis can underlie the intergenerational transmission of alcohol disorders as well as the importance of considering age and gender differences in these pathways. © Copyright Cambridge University Press 2012.


Document Type: Article
Source: Scopus

 

Li, L.a , Rilling, J.K.b c d e , Preuss, T.M.b f g , Glasser, M.F.d h , Hu, X.a
The effects of connection reconstruction method on the interregional connectivity of brain networks via diffusion tractography
(2012) Human Brain Mapping, 33 (8), pp. 1894-1913. 


a Biomedical Imaging Technology Center, School of Medicine, Emory University, Atlanta, GA, United States
b Center for Translational and Social Neuroscience, Emory University, Atlanta, GA, United States
c Division of Psychobiology, Yerkes National Primate Research Center, Atlanta, GA, United States
d Department of Anthropology, Emory University, Atlanta, GA, United States
e Department of Psychiatry and Behavioral Sciences, Emory University, Atlanta, GA, United States
f Division of Neuropharmacology and Neurodegenerative Diseases, Yerkes National Primate Research Center, Atlanta, GA, United States
g Department of Pathology, School of Medicine, Emory University, Atlanta, GA, United States
h Department of Anatomy and Neurobiology, Washington University, St Louis, MO, United States

Abstract
Estimating the interregional structural connections of the brain via diffusion tractography is a complex procedure and the parameters chosen can affect the outcome of the connectivity matrix. Here, we investigated the influence of different connection reconstruction methods on brain connectivity networks. Specifically, we applied three connection reconstruction methods to the same set of diffusion MRI data, initiating tracking from deep white matter (method #1, M1), from the gray matter/white matter interface (M2), and from the gray/white matter interface with thresholded tract volume rather than the connection probability as the connectivity index (M3). Small-world properties, hub identification, and hemispheric asymmetry in connectivity patterns were then calculated and compared across methods. Despite moderate to high correlations in the graph-theoretic measures across different methods, significant differences were observed in small-world indices, identified hubs, and hemispheric asymmetries, highlighting the importance of reconstruction method on network parameters. Consistent with the prior reports, the left precuneus was identified as a hub region in all three methods, suggesting it has a prominent role in brain networks. © 2011 Wiley Periodicals, Inc.


Author Keywords
Connectivity;  Diffusion;  Macaque;  Modularity;  Network;  Probabilistic;  Small world;  Tractography


Document Type: Article
Source: Scopus

 

Hunter, J.M.a , Cirrito, J.R.b , Restivo, J.L.b , Kinley, R.D.a , Sullivan, P.M.c , Holtzman, D.M.b , Koger, D.a , Delong, C.a , Lin, S.a , Zhao, L.a , Liu, F.a , Bales, K.a , Paul, S.M.d
Emergence of a seizure phenotype in aged apolipoprotein epsilon 4 targeted replacement mice
(2012) Brain Research, 1467, pp. 120-132. 


a Neuroscience Discovery, Eli Lilly and Co., Indianapolis, IN 46285, United States
b Neurology, Knight Alzheimer's Disease Research Center, Washington University, St. Louis, MO 63110, United States
c Division of Geriatrics, Durham VA Medical Center, Duke University, Durham, NC 27710, United States
d Helen and Robert Appel Alzheimer's Disease Research Institute, Weill Cornell Medical College, Cornell University, 1300 York Avenue, New York, NY 10065, United States

Abstract
The apolipoprotein ε4 allele is the strongest genetic risk factor for late-onset Alzheimer's disease (AD) and is associated with earlier age of onset. The incidence of spontaneous seizures has been reported to be increased in sporadic AD as well as in the early onset autosomal dominant forms of AD. We now report the emergence of a seizure phenotype in aged apolipoprotein E4 (apoE4) targeted replacement (TR) mice but not in age-matched apoE2 TR or apoE3 TR mice. Tonic-clonic seizures developed spontaneously after 5 months of age in apoE4 TR mice and are triggered by mild stress. Female mice had increased seizure penetrance compared to male mice, but had slightly reduced overall seizure severity. The majority of seizures were characterized by head and neck jerks, but 25% of aged apoE4 TR mice had more severe tonic-clonic seizures which occasionally progressed to tonic extension and death. Aged apoE4 TR mice progressed through pentylenetetrazol-induced seizure stages more rapidly than did apoE3 TR and apoE2 TR mice. Electroencephalographic (EEG) recordings revealed more frequent bursts of synchronous theta activity in the hippocampus of apoE4 TR mice than in apoE2 TR or apoE3 TR mice. Cortical EEG recordings also revealed sharp spikes and other abnormalities in apoE4 TR mice. Taken together, these findings demonstrate the emergence of an age-dependent seizure phenotype in old apoE4 TR mice in the absence of human amyloid-β peptide (Aβ) overexpression, suggesting increased central nervous system neural network excitability. © 2012 Elsevier B.V.


