Arts & Sciences Brown School McKelvey School Medicine Weekly Publications

WashU weekly Neuroscience publications

"The Open Source GAITOR Suite for Rodent Gait Analysis" (2018) Scientific Reports

The Open Source GAITOR Suite for Rodent Gait Analysis
(2018) Scientific Reports, 8 (1), art. no. 9797, . 

Jacobs, B.Y.a , Lakes, E.H.a , Reiter, A.J.b , Lake, S.P.b , Ham, T.R.c , Leipzig, N.D.c , Porvasnik, S.L.a , Schmidt, C.E.a , Wachs, R.A.a d , Allen, K.D.a

a University of Florida, J. Crayton Pruitt Family Department of Biomedical Engineering, Gainesville, United States
b Washington University in St. Louis, School of Engineering and Applied Science, St. Louis, United States
c University of Akron, Chemical and Biomolecular Engineering, Akron, United States
d University of Nebraska-Lincoln, Biological Systems Engineering, Lincoln, United States

Abstract
Locomotive changes are often associated with disease or injury, and these changes can be quantified through gait analysis. Gait analysis has been applied to preclinical studies, providing quantitative behavioural assessment with a reasonable clinical analogue. However, available gait analysis technology for small animals is somewhat limited. Furthermore, technological and analytical challenges can limit the effectiveness of preclinical gait analysis. The Gait Analysis Instrumentation and Technology Optimized for Rodents (GAITOR) Suite is designed to increase the accessibility of preclinical gait analysis to researchers, facilitating hardware and software customization for broad applications. Here, the GAITOR Suite’s utility is demonstrated in 4 models: a monoiodoacetate (MIA) injection model of joint pain, a sciatic nerve injury model, an elbow joint contracture model, and a spinal cord injury model. The GAITOR Suite identified unique compensatory gait patterns in each model, demonstrating the software’s utility for detecting gait changes in rodent models of highly disparate injuries and diseases. Robust gait analysis may improve preclinical model selection, disease sequelae assessment, and evaluation of potential therapeutics. Our group has provided the GAITOR Suite as an open resource to the research community at www.GAITOR.org, aiming to promote and improve the implementation of gait analysis in preclinical rodent models. © 2018 The Author(s).

Document Type: Article
Source: Scopus
Access Type: Open Access

"Affective instability predicts the course of depression in late middle-age and older adulthood" (2018) Journal of Affective Disorders

Affective instability predicts the course of depression in late middle-age and older adulthood
(2018) Journal of Affective Disorders, 239, pp. 72-78. 

Eldesouky, L., Thompson, R.J., Oltmanns, T.F., English, T.

Department of Psychological & Brain Sciences, Washington University in St. Louis, One Brookings Drive, St. Louis, United States

Abstract
Background: Affective instability is a facet of emotion dysregulation that characterizes various mental disorders, including Major Depressive Disorder (MDD). However, it is unclear as to how affective instability predicts the course of MDD. It is also unknown whether affective instability is a relevant predictor of MDD in later adulthood, a period when there is a decrease in both affective instability and MDD prevalence. Thus, we investigated the role of affective instability in the course of MDD in a sample of late middle-age and older adults. Methods: Using a longitudinal design over five years, 1,630 adults aged 55–64 years (M = 59.60, SD = 2.70) completed a baseline assessment of affective instability (self-report, informant-report, interviewer-report), three assessments of MDD (computerized interview), and eight assessments of depressive symptoms (self-report). Results: Baseline affective instability positively predicted the likelihood of having lifetime major depressive episodes (MDE) and first-time MDEs, as well as depressive symptoms up to five years later. However, affective instability did not predict remission or having more depressive symptoms over time. These findings held when controlling for neuroticism. Limitations: We only assessed affective instability at the baseline, did not investigate specific mechanisms or recurrence, and focused on middle-age and older adults. Conclusions: Our findings replicate and extend prior work by showing that affective instability is differentially related to multiple aspects of MDD’s course and remains an important predictor of MDD even in older age. We discuss implications for the role of affective instability in MDD across the lifespan. © 2018 Elsevier B.V.

Author Keywords
Affective instability;  Depression course;  Emotion dysregulation;  Older adulthood;  Risk factors

Document Type: Article
Source: Scopus

"Utility of CT angiography in screening for traumatic cerebrovascular injury" (2018) Clinical Neurology and Neurosurgery

Utility of CT angiography in screening for traumatic cerebrovascular injury
(2018) Clinical Neurology and Neurosurgery, 172, pp. 27-30. 

Orlowski, H.L.P., Kansagra, A.P., Sipe, A.L., Miller-Thomas, M.M., Vo, K.D., Goyal, M.S.

Mallinckrodt Institute of Radiology, Washington University School of Medicine, MO510 S. Kingshighway Boulevard, St. Louis, MO, United States

Abstract
Objective: Computed tomographic angiography (CTA) is increasingly utilized to evaluate for traumatic cerebrovascular injury (TCVI). The purpose of this study was to determine the yield, management effect, and risk of stroke or poor outcome of a positive CTA in a large cohort of trauma patients. Patients and Methods: A retrospective analysis was performed on 1290 consecutive trauma patients that underwent head and/or neck CTA at our level I trauma center from 2006 to 2015. Clinical variables assessed include mechanism of injury, neurological status, CTA findings, subsequent imaging results, patient management, and clinical outcomes. Results: Among 1290 patients who underwent CTA, 200 (15.5%) were positive for TCVI, higher in blunt than penetrating trauma patients. In a generalized linear model, factors that increased likelihood of positive CTA included multiple cervical fractures, fractures with foraminal involvement, gunshot injury, Glasgow Coma Scale ≤ 13, and focal neurological deficit. Excluding cases with these factors lowered the positive rate to 4.3%. Of the 200 CTA-positives, 99 were treated for TCVI and 9 (4.5%) developed a subsequent stroke as compared to 5 (0.5%) in CTA-negative patients (odds ratio 10.2, Fisher exact test, p < 0.001). Risk of death or nursing facility discharge location was also higher in CTA-positive patients, correcting for age and presenting GCS (p < 0.01). Conclusion: CTA had a modest yield in identifying TCVI in this cohort. When positive, CTA influenced management and predicted an increased risk of subsequent stroke and poor outcome. © 2018

Author Keywords
Computed tomographic angiography;  Imaging;  Screening;  Stroke;  Trauma;  Vascular injury

Document Type: Article
Source: Scopus

"Parallel Processing of Negative Feedback: E Unum Pluribus" (2018) Neuron

Parallel Processing of Negative Feedback: E Unum Pluribus
(2018) Neuron, 99 (1), pp. 5-7. 

Hsiang, J.-C.a b , Kerschensteiner, D.a c d e

a Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, Saint Louis, MO, United States
b Graduate Program in Neuroscience, Washington University School of Medicine, Saint Louis, MO, United States
c Department of Neuroscience, Washington University School of Medicine, Saint Louis, MO, United States
d Department of Biomedical Engineering, Washington University School of Medicine, Saint Louis, MO, United States
e Hope Center for Neurological Disorders, Washington University School of Medicine, Saint Louis, MO, United States

Abstract
How do canonical computational elements interact to shape neural circuit function? In this issue of Neuron, Drinnenberg et al. (2018) show that parallel processing converts unitary negative feedback at the first synapse of the retina into diverse output signals to the brain.

How do canonical computational elements interact to shape neural circuit function? In this issue of Neuron, Drinnenberg et al. (2018) show that parallel processing converts unitary negative feedback at the first synapse of the retina into diverse output signals to the brain. © 2018 Elsevier Inc.

Document Type: Short Survey
Source: Scopus

"Triggering receptor expressed on myeloid cells 2 (TREM2): a potential therapeutic target for Alzheimer disease?" (2018) Expert Opinion on Therapeutic Targets

Triggering receptor expressed on myeloid cells 2 (TREM2): a potential therapeutic target for Alzheimer disease?
(2018) Expert Opinion on Therapeutic Targets, 22 (7), pp. 587-598.

Deming, Y.a , Li, Z.a , Benitez, B.A.b , Cruchaga, C.a c d e  

a Department of Psychiatry, 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 Developmental Biology, Washington University School of Medicine, St Louis, MO, United States
d Knight Alzheimer’s Disease Research Center, Washington University School of Medicine, St Louis, MO, United States
e Hope Center for Neurological Disorders, Washington University School of Medicine, St Louis, MO, United States

Abstract
Introduction: There are currently no effective therapeutics for Alzheimer disease (AD). Clinical trials targeting amyloid beta thus far have shown very little benefit and only in the earliest stages of disease. These limitations have driven research to identify alternative therapeutic targets, one of the most promising is the triggering receptor expressed on myeloid cells 2 (TREM2). Areas covered: Here, we review the literature to-date and discuss the potentials and pitfalls for targeting TREM2 as a potential therapeutic for AD. We focus on research in animal and cell models for AD and central nervous system injury models which may help in understanding the role of TREM2 in disease. Expert opinion: Studies suggest TREM2 plays a key role in AD pathology; however, results have been conflicting about whether TREM2 is beneficial or harmful. More research is necessary before designing TREM2-targeting therapies. Successful therapeutics will most likely be administered early in disease. © 2018, © 2018 Informa UK Limited, trading as Taylor & Francis Group.

Author Keywords
Alzheimer disease;  cerebrospinal fluid;  genetic association;  microglia;  TREM2

Document Type: Review
Source: Scopus

"The impact of traditional neuroimaging methods on the spatial localization of cortical areas" (2018) Proceedings of the National Academy of Sciences of the United States of America

The impact of traditional neuroimaging methods on the spatial localization of cortical areas
(2018) Proceedings of the National Academy of Sciences of the United States of America, 115 (27), pp. E6356-E6365. 

Coalson, T.S.a , Van Essen, D.C.a , Glasser, M.F.a b

a Department of Neuroscience, Washington University School of Medicine, St. Louis, MO, United States
b St. Luke’s Hospital, St. Louis, MO, United States

Abstract
Localizing human brain functions is a long-standing goal in systems neuroscience. Toward this goal, neuroimaging studies have traditionally used volume-based smoothing, registered data to volume-based standard spaces, and reported results relative to volume-based parcellations. A novel 360-area surface-based cortical parcellation was recently generated using multimodal data from the Human Connectome Project, and a volume-based version of this parcellation has frequently been requested for use with traditional volume-based analyses. However, given the major methodological differences between traditional volumetric and Human Connectome Project-style processing, the utility and interpretability of such an altered parcellation must first be established. By starting from automatically generated individual-subject parcellations and processing them with different methodological approaches, we show that traditional processing steps, especially volume-based smoothing and registration, substantially degrade cortical area localization compared with surface-based approaches. We also show that surface-based registration using features closely tied to cortical areas, rather than to folding patterns alone, improves the alignment of areas, and that the benefits of high-resolution acquisitions are largely unexploited by traditional volume-based methods. Quantitatively, we show that the most common version of the traditional approach has spatial localization that is only 35% as good as the best surface-based method as assessed using two objective measures (peak areal probabilities and “captured area fraction” for maximum probability maps). Finally, we demonstrate that substantial challenges exist when attempting to accurately represent volume-based group analysis results on the surface, which has important implications for the interpretability of studies, both past and future, that use these volume-based methods. © 2018 National Academy of Sciences. All Rights Reserved.

Author Keywords
Blurring;  CIFTI grayordinates;  Cross-subject alignment;  Neuroimaging analysis;  Standard space

Document Type: Article
Source: Scopus

"Fingolimod's Impact on MRI Brain Volume Measures in Multiple Sclerosis: Results from MS-MRIUS" (2018) Journal of Neuroimaging

Fingolimod’s Impact on MRI Brain Volume Measures in Multiple Sclerosis: Results from MS-MRIUS
(2018) Journal of Neuroimaging, 28 (4), pp. 399-405. 

Zivadinov, R.a b , Medin, J.c , Khan, N.d , Korn, J.R.e , Bergsland, N.a , Dwyer, M.G.a , Chitnis, T.f , Naismith, R.T.g , Alvarez, E.h , Kinkel, P.i , Cohan, S.j , Hunter, S.F.k , Silva, D.c , Weinstock-Guttman, B.l , on behalf of MS-MRIUS investigatorsm

a Buffalo Neuroimaging Analysis Center, Buffalo, Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, The State University of New York, Buffalo, NY, United States
b Center for Biomedical Imaging, Clinical Translational Science Institute, University at Buffalo, The State University of New York, Buffalo, NY, United States
c Novartis Pharma AG, Basel, Switzerland
d RWECNJ, United States
e QuintilesIMS, Burlington, VT, United States
f Partners MS Center, Brigham and Women’s Hospital, Boston, MA, United States
g Washington University, St. Louis, MO, United States
h Department of Neurology, University of Colorado School of MedicineCO, United States
i Kinkel Neurological Center, Williamsville, NY, United States
j Providence St. Vincent Medical Center, Portland, OR, United States
k Advanced Neurosciences Institute, Franklin, TN, United States
l Jacobs Multiple Sclerosis Center, Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, The State University of New York, Buffalo, NY, United States

Abstract
BACKGROUND AND PURPOSE: Evidence is needed to understand the effect of fingolimod on slowing down brain atrophy progression in multiple sclerosis (MS) patients in clinical practice. We investigated the effect of fingolimod on brain atrophy in MS patients with active disease (clinically and/or magnetic resonance imaging [MRI]) versus no evidence of active disease (NEAD). METHODS: MS and clinical outcome and MRI in the United States (MS-MRIUS) is a multicenter, retrospective study that included 590 relapsing-remitting MS patients, who initiated fingolimod, and were followed for a median of 16 months. Patients with active disease at baseline (245, 41.5%) were defined as those who had one or more relapses in the year previous starting fingolimod, and/or displayed gadolinium enhancing lesions(s) at baseline MRI scan, whereas patients with NEAD at baseline (345, 58.5%) did not fulfill these criteria. Annualized percentage brain volume change (PBVC) and percentage lateral ventricle volume change (PLVVC) over the follow-up were analyzed in both groups. RESULTS: Over the follow-up, the rate of PBVC was −.38% in active disease and −.25% in NEAD patients (P =.076), whereas PLLVC was 1.76% in active disease and.28% in NEAD patients (P =.046). No changes in timed 25-foot walk (P =.619) and Expanded Disability Status Scale (P =.275) scores or MRI lesion accumulation (P > 0.08) were detected, although the active disease group had a higher proportion of relapses during the follow-up period (P =.02). CONCLUSIONS: The study provides real-world evidence that rate of brain atrophy in MS patients with underlying active disease and NEAD in fingolimod treated patients is below the established pathological cutoff for loss of whole brain volume (>−.4%) or expansion of lateral ventricles (> 3.5%). Copyright © 2018 by the American Society of Neuroimaging

Author Keywords
active disease;  brain atrophy;  clinical routine;  Multiple sclerosis;  no evidence of active disease (NEAD)

Document Type: Article
Source: Scopus

"Executive performance on the preschool executive task assessment in children with sickle cell anemia and matched controls" (2018) Child Neuropsychology

Executive performance on the preschool executive task assessment in children with sickle cell anemia and matched controls
(2018) Child Neuropsychology, pp. 1-8. Article in Press. 

Downes, M.a b , Kirkham, F.J.b , Berg, C.c , Telfer, P.d , de Haan, M.b

a School of Psychology, University College Dublin, Dublin, Ireland
b Developmental Neurosciences, UCL Great Ormond Street Institute of Child Health, London, UK
c School of Medicine, Washington University in St. Louis, MO, USA
d Barts Health NHS Trust, Royal London Hospital, London, UK

Abstract
Executive deficits are commonly reported in children with sickle cell anemia. Earlier identification of executive deficits would give more scope for intervention, but this cognitive domain has not been routinely investigated due to a lack of age-appropriate tasks normed for preschool children. In particular, information relating to patient performance on an executive task that reflects an everyday activity in the classroom could provide important insight and practical recommendations for the classroom teacher at this key developmental juncture as they enter the academic domain. The performance of 22 children with sickle cell anemia was compared to 24 matched control children on the Preschool Executive Task Assessment. Findings reveal that children with sickle cell anemia are performing poorer than their matched peers on this multi-step assessment. In particular, children with sickle cell anemia required more structured support to shift focus after a completed step, as reflected by poorer scores in the quantitative Sequencing and Completion domains. They also required more support to stay on task, as seen by poorer ratings in the qualitative Distractibility domain. Abbreviations:PETA: Preschool Executive Task Assessment; SCA: Sickle Cell Anemia; EF: Executive Functioning. © 2018 Informa UK Limited, trading as Taylor & Francis Group

Author Keywords
Executive function;  neurodevelopmental disorders;  neuropsychological assessment;  preschool;  sickle cell anemia;  sickle cell disease

Document Type: Article in Press
Source: Scopus

"Focal traumatic rupture of a dermoid cyst in a pediatric patient: case report and literature review" (2018) Child's Nervous System

Focal traumatic rupture of a dermoid cyst in a pediatric patient: case report and literature review
(2018) Child’s Nervous System, pp. 1-6. Article in Press. 

Akbari, S.H.A.a b , Somasundaram, A.a b , Ferguson, C.J.c , Roland, J.L.a b , Smyth, M.D.a b , Strahle, J.M.a b

a Department of Neurological Surgery, St. Louis Children’s Hospital, Washington University in St. Louis School of Medicine, 1 Children’s Place, St. Louis, MO, United States
b Department of Neurological Surgery, Washington University in St. Louis School of Medicine, 660 South Euclid Ave, St. Louis, MO, United States
c Department of Pathology and Immunology, Washington University in St. Louis School of Medicine, 660 South Euclid Ave, St. Louis, MO, United States

Abstract
Background: Dermoid cysts are rare congenital teratomas that can occasionally rupture and cause chemical meningitis, neurological deficit, or hydrocephalus. Rarely, dermoid cysts in the pediatric population can rupture spontaneously and even more rarely rupture due to trauma. To date, there are only five documented cases of traumatic rupture of a dermoid cyst. Case summary: A 2-year-old male presented with 5 days of left eye ptosis and ophthalmoplegia after suffering a fall and was found to have a ruptured left anterior clinoid dermoid cyst that was surgically resected. The patient had significant improvement postoperatively. Significance: To the authors’ knowledge, this is the first reported case in the literature of a ruptured dermoid cyst after trauma in a pediatric patient and the first case of a traumatically ruptured dermoid cyst presenting with neurological deficit. © 2018 Springer-Verlag GmbH Germany, part of Springer Nature

Author Keywords
Anterior clinoid;  Dermoid cyst;  Dermoid cyst rupture;  Giant cell reaction;  Ophthalmoplegia

Document Type: Article in Press
Source: Scopus

"Item-specific processing reduces false recognition in older and younger adults: Separating encoding and retrieval using signal detection and the diffusion model" (2018) Memory and Cognition

Item-specific processing reduces false recognition in older and younger adults: Separating encoding and retrieval using signal detection and the diffusion model
(2018) Memory and Cognition, pp. 1-15. Article in Press. 

Huff, M.J.a , Aschenbrenner, A.J.b

a Department of Psychology, The University of Southern Mississippi, Hattiesburg, MS, United States
b Department of Neurology, Washington University in St. Louis, St. Louis, MO, United States

Abstract
Our study examined processing effects in improving memory accuracy in older and younger adults. Specifically, we evaluated the effectiveness of item-specific and relational processing instructions relative to a read-only control task on correct and false recognition in younger and older adults using a categorized-list paradigm. In both age groups, item-specific and relational processing improved correct recognition versus a read-only control task, and item-specific encoding decreased false recognition relative to both the relational and read-only groups. This pattern was found in older adults despite overall elevated rates of false recognition. We then applied signal-detection and diffusion-modeling analyses, which separately utilized recognition responses and the latencies to those responses to estimate contributions of encoding and monitoring processes on recognition decisions. Converging evidence from both analyses demonstrated that item-specific processing benefits to memory accuracy were due to improvements of both encoding (estimates of d′ and drift rate) and monitoring (estimates of lambda and boundary separation) processes, and, importantly, occurred similarly in both younger and older adults. Thus, older and younger adults showed similar encoding-based and test-based benefits of item-specific processing to enhance memory accuracy. © 2018 Psychonomic Society, Inc.

Author Keywords
Diffusion modeling;  Distinctiveness;  Item-specific processing;  Relational processing;  Signal detection

Document Type: Article in Press
Source: Scopus

"Correction: First results on survival from a large Phase 3 clinical trial of an autologous dendritic cell vaccine in newly diagnosed glioblastoma – J Transl Med., 16, (2018) (142) DOI: 10.1186/s12967-018-1507-6" (2018) Journal of Translational Medicine

Correction: First results on survival from a large Phase 3 clinical trial of an autologous dendritic cell vaccine in newly diagnosed glioblastoma [J Transl Med., 16, (2018) (142)] DOI: 10.1186/s12967-018-1507-6
(2018) Journal of Translational Medicine, 16 (1), art. no. 179, . 