Author Keywords
Alzheimer;  Amyloid beta;  Apolipoprotein E;  Epilepsy;  Seizure


Document Type: Article
Source: Scopus

 

Power, J.D.a , Barnes, K.A.a , Snyder, A.Z.a b , Schlaggar, B.L.a b c d , Petersen, S.E.a b d e
Corrigendum to "Spurious but systematic correlations in functional connectivity MRI networks arise from subject motion" [NeuroImage 59 (3) (2012) 2142-2154] (DOI:10.1016/j.neuroimage.2011.10.018)
(2012) NeuroImage, . Article in Press. 

a Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA
b Department of Radiology, Washington University School of Medicine, St. Louis, MO, USA
c Department of Pediatrics, Washington University School of Medicine, St. Louis, MO, USA
d Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, MO, USA
e Department of Psychology, Washington University in Saint Louis, St. Louis, MO, USA

Document Type: Article in Press
Source: Scopus


Acosta, M.T.a b , Bearden, C.E.c , Castellanos, X.F.d , Cutting, L.e , Elgersma, Y.f , Gioia, G.a , Gutmann, D.H.g , Lee, Y.-S.h , Legius, E.i , Muenke, M.b , North, K.i , Parada, L.F.j , Ratner, N.k , Hunter-Schaedle, K.l , Silva, A.J.c

The Learning Disabilities Network (LeaDNet): Using neurofibromatosis type 1 (NF1) as a paradigm for translational research
(2012) American Journal of Medical Genetics, Part A, . Article in Press. 


a The Gilbert Neurofibromatosis Institute, Children's National Medical Center, Washington District of Columbia
b National Human Genome Research Institute, National Institute of Health, Bethesda, Maryland
c University of California, Los Angeles, California
d New York University, New York, New York
e Vanderbilt University, Nashville, Tennessee
f Erasmus University, Rotterdam, The Netherlands
g Washington University School of Medicine, St. Louis, Missouri
h University of Leuven, Leuven, Belgium
i Children's Hospital at Westmead, University of Sydney, Sydney, Australia
j University of Texas Southwestern, Dallas, Texas
k Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
l Children's Tumor Foundation, New York, New York

Abstract
Learning disabilities and other cognitive disorders represent one of the most important unmet medical needs and a significant source of lifelong disability. To accelerate progress in this area, an international consortium of researchers and clinicians, the Learning Disabilities Network (LeaDNet), was established in 2006. Initially, LeaDNet focused on neurofibromatosis type 1 (NF1), a common single gene disorder with a frequency of 1:3,000. Although NF1 is best recognized as an inherited tumor predisposition syndrome, learning, cognitive, and neurobehavioral deficits account for significant morbidity in this condition and can have a profound impact on the quality of life of affected individuals. Recently, there have been groundbreaking advances in our understanding of the molecular, cellular, and neural systems underpinnings of NF1-associated learning deficits in animal models, which precipitated clinical trials using a molecularly targeted treatment for these deficits. However, much remains to be learned about the spectrum of cognitive, neurological, and psychiatric phenotypes associated with the NF1 clinical syndrome. In addition, there is a pressing need to accelerate the identification of specific clinical targets and treatments for these phenotypes. The successes with NF1 have allowed LeaDNet investigators to broaden their initial focus to other genetic disorders characterized by learning disabilities and cognitive deficits including other RASopathies (caused by changes in the Ras signaling pathway). The ultimate mission of LeaDNet is to leverage an international translational consortium of clinicians and neuroscientists to integrate bench-to-bedside knowledge across a broad range of cognitive genetic disorders, with the goal of accelerating the development of rational and biologically based treatments. © 2012 Wiley Periodicals, Inc.


Author Keywords
Learning disabilities;  Learning Disabilities Network;  Neurodevelopmental disorders;  Neurofibromatosis type 1;  RAS/MAPK pathway


Document Type: Article in Press
Source: Scopus

 

Stein, L.R., Imai, S.-i.
The dynamic regulation of NAD metabolism in mitochondria
(2012) Trends in Endocrinology and Metabolism, . Article in Press. 


Department of Developmental Biology, Washington University School of Medicine, St. Louis, MO 63110, USA

Abstract
Mitochondria are intracellular powerhouses that produce ATP and carry out diverse functions for cellular energy metabolism. Although the maintenance of an optimal NAD/NADH ratio is essential for mitochondrial function, it has recently become apparent that the maintenance of the mitochondrial NAD pool is also of crucial importance. The biosynthesis, transport, and catabolism of NAD and its key intermediates play an important role in the regulation of NAD-consuming mediators, such as sirtuins, poly-ADP-ribose polymerases, and CD38/157 ectoenzymes, in intra- and extracellular compartments. Mitochondrial NAD biosynthesis is also modulated in response to nutritional and environmental stimuli. In this article, we discuss this dynamic regulation of NAD metabolism in mitochondria to shed light on the intimate connection between NAD and mitochondrial function. © 2012 Elsevier Ltd. All rights reserved.