Liau, L.M.a , Ashkan, K.b , Tran, D.D.c , Campian, J.L.d , Trusheim, J.E.e , Cobbs, C.S.f , Heth, J.A.g , Salacz, M.h , Taylor, S.h , D’Andre, S.D.i , Iwamoto, F.M.j , Dropcho, E.J.k , Moshel, Y.A.l , Walter, K.A.m , Pillainayagam, C.P.n , Aiken, R.o , Chaudhary, R.p , Goldlust, S.A.q , Bota, D.A.r , Duic, P.s , Grewal, J.bg , Elinzano, H.t , Toms, S.A.t , Lillehei, K.O.u , Mikkelsen, T.v , Walbert, T.v , Abram, S.R.w , Brenner, A.J.x , Brem, S.y , Ewend, M.G.z , Khagi, S.z , Portnow, J.aa , Kim, L.J.ab , Loudon, W.G.ac , Thompson, R.C.ad , Avigan, D.E.ae , Fink, K.L.af , Geoffroy, F.J.ag , Lindhorst, S.ah , Lutzky, J.ai , Sloan, A.E.aj , Schackert, G.ak , Krex, D.ak , Meisel, H.-J.al , Wu, J.am , Davis, R.P.an , Duma, C.ao , Etame, A.B.ap , Mathieu, D.aq , Kesari, S.ar , Piccioni, D.ar , Westphal, M.as , Baskin, D.S.at , New, P.Z.at , Lacroix, M.au , May, S.-A.av , Pluard, T.J.aw , Tse, V.ax , Green, R.M.ay , Villano, J.L.az , Pearlman, M.ba , Petrecca, K.bb , Schulder, M.bc , Taylor, L.P.bd , Maida, A.E.bf , Prins, R.M.a , Cloughesy, T.F.a , Mulholland, P.be , Bosch, M.L.bf

a University of California Los Angeles (UCLA) David Geffen School of Medicine, Jonsson Comprehensive Cancer Center, Los Angeles, CA, United States
b King’s College London School of Medical Education, London, United Kingdom
c University of Florida, Gainesville, FL, United States
d Washington University, St. Louis, MO, United States
e Abbott Northwestern Hospital, Minneapolis, MN, United States
f Swedish Neuroscience Institute, Swedish Medical Center, Seattle, WA, United States
g University of Michigan Medical School, Ann Arbor, MI, United States
h University of Kansas Cancer Center, Kansas City, KS, United States
i Sutter Institute for Medical Research, Sacramento, CA, United States
j Columbia University Medical Center, New York, NY, United States
k Indiana University Simon Cancer Center, Indianapolis, IN, United States
l Overlook Medical Center, Summit, NJ, United States
m University of Rochester Medical Center, Rochester, NY, United States
n Rush University Medical Center, Rochester, United States
o Rutgers Cancer Institute, New Brunswick, NJ, United States
p University of Cincinnati Medical Center, Cincinnati, OH, United States
q Hackensack University Medical Center, Hackensack, NJ, United States
r UC Irvine Medical Center, Irvine, CA, United States
s Winthrop-University Hospital, Mineola, NY, United States
t Rhode Island Hospital, Providence, RI, United States
u University of Colorado Hospital, Aurora, CO, United States
v Henry Ford Health System, Detroit, MI, United States
w St. Thomas Research Institute, Nashville, TN, United States
x University of Texas Health Science Center, San Antonio, TX, United States
y University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, United States
z University of North Carolina, Chapel Hill, NC, United States
aa City of Hope National Medical Center, Duarte, CA, United States
ab Thomas Jefferson University, Philadelphia, PA, United States
ac St. Joseph Hospital, Newport Beach, CA, United States
ad Vanderbilt University, Nashville, TN, United States
ae Beth Israel Deaconess Medical Center, Boston, MA, United States
af Baylor University Medical Center, Dallas, TX, United States
ag Illinois CancerCare, Peoria, IL, United States
ah Medical University of South Carolina, Charleston, SC, United States
ai Mount Sinai Comprehensive Cancer Center, Miami, FL, United States
aj University Hospitals Case Medical Center, Cleveland, OH, United States
ak University Hospital Carl-Gustav-Carus of Technical University, Dresden, Germany
al BG-Klinikum Bergmannstrost, Halle, Germany
am Tufts University School of Medicine, Boston, MA, United States
an Stony Brook University, Stony Brook, NY, United States
ao Hoag Cancer Center, Newport Beach, CA, United States
ap H. Lee Moffit Cancer Center and Research Institute, Tampa, FL, United States
aq CHUSHopital Fleurimont, Sherbrooke University, Sherbrooke, QC, Canada
ar UCSD Health System, UC San Diego, San Diego, CA, United States
as Neurochirurgische Klinik University Clinic Hamburg-Eppendorf, Hamburg, Germany
at Houston Methodist, Houston, TX, United States
au Geisinger Health System, Danville, PA, United States
av Klinikum Chemnitz GGMBH, Chemnitz, Germany
aw Saint Luke’s Cancer Institute, Kansas City, MO, United States
ax Kaiser Permanente Northern California, Redwood City, CA, United States
ay Kaiser Permanente Southern California, Los Angeles, CA, United States
az University of Kentucky College of Medicine, Lexington, KY, United States
ba Colorado Neurological Institute, Englewood, CO, United States
bb Montreal Neurological Institute and Hospital, McGill University, Montreal, Canada
bc Northwell Hofstra School of Medicine, Lake Success, NY, United States
bd University of Washington, Department of Neurology, Alvord Brain Tumor Center, Seattle, WA, United States
be University College Hospitals, London, United Kingdom
bf Northwest Biotherapeutics Inc., Bethesda, MD, United States
bg NYU Winthrop Hospital, Mineola, NY, United States

Abstract
Following publication of the original article [1], the authors reported an error in the spelling of one of the author names. In this Correction the incorrect and correct author names are indicated and the author name has been updated in the original publication. The authors also reported an error in the Methods section of the original article. In this Correction the incorrect and correct versions of the affected sentence are indicated. The original article has not been updated with regards to the error in the Methods section. © 2018 The Author(s).

Document Type: Erratum
Source: Scopus

"The role of multiple-choice tests in increasing access to difficult-to-retrieve information" (2018) Journal of Cognitive Psychology

The role of multiple-choice tests in increasing access to difficult-to-retrieve information
(2018) Journal of Cognitive Psychology, pp. 1-12. Article in Press. 

Little, J.L.a b c

a Department of Psychology, California State University, East Bay, Hayward, CA, USA
b Department of Psychology, Hillsdale College, Hillsdale, MI, USA
c Department of Psychology, Washington University in St. Louis, Louis, MO, USA

Abstract
Answering multiple-choice questions improves access to otherwise difficult-to-retrieve knowledge tested by those questions. Here, I examine whether multiple-choice questions can also improve accessibility to related knowledge that is not explicitly tested. In two experiments, participants first answered challenging general knowledge (trivia) multiple-choice questions containing competitive incorrect alternatives and then took a final cued-recall test with those previously tested questions and new related questions for which a previously incorrect answer was the correct answer. In Experiment 1, participants correctly answered related questions more often and faster when they had taken a multiple-choice test than when they had not. In Experiment 2, I showed that the more accurate and faster responses were not simply a result of previous exposure to those alternatives. These findings have practical implications for potential benefits of multiple-choice testing and implications for the processes that occur when individuals answer multiple-choice questions. © 2018 Informa UK Limited, trading as Taylor & Francis Group

Author Keywords
learning;  marginal knowledge;  multiple-choice;  retrieval-practice;  Testing effects

Document Type: Article in Press
Source: Scopus

"Correction to: Bayesian active probabilistic classification for psychometric field estimation" (2018) Attention, Perception, and Psychophysics

Correction to: Bayesian active probabilistic classification for psychometric field estimation
(2018) Attention, Perception, and Psychophysics, p. 1. Article in Press. 

Song, X.D., Sukesan, K.A., Barbour, D.L.

Laboratory of Sensory Neuroscience and Neuroengineering, Department of Biomedical Engineering, Washington University in St. Louis, 1 Brookings Drive, Box 1097, St. Louis, MO, United States

Abstract
The original version of this article neglected to mention a conflict of interest. DLB has a patent pending on technology described in this manuscript. © 2018 The Psychonomic Society, Inc.

Document Type: Article in Press
Source: Scopus

"Longitudinal hearing loss in Wolfram syndrome" (2018) Orphanet Journal of Rare Diseases

Longitudinal hearing loss in Wolfram syndrome
(2018) Orphanet Journal of Rare Diseases, 13 (1), art. no. 102, . 

Karzon, R.a b , Narayanan, A.c , Chen, L.d , Lieu, J.E.C.e , Hershey, T.c f

a Saint Louis Children’s Hospital, One Children’s Place, St. Louis, MO, United States
b Program in Audiology and Communication Sciences, Washington University, St. Louis School of Medicine, St. Louis, MO, United States
c Department of Psychiatry, Washington University, St. Louis School of Medicine, 4525 Scott Avenue, Campus Box 8134, St. Louis, MO, United States
d Division of Biostatistics, Washington University, St. Louis School of Medicine, St. Louis, MO, United States
e Department of Otolaryngology-Head and Neck Surgery, Washington University, St. Louis School of Medicine, St. Louis, MO, United States
f Department of Radiology, Washington University, St. Louis School of Medicine, 4525 Scott Avenue, Campus Box 8134, St. Louis, MO, United States

Abstract
Background: Wolfram syndrome (WFS) is a rare autosomal recessive disease with clinical manifestations of diabetes mellitus (DM), diabetes insipidus (DI), optic nerve atrophy (OA) and sensorineural hearing loss (SNHL). Although SNHL is a key symptom of WFS, there is limited information on its natural history using standardized measures. Such information is important for clinical care and determining its use as an outcome measure in clinical trials. Methods: Standardized audiologic measures, including pure-tone testing, tympanometry, speech perception, and the unaided Speech Intelligibility Index (SII) were assessed in patients with confirmed WFS annually. Mixed model analyses were used to examine main effects of age, time or interactions for pure tone average (PTA), high frequency average (HFA) and SII. Results: Forty WFS patients were evaluated between 1 and 6 times. Mean age at initial enrollment was 13.5 years (SD = 5.6). Patients were classified as having normal hearing (n = 10), mild-to-severe (n = 24) or profound SNHL (n = 6). Mean age of diagnosis for SNHL was 8.3 years (SD = 5.1) with 75% prevalence. HFA worsened over time for both ears, and SII worsened over time in the worse ear, with greater decline in both measures in younger patients. Average estimated change over 1 year for all measures was in the subclinical range and power analyses suggest that 100 patients would be needed per group (treatment vs. placebo) to detect a 60% reduction in annual change of HFA over 3 years. If trials focused on just those patients with SNHL, power estimates suggest 55 patients per group would be sufficient. Conclusions: Most patients had a slow progressive SNHL emerging in late childhood. Change over time with standard audiologic tests (HFA, SII) was small and would not be detectable for at least 2 years in an individual. Relatively large sample sizes would be necessary to detect significant impact on hearing progression in a clinical trial. Hearing function should be monitored clinically in WFS to provide appropriate intervention. Because SNHL can occur very early in WFS, audiologists and otolaryngologists should be aware of and refer for later emerging symptoms. © 2018 The Author(s).

Author Keywords
Hearing loss;  Speech intelligibility index;  Wolfram syndrome

Document Type: Article
Source: Scopus

"The immune-related microRNA miR-146b is upregulated in glioblastoma recurrence" (2018) Oncotarget

The immune-related microRNA miR-146b is upregulated in glioblastoma recurrence
(2018) Oncotarget, 9 (49), pp. 29036-29046. 

Khwaja, S.S.a , Cai, C.b , Badiyan, S.N.c , Wang, X.d , Huang, J.d

a Department of Neurosurgery, UTHealth McGovern School of Medicine, Mischer Neuroscience Associates, Houston, TX, United States
b Department of Pathology, UT Southwestern Medical Center, Dallas, TX, United States
c Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD, United States
d Department of Radiation Oncology, Washington University School of Medicine, St.Louis, MO, United States

Abstract
Background: Glioblastoma (GBM) has a high rate of local recurrence despite chemoradiotherapy (CRT). Genome-wide expression profiling was performed on patient tumors before and after chemoradiotherapy to identify genes and gene pathways associated with recurrence. Results: Median time to recurrence was 8.9 months with median time to second surgery of 9.6 months. The microRNA (miRNA) analysis identified 9 oncologic and immune-related miRNAs to be differentially expressed, including the hypoxia-related miR-210 and the immune-modulatory miR-146b. More than 1200 differentiallyexpressed genes were identified with RNA-sequencing (RNA-seq). Gene set enrichment analysis (GSEA) identified p53 signaling, Notch, Wnt, VEGF, and MEK gene sets enriched in recurrent GBM. Consistent with the miRNA profiling data, the miR-146b target gene set from GSEA analysis was also associated with recurrence. Methods: Fourteen patients with GBM recurrence after CRT who had available tumor tissue from the initial diagnosis as well as recurrence were selected. Total RNA was isolated from formalin-fixed paraffin-embedded (FFPE) tumor specimens. Genome-wide expression profiling using RT-PCR for miRNA analysis and RNA-seq for messenger RNA (mRNA) analysis were conducted to identify differentially-expressed genes. GSEA was performed on the differential expression data. Conclusions: Genome-wide expression profiling identifies multiple oncologic and immune-related gene sets associated with GBM recurrence. In particular, immunerelated miR-146b is upregulated in recurrence and deserves further investigation. ©Khwaja et al.

Author Keywords
GBM;  Gene expression profiling;  Glioma;  MiR-146b;  Recurrence

Document Type: Article
Source: Scopus

"Analysis of shared heritability in common disorders of the brain" (2018) Science

Analysis of shared heritability in common disorders of the brain
(2018) Science, 360 (6395), art. no. 8757, . Cited 1 time.