Document Type: Article in Press
Source: Scopus

 

Fox, I.K.a b , Brenner, M.J.c d , Johnson, P.J.a b , Hunter, D.A.a b , Mackinnon, S.E.a b
Axonal regeneration and motor neuron survival after microsurgical nerve reconstruction
(2012) Microsurgery, . Article in Press. 


a Division of Plastic and Reconstructive Surgery, Washington University School of Medicine, Saint Louis, MO
b Department of Surgery, Washington University School of Medicine, Saint Louis, MO
c Division of Otolaryngology-Head and Neck Surgery, Southern Illinois University School of Medicine, Springfield, IL
d Department of Surgery, Southern Illinois University School of Medicine, Springfield, IL

Abstract
Rodent models are used extensively for studying nerve regeneration, but little is known about how sprouting and pruning influence peripheral nerve fiber counts and motor neuron pools. The purpose of this study was to identify fluctuations in nerve regeneration and neuronal survival over time. One hundred and forty-four Lewis rats were randomized to end-to-end repair or nerve grafting (1.5 cm graft) after sciatic nerve transection. Quantitative histomorphometry and retrograde labeling of motor neurons were performed at 1, 3, 6, 9, 12, and 24 months and supplemented by electron microscopy. Fiber counts and motor neuron counts increased between 1 and 3 months, followed by plateau. End-to-end repair resulted in persistently higher fiber counts compared to the grafting for all time points (P < 0.05). Percent neural tissue and myelin width increased with time while fibrin debris dissipated. In conclusion, these data detail the natural history of regeneration and demonstrate that overall fiber counts may remain stable despite pruning. © 2012 Wiley Periodicals, Inc.


Document Type: Article in Press
Source: Scopus

 

Pearce, T.M., Moran, D.W.
Strategy-Dependent Encoding of Planned Arm Movements in the Dorsal Premotor Cortex
(2012) Science, pp. 1-6. Article in Press. 


Washington University in St. Louis, St. Louis, MO, USA

Abstract
The kinematic strategy encoded in motor cortical areas for classic straight-line reaching is remarkably simple and consistent across subjects, despite the complicated musculoskeletal dynamics that are involved. As tasks become more challenging, however, different conscious strategies may be utilized to improve perceived behavioral performance. We discovered that additional spatial information appeared both in single neurons and in the population code of monkey dorsal premotor cortex when obstacles impeded direct reach paths. The neural correlate of movement planning varied between subjects in a manner consistent with the use of different strategies to optimize task completion. These distinct planning strategies were manifested in the timing and strength of the information contained in the neural population code.


Document Type: Article in Press
Source: Scopus

 

Granados-Fuentes, D.a , Norris, A.J.b , Carrasquillo, Y.b , Nerbonne, J.M.b , Herzog, E.D.a
I A channels encoded by Kv1.4 and Kv4.2 regulate neuronal firing in the suprachiasmatic nucleus and circadian rhythms in locomotor activity
(2012) Journal of Neuroscience, 32 (29), pp. 10045-10052. 


a Department of Biology, Washington University, St. Louis, MO 63130-4899, United States
b Department of Molecular Biology and Pharmacology, School of Medicine, Washington University, St. Louis, MO 63130-4899, United States

Abstract
Neurons in the suprachiasmatic nucleus (SCN) display coordinated circadian changes in electrical activity that are critical for daily rhythms in physiology, metabolism, and behavior. SCN neurons depolarize spontaneously and fire repetitively during the day and hyperpolarize, drastically reducing firing rates, at night. To explore the hypothesis that rapidly activating and inactivating A-type (I A) voltage-gated K + (Kv) channels, which are also active at subthreshold membrane potentials, are critical regulators of the excitability of SCN neurons, we examined locomotor activity and SCN firing in mice lacking Kv1.4 (Kv1.4 -/-), Kv4.2 (Kv4.2 -/-), or Kv4.3 (Kv4.3 -/-), the pore-forming (α) subunits of I A channels. Mice lacking either Kv1.4 or Kv4.2 α subunits have markedly shorter (0.5 h) periods of locomotor activity than wild-type (WT) mice. In vitro extracellular multi-electrode recordings revealed that Kv1.4 -/-and Kv4.2 -/-SCN neurons display circadian rhythms in repetitive firing, but with shorter periods (0.5 h) than WT cells. In contrast, the periods of wheel-running activity in Kv4.3 -/- mice and firing in Kv4.3 -/- SCN neurons were indistinguishable from WT animals and neurons. Quantitative real-time PCR revealed that the transcripts encoding all three Kv channelα subunits, Kv1.4, Kv4.2, and Kv4.3, are expressed constitutively throughout the day and night in the SCN. Together, these results demonstrate that Kv1.4- and Kv4.2-encoded I A channels regulate the intrinsic excitability of SCN neurons during the day and night and determine the period and amplitude of circadian rhythms in SCN neuron firing and locomotor behavior. © 2012 the authors.