Anttila, V.a b c xn , Bulik-Sullivan, B.a c , Finucane, H.K.b c d e , Walters, R.K.a b c , Bras, J.f g , Duncan, L.a b c h , Escott-Price, V.i j , Falcone, G.J.k l m , Gormley, P.a b c k , Malik, R.n , Patsopoulos, N.A.c o , Ripke, S.a b c p , Wei, Z.q , Yu, D.b k , Lee, P.H.b k , Turley, P.a c , Grenier-Boley, B.r s t , Chouraki, V.r s t u , Kamatani, Y.v w , Berr, C.x y z , Letenneur, L.aa ab , Hannequin, D.ac ad , Amouyel, P.r s t u , Boland, A.ae , Deleuze, J.-F.ae , Duron, E.af ag , Vardarajan, B.N.ah , Reitz, C.ai , Goate, A.M.aj , Huentelman, M.J.ak , Ilyas Kamboh, M.al , Larson, E.B.am an , Rogaeva, E.ao , George-Hyslop, P.S.ao ap , Hakonarson, H.aq ar as , Kukull, W.A.at , Farrer, L.A.au , Barnes, L.L.av aw ax , Beach, T.G.ay , Yesim Demirci, F.al , Head, E.az , Hulette, C.M.ba , Jicha, G.A.bb , Kauwe, J.S.K.bc , Kaye, J.A.bd , Leverenz, J.B.be , Levey, A.I.bf , Lieberman, A.P.bg , Pankratz, V.S.bh , Poon, W.W.bi , Quinn, J.F.bj bk , Saykin, A.J.bl , Schneider, L.S.bm , Smith, 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a Analytic Translational Genetics Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States
b Stanley Center for Psychiatric Research, Broad Institute of mit and Harvard, Cambridge, MA, United States
c Program in Medical and Population Genetics, Broad Institute of mit and Harvard, Cambridge, MA, United States
d Department of Mathematics, Massachusetts Institute of Technology, Cambridge, MA, United States
e Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, United States
f UK Dementia Research Institute, University College London, London, United Kingdom
g Department of Molecular Neuroscience, Institute of Neurology, University College London, London, United Kingdom
h Department of Psychiatry and Behavioral Science, Stanford University, Stanford, CA, United States
i Cardiff University, Medical Research Council Center for Neuropsychiatric Genetics and Genomics, Institute of Psychology, Medicine and Clinical Neuroscience, Cardiff, United Kingdom
j Dementia Research Institute, Cardiff University, Cardiff, United Kingdom
k Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, United States
l Department of Neurology, Massachusetts General Hospital, Boston, MA, United States
m Harvard Medical School, Boston, MA, United States
n Institute for Stroke and Dementia Research (ISD), University Hospital, LMU Munich, Munich, Germany
o Department of Neurology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, United States
p Charite Universitatsmedizin Berlin, Berlin, Germany
q Department of Computer Science, New Jersey Institute of Technology, New Jersey, United States
r INSERM U1167 LabEx DISTALZ, Lille, France
s Institut Pasteur de Lille, Lille, France
t Université de Lille, U1167, RID-AGE, Risk Factors and Molecular Determinants of Aging-Related Diseases, Lille, France
u Centre Hosp, Univ Lille, Lille, France
v Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
w Center for Genomic Medicine, Kyoto University, Graduate School of Medicine, Kyoto, Japan
x INSERM U1061 – Neuropsychiatry: Epidemiological and Clinical Research, Montpellier, France
y University of Montpellier, Montpellier, France
z Memory Research and Resources Center, Department of Neurology, Montpellier University Hospital Gui de Chauliac, Montpellier, France
aa INSERM, UMR 1219, Bordeaux, France
ab University of Bordeaux, Bordeaux, France
ac Rouen University Hospital, Rouen, France
ad Inserm U1245, Rouen, France
ae Centre National de Recherche en Génomique Humaine (CNRGH), Institut de biologie François Jacob, CEA, Evry, France
af Department of Gerontology, Hôpital Broca, AH-HP, Paris, France
ag Hôpital Paul Brousse Université Paris Sud XI, Le Kremlin-Bicêtre, Paris, France
ah Gertrude H. Sergievsky Center, Dept of Neurology, Columbia University, New York, NY, United States
ai Columbia University, New York, NY, United States
aj Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, United States
ak Translational Genomics Research Institute, Neurogenomics Division, Phoenix, AZ, United States
al University of Pittsburgh, Pittsburgh, PA, United States
am Kaiser Permanente Washington Health Research Institute, Seattle, WA, United States
an Department of Medicine, University of WashingtonWA, United States
ao Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, Canada
ap Cambridge Institute for Medical Research, University of Cambridge, Cambridge, United Kingdom
aq Center for Applied Genomics of The Children’s Hospital of Philadelphia, Philadelphia, PA, United States
ar Division of Human Genetics, Children’s Hospital of Philadelphia, Philadelphia, PA, United States
as Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States
at National Alzheimer Coordinating Center (NACC), Department of Epidemiology, University of Washington, Seattle, WA, United States
au Department of Medicine, Boston University, School of Medicine, Boston, MA, United States
av Rush Alzheimers Disease Center, Chicago, IL, United States
aw Department of Neurological Sciences, Rush Medical College, Chicago, IL, United States
ax Department of Behavioral Sciences, Rush Medical College, Chicago, IL, United States
ay Banner Sun Health Research Institute, Sun City, AZ, United States
az Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, United States
ba Department of Pathology, Duke University, School of Medicine, Durham, NC, United States
bb College of Medicine, University of Kentucky, Lexington, KY, United States
bc Department of Biology, Brigham Young University, Provo, UT, United States
bd Layton Aging and Alzheimer’s Disease Center, Oregon Health and Science University, Portland, OR, United States
be Lou Ruvo Center for Brain Health, Neurological Institute, Cleveland Clinic, Cleveland, OH, United States
bf Department of Neurology, School of Medicine, Emory University, Atlanta, GA, United States
bg Department of Pathology, University of Michigan Medical School, Ann Arbor, MI, United States
bh University of New Mexico Health Sciences Center, Albuquerque, NM, United States
bi Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, CA, United States
bj Department of Neurology, Oregon Health and Science University, Portland, OR, United States
bk Department of Neurology and Parkinson’s Disease Research Education and Clinical Care Center (PADRECC), Portland Veterans Affairs Medical Center, Portland, OR, United States
bl Indiana Alzheimer Disease Center, Indiana University, School of Medicine, Indianapolis, IN, United States
bm Keck School of Medicine of the, University of Southern California, Los Angeles, CA, United States
bn Byrd Alzheimer’s Institute, University of South Florida, Tampa, FL, United States
bo Department of Pathology, University of Utah, Salt Lake City, UT, United States
bp Department of Pathology, University of Washington, Seattle, WA, United States
bq Boston University, School of Medicine, Boston, MA, United States
br Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States
bs School of Biotechnology, Dublin City University, Glasnevin, Dublin, Ireland
bt Functional Genomics Center Zurich, ETH/UZH-Zurich, Zurich, Switzerland
bu Department of Medical Genetics, Cambridge Institute for Medical Research, Cambridge, United Kingdom
bv UK Dementia Research Institute, Cambridge, United Kingdom
bw School of Medicine, Cardiff University, Cardiff, United Kingdom
bx 1st and 3rd Departments of Neurology, Aristotle University of Thessaloniki, Thessaloniki, Greece
by Greek Association of Alzheimer’s Disease and Related Disorders, Thessaloniki, Greece
bz Maurice Wohl Clinical Neuroscience Institute, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, United Kingdom
ca Dementia Research Centre, UCL Institute of Neurology, London, United Kingdom
cb Sorbonne University, GRC n° 21, Alzheimer Precision Medicine (APM), AP-HP, Pitié-Salpêtrière Hospital, Paris, France
cc Institute of Memory and Alzheimer’s Disease (IM2A), Department of Neurology, Pitié-Salpêtrière Hospital, AP-HP, Paris, France
cd Brain and Spine Institute (ICM), INSERM U 1127, CNRS UMR 7225, Paris, France
ce AXA Research Fund and Sorbonne University Chair, Paris, France
cf MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, United Kingdom
cg Institute of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff, United Kingdom
ch Institute of Prion Diseases and MRC Prion Unit, University College London, London, United Kingdom
ci Centre for Public Health, Queens University Belfast, Belfast, United Kingdom
cj Human Genetics, School of Life Sciences, University of Nottingham, Nottingham, United Kingdom
ck Department of Genomics, Life and Brain Center, University of Bonn, Bonn, Germany
cl Institute of Human Genetics, School of Medicine, University of Bonn, University Hospital Bonn, Bonn, Germany
cm Department of Neurodegeneration, UCL Institute of Neurology, London, United Kingdom
cn QIMR Berghofer Medical Research Institute, Brisbane, Australia
co Institute of Psychiatry Psychology and Neuroscience, Kings College London, United Kingdom
cp Institute of Medical Genetics and Pathology, University Hospital Basel, Basel, Switzerland
cq Human Genomics Research Group, Department of Biomedicine, University of Basel, Basel, Switzerland
cr Department of Psychiatry and Psychotherapy, Friedrich-Alexander-Universität Erlangen-Nürnberg University Hospital, Erlangen, Germany
cs Department of Psychiatry and Global Brain Health Institute, Trinity College, Dublin, Ireland
ct Division of Psychiatry, Molecular Psychiatry Laboratory, University College London, London, United Kingdom
cu Maurice Wohl Clinical Neuroscience Institute, Department of Basic and Clinical Neuroscience, King’s College London, London, United Kingdom
cv King’s College Hospital, London, United Kingdom
cw Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, United States
cx Fundació ACE, Institut Català de Neurociències Aplicades, Barcelona, Spain, Universitat Internacional de Catalunya, Barcelona, Spain
cy Facultat de Medicina i Ciències de la Salut, Universitat Internacional de Catalunya (UIC), Barcelona, Spain
cz Glenn Biggs Institute for Alzheimer’s and Neurodegenerative Diseases, University of Texas Health Sciences Center, San Antonio, TX, United States
da Neurology and Neurogenetics Core, Framingham Heart Study, Framingham, MA, United States
db School of Medicine, Boston University, Boston, MA, United States
dc School of Public Health, Boston University, Boston, MA, United States
dd Framingham Heart Study, Framingham, MA, United States
de Department of Biostatistics, University of Washington, Seattle, WA, United States
df Department of Epidemiology, Erasmus Medical Centre, Rotterdam, Netherlands
dg Center for Translational and Computational Neuroimmunology, Columbia University Medical Center, New York, NY, United States
dh Neurogenetics Program, Departments of Neurology and Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, United States
di Center For Autism Research and Treatment, Semel Institute, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, United States
dj Institute for Precision Health, University of California, Los Angeles, Los Angeles, CA, United States
dk Department of Psychiatry, Saarland University Hospital, Homburg, Germany
dl Institute of Social Medicine, Occupational Health and Public Health (ISAP), University of Leipzig, Leipzig, Germany
dm Institute for Translational Genomics and Population Sciences, Departments of Pediatrics and Medicine, LABioMed at Harbor-UCLA Medical Center, Torrance, CA, United States
dn Department of Neurology II, Kepler University Clinic, Johannes Kepler University, Linz, Austria
do Massachusetts General Hospital, Boston, MA, United States
dp Washington University, School of Medicine, St. Louis, MO, United States
dq Communication and Research Unit for Musculoskeletal Disorders (FORMI), Oslo University Hospital, Oslo, Norway
dr Department of Neurology, Oslo University Hospital, Oslo, Norway
ds Institute for Molecular Medicine Finland (FIMM), HiLIFE, University of Helsinki, Helsinki, Finland
dt Estonian Genome Center, Institute of Genomics, University of Tartu, Tartu, Estonia
du Illumina Inc., San Diego, CA, United States
dv 23andMe Inc., Mountain View, CA, United States
dw Institute of PublicHealth, Charité – Universitätsmedizin Berlin, Berlin, Germany
dx Department of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam, Netherlands
dy Department of Neurology, Leiden University Medical Center, Leiden, Netherlands
dz Institute for Stroke and Dementia Research, Klinikum der Universitaet Muenchen, Munich, Germany
ea Department of Neurology and Epileptology, Hertie Institute for Clinical Brain Research, University of Tuebingen, Tuebingen, Germany
eb Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden
ec Institute of Human Genetics, University of Ulm, Ulm, Germany
ed Department of Radiology and Nuclear Medicine, Erasmus Medical Centre, Rotterdam, Netherlands
ee Department of Clinical Chemistry, Fimlab Laboratories, Finnish Cardiovascular Research Center-Tampere, Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland
ef Department of Ophthalmology, University of Helsinki, Helsinki University Hospital, Helsinki, Finland
eg Department of Public Health, University of Helsinki, Helsinki, Finland
eh Brigham and Women’s Hospital, Boston, MA, United States
ei Department of Neurology, University Hospital Essen, Germany
ej Landspitali National University Hospital, Reykjavik, Iceland
ek Avera Institute for Human Genetics, Sioux Falls, SD, United States
el Department of Psychiatry, VU University Medical Center, Amsterdam, Netherlands
em Department of Neurology, Helsinki University Central Hospital, Helsinki, Finland
en Institute for Molecular Bioscience, University of Queensland, Brisbane, Australia
eo Department of Medicine, Harvard Medical School, Boston, MA, United States
ep Boston VA Research Institute, Boston, MA, United States
eq Brigham Women’s Hospital, Division of Aging, Harvard Medical School, Boston, MA, United States
er Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, United Kingdom
es Max Planck Institute of Psychiatry, Munich, Germany
et Munich Cluster for Systems Neurology (SyNergy), Munich, Germany
eu Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom
ev Institute of Clinical Molecular Biology, Kiel University, University Hospital Schleswig-Holstein, Kiel, Germany
ew Clinic of Internal Medicine I, University Hospital Schleswig-Holstein, Kiel, Germany
ex National Institute for Health and Welfare, Helsinki, Finland
ey Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, United States
ez Kiel Pain and Headache Center, Kiel, Germany
fa Pediatric Neurology Research Group, Vall d’Hebron Research Institute, Autonomous University of Barcelona, Barcelona, Spain
fb Headache Unit, Neurology Department, Hospital Vall d’Hebron, Barcelona, Spain
fc Headache Research Group, VHIR, Autonomous University of Barcelona, Barcelona, Spain
fd Danish Headache Center, Rigshospitalet Glostrup and University of Copenhagen, Copenhagen, Denmark
fe Institute of Biological Psychiatry, Roskilde, Denmark
ff Department of Clinical Sciences, University of Copenhagen, Copenhagen, Denmark
fg Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus, Denmark
fh Institute of Human Genetics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
fi Department of Human Genetics, Leiden University Medical Center, Leiden, Netherlands
fj Division of Clinical Neuroscience, Oslo University Hospital, University of Oslo, Oslo, Norway
fk Netherlands Twin Register, Vrije Universiteit, Amsterdam, Netherlands
fl Division of Preventive Medicine, Brigham and Women’s Hospital, Boston, MA, United States
fm Statistical and Genomic Epidemiology Laboratory, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, QLD, Australia
fn Department of Clinical and Experimental Epilepsy, UCL Institute of Neurology, London, United Kingdom
fo Centre for Genomic Sciences, University of Hong Kong, Hong Kong, Hong Kong
fp Epilepsy Research Centre, University of Melbourne, Heidelberg, Australia
fq Quantinuum Research LLC, San Diego, CA, United States
fr Cooper Medical School, Rowan University, Camden, NJ, United States
fs Thomas Jefferson University Hospital, Philadelphia, PA, United States
ft Children’s Hospital of Philadelphia, Philadelphia, PA, United States
fu Epilepsy Society, Chalfont-St-Peter, Bucks, United Kingdom
fv Centre de Recherche du Centre Hospitalier de l’Universite de Montreal, Department of Neurosciences, Université de Montréal, Montréal, Canada
fw Neurogenetics Group, VIB-CMN, Antwerp, Belgium
fx University of Antwerp, Antwerp, Belgium
fy Department of Neurology, Antwerp University Hospital, Antwerp, Belgium
fz Department of Neurology, Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium
ga Division of Neurology, Children’s Hospital of Philadelphia, Philadelphia, PA, United States
gb Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States
gc Department of Biomedical Sciences, Cooper Medical School, Rowan University, Camden, NJ, United States
gd Department of Psychiatry, Center for Neurobiology and Behavior, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States
ge NYU School of Medicine, New York, NY, United States
gf Amplexa Genetics A/S, Odense, Denmark
gg Institute of Mental Health, University of Nottingham, Nottingham, United Kingdom
gh Epilepsy Center/ Neurocenter, Kuopio University Hospital, Kuopio, Finland
gi Institute of Clinical Medicine, School of Medicine, Faculty of Health Sciences, University of Eastern Finland, Kuopio, Finland
gj Department of Epileptology, University Bonn Medical Center, Bonn, Germany
gk Institute of Experimental Epileptology and Cognition Research, University Bonn Medical Center, Bonn, Germany
gl Department of Clinical and Experimental Epilepsy, NIHR University College London Hospitals, Biomedical Research Centre, UCL Institute of Neurology, London, United Kingdom
gm Department of Genetics, University Medical Center Utrecht, Netherlands
gn Epilepsy Foundation in the Netherlands (SEIN), Heemstede, Netherlands
go Departments of Pediatrics and Neurology, Ohio State University, Columbus, OH, United States
gp Nationwide Children’s Hospital, Columbus, OH, United States
gq Department of Neurology, University of California, San Francisco, CA, United States
gr Department of Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, Dublin, Ireland
gs Center for Molecular Medicine, University Medical Center Utrecht, Utrecht, Netherlands
gt Danish Epilepsy Centre, Filadelfia, Dianalund, Denmark
gu Institute for Regional Health Services, University of Southern Denmark, Odense, Denmark
gv Trinity College Dublin, Dublin, Ireland
gw United Christian Hospital, Hong Kong
gx Hong Kong Sanatorium and Hospital, Hong Kong
gy Epilepsy Research Centre, University of Melbourne, Austin Health, Heidelberg, Australia
gz Department of Neurology, University of Cincinnati, Cincinnati, OH, United States
ha UC Gardner Neuroscience Institute, Cincinnati, OH, United States
hb Department of Neurology, Duke University, School of Medicine, Durham, NC, United States
hc Cologne Center for Genomics (CCG), University of Cologne, Cologne, Germany
hd Department of Neurology, Beth Israel Deaconess Medical Center, Boston, MA, United States
he Department of Neurology, Inselspital, Bern University Hospital, University of Bern, Switzerland
hf Department of Neurology, University of Munich Hospital, Grosshadern, University of Munich, Germany
hg Department of Medicine, University of Melbourne, Austin Health, Melbourne, VIC, Australia
hh Department of Paediatrics, Royal Children’s Hospital, University of Melbourne, Melbourne, VIC, Australia
hi Florey Institute of Neuroscience and Mental Health, Melbourne, VIC, Australia
hj Institute of Neuropathology, Bonn University Medical School, Bonn, Germany
hk UCL Institute of Neurology, London, United Kingdom
hl Chalfont Centre for Epilepsy, Bucks, United Kingdom
hm University Hospital of Wales, Cardiff, United Kingdom
hn Department of Neurology, Thomas Jefferson University, Philadelphia, PA, United States
ho Pediatric Neurology and Muscular Diseases Unit, Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, “G. Gaslini” Institute, Genova, Italy
hp Department of Epileptology, University Hospital Bonn, Bonn, Germany
hq Section of Epileptology, Department of Neurology, University Hospital RWTH Aachen, Aachen, Germany
hr Institute of Applied Health Research, University of Birmingham, United Kingdom
hs Department of Neurology, Admiraal De Ruyter Hospital, Goes, Netherlands
ht Laboratory of Neurogenetics, G. Gaslini Institute, Genova, Italy
hu Institute for Genomic Medicine, Columbia University Medical Center, New York, NY, United States
hv University of Liverpool, Liverpool, United Kingdom
hw Walton Centre NHS Foundation Trust, Liverpool, United Kingdom
hx Department of Neurology and Epileptology, University Hospital Tuebingen, Tuebingen, Germany
hy Department of Neurology, University of Ulm, Ulm, Germany
hz CWZ Hospital, Nijmegen, Netherlands
ia Department of Neurology, Medical University of Vienna, Austria
ib Hertie-Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany
ic German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany
id Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, United States
ie INSERM U1220, IRSD, Toulouse, France
if Université Paul Sabatier, Toulouse, France
ig Centre for Genetic Epidemiology, Institute for Clinical Epidemiology and Applied Biometery, University of Tubingen, Germany
ih Division of Life Science, Hong Kong University of Science and Technology, Hong Kong Special Administrative Region, Hong Kong
ii Department of Genetics, Center for Molecular Medicine, University Medical Center Utrecht, Utrecht, Netherlands
ij Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford, United Kingdom
ik University of Lincoln, Lincoln, United Kingdom
il Faculty of Health and Medicine, University of Newcastle, Callaghan, Australia
im University of Newcastle, Callaghan, Australia
in Hunter Medical Research Institute, Newcastle, Australia
io Division of Neurocritical Care and Emergency Neurology, Massachusetts General Hospital, Boston, MA, United States
ip Department of Cerebrovascular Diseases, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milano, Italy
iq PhD Program in Neuroscience, University Milano-Bicocca, Monza, Italy
ir Austin Health, Heidelberg, Australia
is University of Virginia Center for Public Health Genomics, University of Virginia, Charlottesville, VA, United States
it Dept of Medicine, University of Maryland, School of Medicine, Baltimore, MD, United States
iu Geriatrics Research and Education Clinical Center, Baltimore Veterans Administration Medical Center, Baltimore, MD, United States
iv Centre for Prevention of Stroke and Dementia, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom
iw Institute of Cardiovascular Research, Royal Holloway University of London, London, United Kingdom
ix Ashford and St Peters NHS Foundation Trust, Surrey, United Kingdom
iy University of Edinburgh, Edinburgh, United Kingdom
iz Instituto Nacional de Saúde Doutor Ricardo Jorge, Lisboa, Portugal
ja Biosystems and Integrative Sciences Institute – BioISI, University of Lisboa, Lisboa, Portugal
jb Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom
jc Department of Neurology, Jagiellonian University Medical College, Kraków, Poland
jd Warren Alpert Medical School, Brown University, Providence, RI, United States
je Department of Neurology, College of Medicine-Jacksonville, University of Florida, Jacksonville, FL, United States
jf University of Split, School of Medicine, Split, Croatia
jg University of North Carolina at Chapel Hill, Chapel Hill, NC, United States
jh Icahn School of Medicine at Mount Sinai, New York, NY, United States
ji Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom
jj Oxford Centre for Diabetes, Endocrinology and Metabolism, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom
jk Department of Human Genetics, Wellcome Sanger Institute, Hinxton, Cambridgeshire, United Kingdom
jl MRC Social, Genetic and Developmental Psychiatry Centre, King’s College London, London, United Kingdom
jm Genes and Disease Programme, Centre for Genomic Regulation (CRG), Barcelona, Spain
jn Department of Adult Psychiatry, Poznan University of Medical Sciences, Poland
jo Clinicum, Department of Public Health, University of Helsinki, Finland
jp Department of Adolescent Psychiatry, Helsinki University Central Hospital, Helsinki, Finland
jq Harvard Medical School, McLean Hospital, Belmont, MA, United States
jr Norwegian Institute of Public Health, Oslo, Norway
js University of Oslo, Oslo, Norway
jt Department of Medicine, Surgery and Dentistry “Scuola Medica Salernitana”, University of Salerno, Italy
ju Eating Disorders Unit, Department of Child and Adolescent Psychiatry, Medical University of Vienna, Vienna, Austria
jv Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland
jw Kartini Clinic, Portland, OR, United States
jx Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States
jy MRC Integrative Epidemiology Unit, Bristol Medical School, University of Bristol, Bristol, United Kingdom
jz Zorg op Orde BV, Leidschendam, Netherlands
ka Division of Psychological and Social Medicine and Developmental Neurosciences, Faculty of Medicine, Technischen Universität Dresden, Dresden, Germany
kb Department of Child and Adolescent Psychiatry and Psychosomatic Medicine of University Clinics, RWTH Aachen, Aachen, Germany
kc Altrecht Eating Disorders Rintveld, Altrecht Mental Health Institute, Zeist, Netherlands
kd Faculty of Social Sciences, University of Utrecht, Utrecht, Netherlands
ke Medical Genetics Unit, Department SDB, University of Padova, Padova, Italy
kf UOC Genetica ed Epidemiologica Clinica Az. Ospedaliera, Padova, Italy
kg Department of Human Genetics, CHU Sart-Tilman, University of Liège, Liège, Belgium
kh Department of Rheumatology, CHU Sart-Tilman, University of Liège, Liège, Belgium
ki Department of Cancer Epidemiology and Prevention, Cancer Center and M. Sklodowska-Curie Institute of Oncology, Warsaw, Poland
kj Department of Psychiatry, University of Medical Sciences, Poznan, Poland
kk Department of Psychiatry, University of Perugia, Perugia, Italy
kl Department of Mental and Physical Health and Preventive Medicine, University of Campania “luigi Vanvitelli”, Naples, Italy
km Eating Disorders Unit, 1st Psychiatric Department, National and Kapodistrian University of Athens, Athens, Greece
kn Aglaia Kyriakou Childrens Hospital, Athens, Greece
ko Eating Disorders Unit, Department of Psychiatry, First Faculty of Medicine, Charles University, Prague, Czech Republic
kp General University Hospital, Prague, Czech Republic
kq Medical University of Vienna, Austria
kr School of Psychology, Flinders University, Adelaide, Australia
ks Vall d’Hebron Research Institute, Barcelona, Spain
kt Institut de Recerca Sant Joan de Déu, Barcelona, Spain
ku Institut de Biomedicina de la Universitat de Barcelona (IBUB), Barcelona, Spain
kv Department of Genetics, Microbiology and Statistics, Faculty of Biology, University of Barcelona, Barcelona, Spain
kw Centre for Genomic Regulation (CRG), Barcelona, Spain
kx Departments of Psychology and Human and Molecular Genetics, College Behavioral and Emotional Health Institute, Virginia Commonwealth University, Richmond, VA, United States
ky Broad Institute of mit and Harvard, Cambridge, United States
kz NORMENT, Div. of Mental Health and Addiction, University of Oslo, Oslo, Norway
la Oslo University Hospital, Oslo, Norway
lb Department of Psychology, University of Oslo, Norway
lc K. G. Jebsen Centre for Research onNeuropsychiatric Disorders, University of Bergen, Bergen, Norway
ld Department of Biological and Medical Psychology, University of Bergen, Bergen, Norway
le NORMENT, K.G. Jebsen Center for Psychosis Research, Department of Clinical Science, University of Bergen, Norway
lf Department of Medical Genetics, Haukeland University Hospital, Bergen, Norway
lg Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, United States
lh Seaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai, New York, NY, United States
li Department of Genetics and Genomic Sciences, Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY, United States
lj Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, NY, United States
lk McLaughlin Centre, Department of Molecular Genetics, University of Toronto, Toronto, Canada
ll Centre for Applied Genomics, Hospital for Sick Children, Toronto, Canada
lm Biopsychosocial Corporation, Vienna, Austria
ln Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria
lo Zentren für Seelische Gesundheit, BBRZ-Med, Vienna, Austria
lp Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