Document Type: Article
Source: Scopus

 

Rao, V.a b , DeAngelis, G.C.a c , Snyder, L.H.a
Neural correlates of prior expectations of motion in the lateral intraparietal and middle temporal areas
(2012) Journal of Neuroscience, 32 (29), pp. 10063-10074. 


a Department of Anatomy and Neurobiology, Washington University School of Medicine, Saint Louis, MO 63110, United States
b Department of Psychiatry, Massachusetts General Hospital, Boston, MA 02114, United States
c Department of Brain and Cognitive Sciences, University of Rochester, Rochester, NY 14627, United States

Abstract
Successful decision making involves combining observations of the external world with prior knowledge. Recent studies suggest that neural activity in macaque lateral intraparietal area (LIP) provides a useful window into this process. This study examines how rapidly changing prior knowledge about an upcoming sensory stimulus influences the computations that convert ensory signals into plans for action. Two monkeys performed a cued direction discrimination task, in which an arrow cue presented at the start of each trial communicated the prior probability of the direction of stimulus motion. We hypothesized that the cue would either shift the initial level of LIP activity before sensory evidence arrived, or it would scale sensory responses according to the prior probability of each stimulus, manifesting as a change in slope of LIP firing rates. Neural recordings demonstrated a clear shift in the activity level of LIP neurons following the arrow cue, which persisted into the presentation of the motion stimulus. No significant change in slope of responses was observed, suggesting that sensory gain was not strongly modulated. To confirm the latter observation, middle temporal area (MT) neurons were recorded during a version of the cued direction discrimination task, and we found no change in MT responses resulting from the presentation of the directional cue. These results suggest that information about an immediately upcoming stimulus does not scale the sensory response, but rather changes the amount of evidence that must be accumulated to reach a decision in areas that are involved in planning action. © 2012 the authors.


Document Type: Article
Source: Scopus

 

Rao, R.C.a , Dlouhy, B.J.b
Retinal detachment and fluoroquinolones [2]
(2012) JAMA - Journal of the American Medical Association, 308 (3), pp. 233-234. 


a Washington University School of Medicine, St Louis, MO, United States
b University of Iowa Hospitals and Clinics, Iowa City, United States

Document Type: Letter
Source: Scopus

 

Zhou, Y.a , Zeng, X.-H.a b , Lingle, C.J.a
Barium ions selectively activate BK channels via the Ca 2+-bowl site
(2012) Proceedings of the National Academy of Sciences of the United States of America, 109 (28), pp. 11413-11418. 


a Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO 63110, United States
b Division of Neuropathy and Psychosis, Institute of Life Science, Nanchang University, Nanchang, 33031, China

Abstract
Activation of Ca 2+-dependent BK channels is increased via binding of micromolar Ca 2+ to two distinct high-affinity sites per BK α-subunit. One site, termed the Ca 2+ bowl, is embedded within the second RCK domain (RCK2; regulator of conductance for potassium) of each α-subunit, while oxygen-containing residues in the first RCK domain (RCK1) have been linked to a separate Ca 2+ ligation site. Although both sites are activated by Ca 2+ and Sr 2+, Cd 2+ selectively favors activation via the RCK1 site. Divalent cations of larger ionic radius than Sr 2+ are thought to be ineffective at activating BK channels. Here we show that Ba 2+, better known as a blocker of K + channels, activates BK channels and that this effect arises exclusively from binding at the Ca 2+-bowl site. Compared with previous estimates for Ca 2+ bowl-mediated activation by Ca 2+, the affinity of Ba 2+ to the Ca 2+ bowl is reduced about fivefold, and coupling of binding to activation is reduced from
3.6 for Ca 2+ to about 2.8 for Ba 2+. These results support the idea that ionic radius is an important determinant of selectivity differences among different divalent cations observed for each Ca 2+-binding site.

Author Keywords
Allosteric regulation;  Barium;  Slo1 channels


Document Type: Article
Source: Scopus

 

Weidler, B.J.a , Multhaup, K.S.b , Faust, M.E.c
Accountability Reduces Unconscious Plagiarism
(2012) Applied Cognitive Psychology, 26 (4), pp. 626-634. 


a Washington University in St. Louis, St. Louis, MO, United States
b Washington University in St. Louis, St. Louis, MO, United States
c University of North Carolina at Charlotte, Charlotte, NC, United States

Abstract
Summary: We investigated how holding participants accountable for their responses affected unconscious plagiarism when solving a Boggle puzzle task (finding words in a 4×4 letter matrix). Both experimental and control participants (N=60) generated puzzle solutions with a computer partner, recalled their own previously generated solutions, and then produced new solutions to the puzzles. Accountability was manipulated by telling participants in the experimental group before beginning the initial-generation phase that at the end of the session, they would review their generated responses with the researcher (accountable participants). Accountable participants plagiarized less than control participants when generating words with the computer and generating new solutions on their own but not when they were attempting to recall words they initially generated. The data are discussed in terms of the leading theoretical explanation of unconscious plagiarism, the source-monitoring framework. © 2012 John Wiley & Sons, Ltd.