lq Rheumatology Unit, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Solna, Sweden
lr Weill Cornell Medical College, New York, NY, United States
ls School of Medicine, University of North Dakota, Grand Forks, ND, United States
lt Neuropsychiatric Research Institute, Fargo, ND, United States
lu Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, United States
lv BioRealm, Walnut, CA, United States
lw Oregon Research Institute, Eugene, OR, United States
lx Department of Psychiatry, University of California San Diego, San Diego, CA, United States
ly Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, Madrid, Spain
lz Department of Psychiatry, Hospital Universitari Vall d’Hebron, Barcelona, Spain
ma Psychiatric Genetics Unit, Group of Psychiatry, Mental Health and Addiction, Vall d’Hebron Research Institute (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain
mb Department of Psychiatry and Legal Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain
mc Biomedical Network Research Centre on Mental Health (CIBERSAM), Instituto de Salud Carlos III, Madrid, Spain
md Universitat Autònoma de Barcelona, Barcelona, Spain
me Programa Corporatiu “Neurodevelopment Disorders along Life Span”, Institut Català de la Salut, Barcelona, Spain
mf Clinica Galatea y PAIMM, Mental Health Program for Impaired Physicians, Barcelona, Spain
mg Child and Adolescent Mental Health Unit, Hospital Universitario Mútua de Terrassa, Barcelona, Spain
mh Fundació Docència i Recerca Mútua Terrassa, Canada
mi K.G. Jebsen Centre for Neuropsychiatric Disorders, Department of Biomedicine, University of Bergen, Norway
mj Division of Psychiatry, Haukeland University Hospital, Bergen, Norway
mk K.G. Jebsen Centre for Neuropsychiatric Disorders, Department of Clinical Science, University of Bergen, Norway
ml Institute of Medical Informatics and Statistics, Kiel University, Kiel, Germany
mm Child and Adolescent Psychiatry/Psychotherapy, University Medical Center, Goettingen, Germany
mn Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, United Kingdom
mo Clinic for Child and Adolescent Psychiatry and Psychotherapy, University of Duisburg-Essen, Essen, Germany
mp Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany
mq Department of Human Genetics, Radboud University Medical Center, Nijmegen, Netherlands
mr Department of Psychiatry, Radboud University Medical Center, Nijmegen, Netherlands
ms Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, Netherlands
mt Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behavior, Radboud University Medical Centre, Nijmegen, Netherlands
mu Karakter Child and Adolescent Psychiatry University Center, Nijmegen, Netherlands
mv Department of Psychiatry and Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, Netherlands
mw Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt, Frankfurt am Main, Germany
mx Laboratory of Psychiatric Neurobiology, Institute of Molecular Medicine, I.M. Sechenov First Moscow State Medical University, Moscow, Russian Federation
my Department of Translational Psychiatry, School for Mental Health and Neuroscience (MHeNS), Maastricht University, Maastricht, Netherlands
mz Division of Molecular Psychiatry, Center of Mental Health, University of Wuerzburg, Wuerzburg, Germany
na Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University Hospital Frankfurt, Goethe University, Frankfurt am Main, Germany
nb Center of Mental Health, Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University Hospital of Wuerzburg, Wuerzburg, Germany
nc School of Psychology, Cardiff University, United Kingdom
nd Central Institute of Mental Health, Department of Genetic Epidemiology in Psychiatry, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany
ne National Centre for Register-based Research, Aarhus University, Aarhus, Denmark
nf Hospital of Telemark, Kragerø, Norway
ng Department of Biomedicine and Human Genetics, Aarhus University, Aarhus, Denmark
nh Center for Integrative Sequencing (iSEQ), Aarhus University, Aarhus, Denmark
ni Aarhus Genome Center, Aarhus, Denmark
nj Department of Psychology, Emory University, Atlanta, GA, United States
nk Department of Medical Informatics and Clinical Epidemiology, Oregon Health and Science University, Portland, OR, United States
nl Department of Psychological and Brain Sciences, University of Iowa, Iowa City, IA, United States
nm Departamento de Genética, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil
nn ADHD Outpatient Clinic, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil
no Neurosciences and Mental Health Program, Research Institute, Hospital for Sick Children, Toronto, Canada
np University of Toronto, Toronto, Canada
nq Hospital for Sick Children, Toronto, Canada
nr Department of Psychiatry, University of California, Los Angeles, Los Angeles, CA, United States
ns Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, United States
nt Department of Psychiatry, Faculdade de Medicina, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil
nu Department of Psychiatry, University of California, San Francisco, San Francisco, CA, United States
nv Institute for Human Genetics, University of California, San Francisco, San Francisco, CA, United States
nw Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, United States
nx Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy
ny Department of Psychiatry, University of British Columbia, Vancouver, Canada
nz Institute of Mental Health, University of British Columbia, Vancouver, Canada
oa Stella Maris Clinical Research Institute for Child and Adolescent Neuropsychiatry, Pisa, Italy
ob Sorbonne Université, INSERM, CNRS, Neuroscience Paris Seine, Institut de Biologie Paris Seine, Paris, France
oc NIHR Biomedical Research Centre in Mental Health Maudsley Hospital, London, United Kingdom
od Department of Human Genetics, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, United States
oe LifeOmic, Indianapolis, IN, United States
of Department of Psychiatry and Behavioral Sciences, Duke University, Durham, NC, United States
og University Clinic of Pediatrics, Faculty of Medicine, University of Coimbra, Coimbra, Portugal
oh Child Developmental Center, Hospital Pediátrico, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal
oi Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, NY, United States
oj Dept of Clinical Genetics, Our Lady’s Children’s Hospital, Crumlin, Dublin, Ireland
ok School of Medicine and Medical Science, University College Dublin, Dublin, Ireland
ol Division of Molecular Genome Analysis, Division of Cancer Genome Research, German Cancer Research Center (DKFZ), Heidelberg, Germany
om Inserm U955, Psychiatrie Translationnelle, Créteil, France
on Faculté de Médecine, Université Paris Est, Créteil, France
oo Fondation FondaMental, Créteil, France
op Children’s Hospital Los Angeles, Los Angeles, CA, United States
oq Yale Center for Genome Analysis, Yale University, New Haven, CT, United States
or Department of Genetics, Yale University, School of Medicine, New Haven, CT, United States
os Division of Child and Adolescent Psychiatry, Department of Psychiatry and Human Behavior, Brown University, Providence, RI, United States
ot Institute of Neuroscience, Newcastle University, Newcastle, United Kingdom
ou Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle, United Kingdom
ov Northumberland, Tyne and Wear NHS Foundation Trust, Northumberland, United Kingdom
ow Genomics Medicine Ireland, Dublin, Ireland
ox Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
oy Department of Psychiatry, Hospital for Sick Children, University of Toronto, Toronto, Canada
oz Program in Genetics and Genome Biology, Hospital for Sick Children, Toronto, Canada
pa Department of Psychiatry, Carver College of Medicine, University of Iowa, Iowa City, IA, United States
pb Division of Medical Genetics, Department of Medicine, University of Washington, Seattle, WA, United States
pc Department of Psychiatry, University of Illinois at Chicago, Chicago, IL, United States
pd Center for Psychiatric Research, Maine Medical Center Research Institute, Portland, ME, United States
pe Department of Psychiatry, Tufts University, School of Medicine, Boston, MA, United States
pf Child and Adolescent Psychiatry Department, Robert Debre Hospital, APHP, Paris, France
pg Human Genetics and Cognitive Functions, Institut Pasteur, Paris, France
ph Centre d’Etudes et de Recherches en Psychopathologie et Psychologie de la Santé (CERPPS), Université Toulouse Jean Jaurès, Toulouse, France
pi CERESA, Toulouse, France
pj Institut Universitaire de France, Paris, France
pk Academic Centre on RareDiseases University College Dublin (ACoRD/UCD), Dublin, Ireland
pl McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University, School of Medicine, Baltimore, MD, United States
pm Institute of Psychiatric Phenomics and Genomics (IPPG), University Hospital, LMU Munich, Munich, Germany
pn Department of Psychiatry and Psychotherapy, University Medical Center Göttingen, Göttingen, Germany
po Department of Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, MD, United States
pp Human Genetics Branch, National Institute of Mental Health, National Institutes of Health, US Department of Health and Human Services, Bethesda, MD, United States
pq Molecular and Behavioral Neuroscience Institute, University of Michigan, Ann Arbor, MI, United States
pr Department of Psychiatry, University of Michigan, Ann Arbor, MI, United States
ps SRH University Heidelberg, Academy for Psychotherapy, Heidelberg, Germany
pt Division of Neuroscience, School of Medicine, University of Dundee, Dundee, United Kingdom
pu Advanced Interventions Service, NHS Tayside, Dundee, United Kingdom
pv NORMENT, K.G. Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway
pw Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway
px Cognitive Genetics and Cognitive Therapy Group, Neuroimaging, Cognition and Genomics (NICOG) Centre, School of Psychology and Discipline of Biochemistry, National University of Ireland Galway, Galway, Ireland
py Division of Psychiatry, University of Edinburgh, Edinburgh, United Kingdom
pz Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden
qa Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden
qb Neuroscience Research Australia, Sydney, Australia
qc School of Medical Sciences, University of New South Wales, Sydney, Australia
qd Unidad de Salud Mental, Hospital Regional Universitario de Malaga, Malaga, Spain
qe Instituto de Investigación Biomédica de Málaga (IBIMA), Malaga, Spain
qf Department of Biomedicine, University of Basel, Basel, Switzerland
qg Institute of Neuroscience and Medicine (INM-1), Research Centre Jülich, Jülich, Germany
qh Institute of Human Genetics, University of Bonn, Bonn, Germany
qi Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
qj School of Psychiatry, University of New South Wales, Sydney, Australia
qk Black Dog Institute, Sydney, Australia
ql University of Chicago, Chicago, IL, United States
qm Washington University, St. Louis, MO, United States
qn Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States
qo Department of Psychiatry, Dalhousie University, Halifax, Canada
qp National Institute of Mental Health, Klecany, Czech Republic
qq Montreal Neurological Institute, McGill University, Montréal, Canada
qr Department of Neurology and Neurosurgery, McGill University, Montréal, Canada
qs Department of Psychiatry, McGill University, Montréal, Canada
qt University College London, London, United Kingdom
qu Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, University of California at Los Angeles, Los Angeles, CA, United States
qv UMC Utrecht, Utrecht, Netherlands
qw SUNY Downstate Medical Center, Brooklyn, NY, United States
qx Hospital for Psychiatry and Psychotherapy, Cologne, Germany
qy Laboratory of Psychiatric Genetics, Department of Psychiatry, Poznan University of Medical Sciences, Poznan, Poland
qz Douglas Mental Health University Institute, McGill University, Montreal, Canada
ra Department of Translational Research in Psychiatry, Max-Planck Institute of Psychiatry, Munich, Germany
rb National Centre for Mental Health, MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, United Kingdom
rc Department Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, VU University, Amsterdam, Netherlands
rd Department Clinical Genetics, VU University Medical Center, Amsterdam Neuroscience, Amsterdam, Netherlands
re Department of Neurology, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany
rf Department of Psychiatry (UPK), University of Basel, Basel, Switzerland
rg Discipline of Psychiatry, University of Adelaide, Adelaide, Australia
rh Queensland Brain Institute, University of Queensland, Brisbane, Australia
ri Bela Menso Brain and Behaviour Centre, James Cook University, Varsity Lakes, Australia
rj Bond University, Faculty of Society and Design, Robina, Australia
rk Division of Psychiatry, Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, United Kingdom
rl Centre for Genomic and Experimental Medicine, University of Edinburgh, Edinburgh, United Kingdom
rm Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald, Germany
rn Department of Biochemistry and Molecular Biology II, Institute of Neurosciences, Center for Biomedical Research, University of Granada, Granada, Spain
ro Bioinformatics Research Centre, Aarhus University, Aarhus, Denmark
rp Child Health Research Centre, University of Queensland, Brisbane, Australia
rq Child and Youth Mental Health Service, Children’s HealthQueensland Health and Hospital Service, Brisbane, Australia
rr Brain and Mind Centre, University of Sydney, Sydney, Australia
rs School of Psychology and Counselling, Faculty of Health, Institute of Health and Biomedical Innovation, Queensland University of TechnologyQLD, Australia
rt University of Queensland, Brisbane, Australia
ru Department of Psychiatry, Harvard Medical School, Boston, MA, United States
rv Amsterdam Public Health Research Institute, VU Medical Center, Amsterdam, Netherlands
rw Department of Research and Innovation, GGZ Ingeest, Specialized Mental Health Care, Amsterdam, Netherlands
rx Janssen Research and Development LLC, Titusville, NJ, United States
ry Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany
rz German Centre for Cardiovascular Research (DZHK e.V.), Partner Site Greifswald, Greifswald, Germany