Document Type: Article
Source: Scopus

 

Jain, S.a , Ton, T.G.b , Perera, S.c , Zheng, Y.c , Stein, P.K.d , Thacker, E.e , Strotmeyer, E.S.f , Newman, A.B.f , Longstreth, W.T.b
Cardiovascular physiology in premotor Parkinson's disease: A neuroepidemiologic study
(2012) Movement Disorders, 27 (8), pp. 988-995. 


a University of Pittsburgh, School of Medicine, Department of Neurology, Pittsburgh, PA, United States
b University of Washington, School of Medicine, Department of Neurology, Seattle, WA, United States
c University of Pittsburgh, School of Medicine, Department of Medicine, Pittsburgh, PA, United States
d Washington University, School of Medicine, Heart Rate Variability Laboratory, St. Louis, MO, United States
e University of Washington, School of Public Health, Department of Epidemiology, Seattle, WA, United States
f University of Pittsburgh, Graduate School of Public Health, Department of Epidemiology, Pittsburgh, PA, United States

Abstract
Changes in cardiovascular physiology in Parkinson's disease (PD) are common and may occur prior to diagnostic parkinsonian motor signs. We investigated associations of electrocardiographic (ECG) abnormalities, orthostasis, heart rate variability, and carotid stenosis with the risk of PD diagnosis in the Cardiovascular Health Study, a community-based cohort of older adults. ECG abnormality, orthostasis (symptomatic or asymptomatic), heart rate variability (24-hour Holter monitoring), and any carotid stenosis (≥1%) by ultrasound were modeled as primary predictors of incident PD diagnosis using multivariable logistic regression. Incident PD cases were identified by at least 1 of the following: self-report, antiparkinsonian medication use, and ICD-9. If unadjusted models were significant, they were adjusted or stratified by age, sex, and smoking status, and those in which predictors were still significant (P ≤ .05) were also adjusted for race, diabetes, total cholesterol, low-density lipoprotein, blood pressure, body mass index, physical activity, education level, stroke, and C-reactive protein. Of 5888 participants, 154 incident PD cases were identified over 14 years of follow-up. After adjusting models with all covariates, those with any ECG abnormality (odds ratio [OR], 1.45; 95% CI, 1.02-2.07; P = .04) or any carotid stenosis (OR, 2.40; 95% CI, 1.40-4.09; P = .001) at baseline had a higher risk of incident PD diagnosis. Orthostasis and heart rate variability were not significant predictors. This exploratory study suggests that carotid stenosis and ECG abnormalities occur prior to motor signs in PD, thus serving as potential premotor features or risk factors for PD diagnosis. Replication is needed in a population with more thorough ascertainment of PD onset. © 2012 Movement Disorder Society.


Author Keywords
Cardiovascular physiology;  Neurodegeneration;  Neuroepidemiology;  Nonmotor features;  Parkinson's disease


Document Type: Article
Source: Scopus

 

Chen, L.-S.a b c d e f g h , Baker, T.B.a b c d e f g h , Piper, M.E.a b c d e f g h , Breslau, N.a b c d e f g h , Cannon, D.S.a b c d e f g h , Doheny, K.F.a b c d e f g h , Gogarten, S.M.a b c d e f g h , Johnson, E.O.a b c d e f g h , Saccone, N.L.a b c d e f g h , Wang, J.C.a b c d e f g h , Weiss, R.B.a b c d e f g h , Goate, A.M.a b c d e f g h , Bierut, L.J.a b c d e f g h
Interplay of genetic risk factors (CHRNA 5-CHRNA 3-CHRNB4) and cessation treatments in smoking cessation success
(2012) American Journal of Psychiatry, 169 (7), pp. 735-742. 

a Department of Psychiatry, Department of Genetics, Washington University School of Medicine, St. Louis, United States
b Center for Tobacco Research and Intervention, School of Medicine and Public Health, University of Wisconsin, Madison, WI, United States
c Department of Epidemiology, Michigan State University, East Lansing, MI, United States
d Department of Human Genetics, Eccles Institute of Human Genetics, Salt Lake City, UT, United States
e Department of Psychiatry, University of Utah School of Medicine, Salt Lake City, UT, United States
f Institute of Genetic Medicine, Johns Hopkins University, Baltimore, MD, United States
g Department of Biostatistics, University of Washington, Seattle, WA, United States
h Division of Health, Social, and Economic Research, Research Triangle Institute, Research Triangle Park, NC, United States

Abstract
Objective: Smoking is highly intractable, and the genetic influences on cessation are unclear. Identifying the genetic factors affecting smoking cessation could elucidate the nature of tobacco dependence, enhance risk assessment, and support development of treatment algorithms. This study tested whether variants in the nicotinic receptor gene cluster CHRNA5-CHRNA3-CHRNB4 predict age at smoking cessation and relapse after an attempt to quit smoking. Method: In a community-based, crosssectional study (N=5,216) and a randomized comparative effectiveness smoking cessation trial (N=1,073), the authors used Cox proportional hazard models and logistic regression to model the relationships of smoking cessation (self-reported quit age in the community study and point-prevalence abstinence at the end of treatment in the clinical trial) to three common haplotypes in the CHRNA5-CHRNA3-CHRNB4 region defined by rs16969968 and rs680244. Results: The genetic variants in the CHRNA5-CHRNA3-CHRNB4 region that predict nicotine dependence also predicted a later age at smoking cessation in the community sample. In the smoking cessation trial, haplotype predicted abstinence at end of treatment in individuals receiving placebo but not among individuals receiving active medication. Haplotype interacted with treatment in affecting cessation success. Conclusions: Smokers with the high-risk haplotype were three times as likely to respond to pharmacologic cessation treatments as were smokers with the low-risk haplotype. The high-risk haplotype increased the risk of cessation failure, and this increased risk was ameliorated by cessation pharmacotherapy. By identifying a high-risk genetic group with heightened response to smoking cessation pharmacotherapy, this work may support the development of personalized cessation treatments.


Document Type: Article
Source: Scopus

 

Dasgupta, B.a , Ju, J.S.b , Sasaki, Y.e , Liu, X.a , Jung, S.-R.c , Higashida, K.c , Lindquist, D.d , Milbrandt, J.e
The AMPK ß2 Subunit Is Required for Energy Homeostasis during Metabolic Stress
(2012) Molecular and Cellular Biology, 32 (14), pp. 2837-2848. 


a Department of Pediatrics, Division of Hematology and Oncology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States
b Department of Neurology, Washington University School of Medicine, St. Louis, MO, United States
c Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO, United States
d Imaging Research Center, Department of Radiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States
e Department of Genetics, HOPE Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO, United States

Abstract
AMP activated protein kinase (AMPK) plays a key role in the regulatory network responsible for maintaining systemic energy homeostasis during exercise or nutrient deprivation. To understand the function of the regulatory ß2 subunit of AMPK in systemic energy metabolism, we characterized ß2 subunit-deficient mice. Using these mutant mice, we demonstrated that the ß2 subunit plays an important role in regulating glucose, glycogen, and lipid metabolism during metabolic stress. The ß2 mutant animals failed to maintain euglycemia and muscle ATP levels during fasting. In addition, ß2-deficient animals showed classic symptoms of metabolic syndrome, including hyperglycemia, glucose intolerance, and insulin resistance when maintained on a high-fat diet (HFD), and were unable to maintain muscle ATP levels during exercise. Cell surface-associated glucose transporter levels were reduced in skeletal muscle from ß2 mutant animals on an HFD. In addition, they displayed poor exercise performance and impaired muscle glycogen metabolism. These mutant mice had decreased activation of AMPK and deficits in PGC1ß-mediated transcription in skeletal muscle. Our results highlight specific roles of AMPK complexes containing the ß2 subunit and suggest the potential utility of AMPK isoform-specific pharmacological modulators for treatment of metabolic, cardiac, and neurological disorders. © 2012, American Society for Microbiology.


Document Type: Article
Source: Scopus

 

Schwartz, Y.a , Barbot, A.a , Thyreau, B.a , Frouin, V.a , Varoquaux, G.a b , Siram, A.c , Marcus, D.S.c , Poline, J.-B.a d
PyXNAT: XNAT in Python
(2012) Frontiers in Neuroinformatics, (MAY), . 


a CEA, DSV, I2BM, Neurospin Bât 145, Gif-sur-Yvette, France
b Parietal Team, INRIA Saclay Ile-de-France, Saclay, France
c Department of Radiology, Washington University School of Medicine, St. Louis, MO, United States
d Henry H. Wheeler Jr. Brain Imaging Center, University of California at Berkeley, Berkeley, CA, United States

Abstract
As neuroimaging databases grow in size and complexity, the time researchers spend investigating and managing the data increases to the expense of data analysis. As a result, investigators rely more and more heavily on scripting using high-level languages to automate data management and processing tasks. For this, a structured and programmatic access to the data store is necessary. Web services are a first step toward this goal. They however lack in functionality and ease of use because they provide only low-level interfaces to databases. We introduce here PyXNAT, a Python module that interacts with The Extensible Neuroimaging Archive Toolkit (XNAT) through native Python calls across multiple operating systems. The choice of Python enables PyXNAT to expose the XNAT Web Services and unify their features with a higher level and more expressive language. PyXNAT provides XNAT users direct access to all the scientific packages in Python. Finally PyXNAT aims to be efficient and easy to use, both as a back-end library to build XNAT clients and as an alternative front-end from the command line. © 2012 Schwartz, Barbot, Thyreau, Frouin, Varoquaux, Siram, Marcus and Poline.


Author Keywords
Database;  Neuroimaging;  Neuroinformatics;  Python;  XNAT


Document Type: Article
Source: Scopus

 

Repovš, G.a , Barch, D.M.b
Working memory related brain network connectivity in individuals with schizophrenia and their siblings
(2012) Frontiers in Human Neuroscience, (MAY 2012), art. no. 137, pp. 1-15. 


a Department of Psychology, University of Ljubljana, Askerceva 2, SI-1000 Ljubljana, Slovenia
b Department of Psychology, Washington University in St Louis, St. Louis, United States

Abstract
A growing number of studies have reported altered functional connectivity in schizophrenia during putatively "task-free" states and during the performance of cognitive tasks. However, there have been few systematic examinations of functional connectivity in schizophrenia across rest and different task states to assess the degree to which altered functional connectivity reflects a stable characteristic or whether connectivity changes vary as a function of task demands. We assessed functional connectivity during rest and during three working memory loads of an N-back task (0-back, 1-back, 2-back) among: (1) individuals with schizophrenia (N = 19); (2) the siblings of individuals with schizophrenia (N = 28); (3) healthy controls (N = 10); and (4) the siblings of healthy controls (N = 17). We examined connectivity within and between four brain networks: (1) frontal-parietal (FP); (2) cingulo-opercular (CO); (3) cerebellar (CER); and (4) default mode (DMN). In terms of within-network connectivity, we found that connectivity within the DMN and FP increased significantly between resting state and 0-back, while connectivity within the CO and CER decreased significantly between resting state and 0-back. Additionally, we found that connectivity within both the DMN and FP was further modulated by memory load. In terms of between network connectivity, we found that the DMN became significantly more "anti-correlated" with the FP, CO, and CER networks during 0-back as compared to rest, and that connectivity between the FP and both CO and CER networks increased with memory load. Individuals with schizophrenia and their siblings showed consistent reductions in connectivity between both the FP and CO networks with the CER network, a finding that was similar in magnitude across rest and all levels of working memory load. These findings are consistent with the hypothesis that altered functional connectivity in schizophrenia reflects a stable characteristic that is present across cognitive states. © 2012 Repovš and Barch.


Author Keywords
Cerebellum;  Cognitive control;  Functional connectivity;  Risk;  Schizophrenia;  Task;  Working memory


Document Type: Article
Source: Scopus

 

Meiran, N.a , Cole, M.W.b , Braver, T.S.b
When planning results in loss of control: Intention-based reflexivity and working-memory
(2012) Frontiers in Human Neuroscience, (MAY 2012), . 


a Department of Psychology and Zlotowski Center for Neuroscience, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel
b Department of Psychology, Washington University, St. Louis, MO, United States

Abstract
In this review, the authors discuss the seemingly paradoxical loss of control associated with states of high readiness to execute a plan, termed "intention-based reflexivity." The review suggests that the neuro-cognitive systems involved in the preparation of novel plans are different than those involved in preparation of practiced plans (i.e., those that have been executed beforehand). When the plans are practiced, intention-based reflexivity depends on the prior availability of response codes in long-term memory (LTM). When the plans are novel, reflexivity is observed when the plan is pending and the goal has not yet been achieved. Intention-based reflexivity also depends on the availability of working-memory (WM) limited resources and the motivation to prepare. Reflexivity is probably related to the fact that, unlike reactive control (once a plan is prepared), proactive control tends to be relatively rigid. © 2012 Meiran, Cole and Braver.


Author Keywords
Intention;  Prefrontal cortex;  Preparation;  Proactive control;  Reflexivity;  Working-memory


Document Type: Article
Source: Scopus

 

Aldrich, M.B.a , Marshall, M.V.a , Sevick-Muraca, E.M.a , Lanza, G.b , Kotyk, J.b , Culver, J.b , Wang, L.V.b , Uddin, J.c , Crews, B.C.c , Marnett, L.J.c , Liao, J.C.d , Contag, C.d , Crawford, J.M.e , Wang, K.f , Reisdorph, B.g , Appelman, H.h , Kim Turgeon, D.i , eyer, C.j , Wang, T.k
Seeing it through: Translational validation of new medical imaging modalities
(2012) Biomedical Optics Express, 3 (4), pp. 764-776. 


a Center for Molecular Imaging, The Brown Foundation Institute for Molecular Medicine, The University of Texas Health Science Center-Houston, 1825 Pressler, 330-07, Houston, TX 77030, United States
b Department of Biomedical Engineering, Washington University in St. Louis, Campus Box 1097, One Brookings Drive, St. Louis, MO 63130, United States
c Department of Biochemistry, Vanderbilt University Medical Center, 850 Robinson Research Building, Nashville, TN 37232, United States
d Department of Pediatrics, Stanford University School of Medicine, Clark Center, East Wing E150, 318 Campus Drive, Stanford, CA 94305, United States
e Department of Pathology, Hofstra North Shore-LIJ College of Medicine, 10 Nevada Drive, Lake Success, NY 11042, United States
f Gastroenterology and Hepatology, Mayo Clinic Rochester, 200 First Street SW, Rochester, MN 55905, United States
g Michigan Institute for Clinical and Health Research, University of Michigan Medical School, 2800 Plymouth Road, NCRC Building 400, #4023, Ann Arbor, MI 48109, United States
h Department of Pathology, University of Michigan Medical School, 1301 Catherine, Ann Arbor, MI 48109, United States
i Department of Internal Medicine, University of Michigan Medical School, 1500 East Medical Center Drive, Ann Arbor, MI 48109, United States
j Department of Radiology, University of Michigan Medical School, 109 Zina Pitcher Place, Ann Arbor, MI 48109, United States
k Departments of Medicine and Biomedical Engineering, University of Michigan Medical School, 109 Zina Pitcher Place, Ann, United States

Abstract
Medical imaging is an invaluable tool for diagnosis, surgical guidance, and assessment of treatment efficacy. The Network for Translational Research (NTR) for Optical Imaging consists of four research groups working to "bridge the gap" between lab discovery and clinical use of fluorescence- and photoacoustic-based imaging devices used with imaging biomarkers. While the groups are using different modalities, all the groups face similar challenges when attempting to validate these systems for FDA approval and, ultimately, clinical use. Validation steps taken, as well as future needs, are described here. The group hopes to provide translational validation guidance for itself, as well as other researchers. © 2012 Optical Society of America.


Document Type: Article
Source: Scopus

 

Macones, G.A., Odibo, A., Stamilio, D.M., Cahill, A.G.
Discussion: 'Sleep apnea and adverse pregnancy outcomes' by Chen et al.
(2012) American journal of obstetrics and gynecology, 206 (2), pp. e1-2. 


Mitchell and Elaine Yanow Professor and Head, Department of Obstetrics and Gynecology, Washington University in St. Louis, St Louis, MO, USA.

Document Type: Note
Source: Scopus

 

Lester, R.J.
How Do I Code for Black Fingernail Polish? Finding the Missing Adolescent in Managed Mental Health Care
(2011) Ethos, 39 (4), pp. 481-496. 


Washington University in St. Louis, United States

Abstract
In this article, I examine clinical dilemmas in treating adolescents with eating disorders under the U.S. managed healthcare system. Managed care is built on a rational choice model of human behavior with little room for considering developmental processes. In this model, adolescents figure as little more than failed adults. This poses significant problems: if treatment providers prioritize developmental issues over quantifiable behavioral milestones, they risk jeopardizing continued coverage for their clients. If they prioritize quantifiable behavioral change without attending to underlying developmental concerns, they risk not affecting lasting change. Through a case study of a client in treatment for an eating disorder, I illustrate how this dilemma frames everyday encounters and negatively impacts client care, while at the same time missing developmentally meaningful opportunities for healing. An outline for a proposed applied psychiatric anthropology is presented, together with specific recommendations for adolescent mental health policy, research, and practice. © 2011 by the American Anthropological Association.


Author Keywords
Adolescence;  Applied psychiatric anthropology;  Eating disorders;  Managed care;  Mental health


Document Type: Article
Source: Scopus

 

Rao, R.C.a , Hennig, A.K.a , Malik, M.T.A.c , Chen, D.F.c d , Chen, S.a b
Epigenetic regulation of retinal development and disease
(2011) Journal of Ocular Biology, Diseases, and Informatics, 4 (3), pp. 121-136. 


a Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, 660 South Euclid Ave, St. Louis, MO 63110, United States
b Department of Developmental Biology, Washington University School of Medicine, 660 South Euclid Ave, St. Louis, MO 63110, United States
c Schepens Eye Research Institute, Massachusetts Eye and Ear, Department of Ophthalmology, Boston, MA, United States
d VA Boston Healthcare System, 150 South Huntington Ave, Boston, MA, United States

Abstract
Epigenetic regulation, includingDNAmethylation, histone modifications, and chromosomal organization, is emerging as a new layer of transcriptional regulation in retinal development and maintenance. Guided by intrinsic transcription factors and extrinsic signaling molecules, epigenetic regulation can activate and/or repress the expression of specific sets of genes, therefore playing an important role in retinal cell fate specification and terminal differentiation during development as well as maintaining cell function and survival in adults. Here, we review the major findings that have linked these mechanisms to the development and maintenance of retinal structure and function, with a focus on ganglion cells and photoreceptors. The mechanisms of epigenetic regulation are highly complex and vary among different cell types. Understanding the basic principles of these mechanisms and their regulatory pathways may provide new insight into the pathogenesis of retinal diseases associated with transcription dysregulation, and new therapeutic strategies for treatment. © Springer Science+Business Media, LLC 2011.


Author Keywords
Cell type-specific transcription;  Chromatin modifications;  Neuronal development and disease


Document Type: Review
Source: Scopus