sa Research School of Behavioural and Cognitive Neurosciences, Department of Psychiatry, University Medical Center Groningen, University of Groningen, Groningen, Netherlands
sb Department of Psychiatry GGZ INGEEST, Amsterdam, Netherlands
sc Department of Cell Biology, SUNY Downstate Medical Center, Brooklyn, NY, United States
sd Mathison Centre for Mental Health Research and Education, Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, Canada
se Departments of Psychiatry and Medical Genetics, Cumming School of Medicine, University of Calgary, Calgary, Canada
sf Krembil Research Institute, University Health Network, Toronto, Canada
sg Grupo de Genética Molecular, Instituto de Biología, Facultad de Ciencias Exactas y Naturales, Universidad de Antioquia, Medellín, Colombia
sh Johns Hopkins University, School of Medicine, Baltimore, MD, United States
si Department of Psychiatry, Sao Paulo Medical School, University of Sao Paulo, Sao Paulo, Brazil
sj Depto. Farmacogenética, Instituto Nacional de Psiquiatria Ramon de la Fuente Muñiz, Mexico City, Mexico
sk University of Groningen, Groningen, Netherlands
sl Department of Psychiatry, University of Groningen, University Medical Center, Groningen, Netherlands
sm Department of Specialized Trainings, GGZ Drenthe Mental Health Care Services, Assen, Netherlands
sn Ospedale San Raffaele, Milano, Italy
so Bio4Dreams Srl, Milan, Italy
sp University of California, San Francisco, CA, United States
sq Yale University, School of Medicine, New Haven, CT, United States
sr Department of Psychiatry, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands
ss Netherlands Institute for Neuroscience, Royal Netherlands Academy of Arts and Sciences, Amsterdam, Netherlands
st Department of Child and Adolescent Psychiatry, University Medical Center Groningen, University of Groningen, Groningen, Netherlands
su Centre National Maladie ‘Syndrome Rare Gilles de la Tourette’, Groupe Hospitalier Pitié-Salpêtrière, Paris, France
sv Assistance Publique-Hôpitaux de Paris, Départment de Neurologie, Groupe Hospitalier Pitié-Salpêtrière, Paris, France
sw Sorbonne Universités, UPMC Université Paris 06, UMR S 1127, CNRS UMR 7225, ICM, Paris, France
sx Bioinformatics Interdepartmental Program, University of California, Los Angeles, Los Angeles, CA, United States
sy De Bascule, Amsterdam, Netherlands
sz Department of Child and Adolescent Psychiatry, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands
ta Carver College of Medicine, University of Iowa, Iowa City, IA, United States
tb MRC Unit on Risk and Resilience in Mental Disorders, Department of Psychiatry, University of Cape Town, Cape Town, South Africa
tc Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, United States
td Department of Psychiatry and Human Behavior, University of California, Irvine, Irvine, CA, United States
te Department of Neurology, University of Florida, Gainesville, FL, United States
tf Sección de Neuropediatría, Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío, CSIC, Universidad de Sevilla, Seville, Spain
tg Yulius Academy, Yulius Mental Health Organization, Barendrecht, Netherlands
th Department of Psychology, University of Denver, Denver, CO, United States
ti Faculdade de Medicina FMUSP, Universidade de São Paulo, São Paulo, Brazil
tj Unidad de Trastornos del Movimiento, Servicio de Neurología y Neurofisiología Clínica, Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío, CSIC, Universidad de Sevilla, Seville, Spain
tk Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain
tl National Institute of Genomic Medicine (INMEGEN), Ciudad de México, Mexico
tm Clinical Research, Grupo Médico Carracci, Mexico City, Mexico
tn Departments of Neurology and Neurosurgery, University of Florida, Gainesville, FL, United States
to Fixel Center for Neurological Diseases, University of Florida, Gainesville, FL, United States
tp McKnight Brain Institute, University of Florida, Gainesville, FL, United States
tq Department of Psychiatry, Yale School of Medicine, New Haven, CT, United States
tr Department of Biological Sciences, Purdue University, West Lafayette, IN, United States
ts Division of Adolescent and Child Psychiatry, Department of Psychiatry, Lausanne University Hospital, Lausanne, Switzerland
tt Child and Adolescent Mental Health Centre, Mental Health Services Capital Region Copenhagen, University of Copenhagen, Copenhagen, Denmark
tu Moscow Institute of Physics and Technology, Dolgoprudny, Institusky 9, Moscow, Russian Federation
tv Department of Psychiatry, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, United States
tw Frederick W. Thompson Anxiety Disorders Centre, Sunnybrook Health Sciences Centre, Toronto, Canada
tx Department of Psychiatry, University of Toronto, Toronto, Canada
ty Division of Neuropsychiatry, University College London, London, United Kingdom
tz Department of Child and Adolescent Psychiatry, Faculty of Medicine, Technischen Universität Dresden, Dresden, Germany
ua Child and Adolescent Psychiatry Unit (UPIA), Department of Psychiatry, Federal University of São Paulo, Brazil
ub Yale Child Study Center, Yale University, School of Medicine, New Haven, CT, United States
uc University Health Network, University of Toronto, Toronto, Canada
ud Youthdale Treatment Centers, Toronto, Canada
ue Groote Schuur Hospital, Cape Town, South Africa
uf Department of Molecular Biology and Genetics, Democritus University of Thrace, Alexandroupolis, Greece
ug Laboratory of Pharmaceutical Biotechnology, Ghent University, Ghent, Belgium
uh Pfizer, Inc., New York, NY, United States
ui Department of Child Psychiatry, Medical University of Warsaw, Warsaw, Poland
uj Sorbonne Université, Faculty of Médecine, Paris, France
uk Reference center for Gilles de la Tourette syndrome, Pitie-Salpetriere Hospital, Paris, France
ul Department of Physiology, Saint Antoine Hospital, Paris, France
um Butler Hospital, Providence, RI, United States
un Alpert Medical School, Brown University, Providence, RI, United States
uo Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany
up Institute of Human Genetics, University Hospital Essen, University Duisburg-Essen, Essen, Germany
uq INSERM, U 1127, CNRS UMR 7225, Sorbonne Universités, UPMC Univ Paris 06 UMR S 1127, Paris, France
ur IGBMC, CNRS UMR 7104, INSERM U964, Université de Strasbourg, Illkirch, France
us Vanderbilt University Medical Center, Nashville, TN, United States
ut Escuela de Ciencias de la Salud, Universidad Pontificia Bolivariana, Medellín, Colombia
uu Laboratorio de Genética Molecular, SIU, Universidad de Antioquia, Medellín, Colombia
uv School of Nursing, Louisiana State University Health Sciences Center, New Orleans, LA, United States
uw Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, Netherlands
ux School of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, Australia
uy Priority Research Centre for Brain and Mental Health Research, Hunter Medical Research Institute, Newcastle, Australia
uz Schizophrenia Research Institute, Sydney, Australia
va Institute of Mental Health, Singapore, Singapore
vb Assistance Publique – Hopitaux de Paris, GH Pitié-Salpêtrière, Paris, France
vc Sorbonne Université, CNRS UMR 7222 Institut des Systèmes Intelligents et Robotiques, Paris, France
vd Departments of Medicine and Psychiatry, School of Medicine, University of Cantabria-IDIVAL, University Hospital Marqués de Valdecilla, Santander, Spain
ve Minerva Neurosciences Inc., Waltham, MA, United States
vf Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
vg VA Boston Healthcare System, Boston, MA, United States
vh APC Microbiome Ireland, University College Cork, Cork, Ireland
vi Department of Psychiatry, University College Cork, Cork, Ireland
vj Neuroimaging, Cognition and Genomics (NICOG) Centre, School of Psychology, National University of Ireland Galway, Galway, Ireland
vk Center for Psychiatric Genetics, NorthShore University HealthSystem Research Institute, Evanston, IL, United States
vl Department of Psychiatry and Behavioral Neuroscience, University of Chicago, Chicago, IL, United States
vm Arkin, Amsterdam, Netherlands
vn Department for Congenital Disorders, Statens Serum Institut, Copenhagen, Denmark
vo Department of Medical Genetics, Medical University, Sofia, Bulgaria
vp Department of Molecular Bases of Human Genetics, Institute of Molecular Genetics, Russian Academy of Sciences, Moscow, Russian Federation
vq Latvian Biomedical Research and Study Centre, Riga, Latvia
vr Vilnius University, Vilnius, Lithuania
vs Institute of Mental Health, Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore
vt Department of Human Genetics, Institute of Molecular Genetics, Russian Academy of Sciences, Moscow, Russian Federation
vu Hunter New England Local Health District, Newcastle, Australia
vv Department of Psychiatry, University of Helsinki, Helsinki, Finland
vw Department of Psychiatry, Psychosomatics and Psychotherapy, Center of Mental Health, University Hospital Wuerzburg, Wuerzburg, Germany
vx Department of Biomedicine, Aarhus University, Aarhus, Denmark
vy Department of Clinical Neuroscience, Centre for Psychiatry Research, Karolinska Institutet, Stockholm, Sweden
vz Centre for Neuroimaging and Cognitive Genomics (NICOG), National University of Ireland, Galway, Galway, Ireland
wa NCBES Galway Neuroscience Centre, National University of Ireland, Galway, Galway, Ireland
wb Department of Psychiatry, Royal College of Surgeons in Ireland, Dublin, Ireland
wc Philipps-Universität Marburg, Marburg University Hospital UKGM, Marburg, Germany
wd Department of Psychiatry and Psychotherapy, Jena University Hospital, Jena, Germany
we Maastricht University Medical Centre, Maastricht, Netherlands
wf Department of Psychosis Studies, Institute of Psychiatry, King’s College London, London, United Kingdom
wg Melbourne Neuropsychiatry Centre, Department of Psychiatry, University of Melbourne, Melbourne HealthVIC, Australia
wh Centre for Neural Engineering, Department of Electrical and Electronic Engineering, University of Melbourne, Victoria, Australia
wi Oxford Health NHS Foundation Trust, Oxford, United Kingdom
wj Department of Psychiatry, University of Oxford, Oxford, United Kingdom
wk Department of Psychiatry and Behavioral Sciences, NorthShore University HealthSystem Research Institute, Evanston, IL, United States
wl Faculty of Science, Medicine and Health, University of Wollongong, Wollongong, Australia
wm Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
wn Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore
wo School of Biomedical Sciences, Chinese University of Hong Kong, Shatin, Hong Kong
wp KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research of Common Diseases, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China
wq Chinese University of Hong Kong, Hong Kong
wr Sheba Medical Center, Ramat Gan, Israel
ws Departments of Psychiatry and Genetics, Washington University, School of Medicine, St. Louis, MO, United States
wt UCL Genetics Institute, University College London, London, United Kingdom
wu Centre for Psychiatry, Barts and the London School of Medicine and Dentistry, London, United Kingdom
wv School of Medicine and Public Health, University of Newcastle, Callaghan, Australia
ww Priority Research Centre for Health Behaviour, University of Newcastle, Callaghan, Australia
wx Research Unit, Sørlandet Hospital, Kristiansand, Norway
wy Department of Statistics and Applied Probability, University of California, Santa Barbara, CA, United States
wz Computational Research Division, Lawrence Berkeley National Laboratory, University of California at Berkeley, Berkeley, CA, United States
xa NSW Health Pathology, Newcastle, Australia
xb Virginia Institute for Psychiatric and Behavioral Genetics, Department of Psychiatry, Virginia Commonwealth University, Richmond, VA, United States
xc Institute of Psychiatry, Psychology and Neuroscience, Social Genetics and Developmental Psychiatry Center, MRC, Kings College London, London, United Kingdom
xd NIHR Maudsley Biomedical Research Centre, South London and Maudsley NHS Trust and King’s College London, London, United Kingdom
xe Departments of Psychiatry and Nutrition, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States
xf Departments of Psychiatry and of Neuroscience and Physiology, SUNY Upstate Medical University, Syracuse, NY, United States
xg Department of Psychiatry, Virginia Commonwealth University, Richmond, VA, United States
xh Division Biomedical Genetics, University Medical Center Utrecht, Utrecht, Netherlands
xi Department of Psychiatry and UF Genetics Institute, University of Florida, Gainesville, FL, United States
xj Division of Cognitive and Behavioral Neurology, Brigham and Women’s Hospital, Boston, MA, United States
xk Department of Neurology, Yale School of Medicine, New Haven, CT, United States
xl Department of Genetics and Psychiatry, University of North Carolina, School of Medicine, Chapel Hill, NC, United States
xm Neuropsychiatric Genetics Research Group, Department of Psychiatry, Trinity Colle e Dublin, Dublin, Ireland

Abstract
Disorders of the brain can exhibit considerable epidemiological comorbidity and often share symptoms, provoking debate about their etiologic overlap. We quantified the genetic sharing of 25 brain disorders from genome-wide association studies of 265,218 patients and 784,643 control participants and assessed their relationship to 17 phenotypes from 1,191,588 individuals. Psychiatric disorders share common variant risk, whereas neurological disorders appear more distinct from one another and from the psychiatric disorders. We also identified significant sharing between disorders and a number of brain phenotypes, including cognitive measures. Further, we conducted simulations to explore how statistical power, diagnostic misclassification, and phenotypic heterogeneity affect genetic correlations. These results highlight the importance of common genetic variation as a risk factor for brain disorders and the value of heritability-based methods in understanding their etiology. © 2018 American Association for the Advancement of Science. All rights reserved.

Document Type: Article
Source: Scopus

"Scaling of human brain size" (2018) Science (New York, N.Y.)

Scaling of human brain size
(2018) Science (New York, N.Y.), 360 (6394), pp. 1184-1185. 

Van Essen, D.C.

Washington University, St. Louis, MO, USA. vanessen@wustl.edu

Document Type: Note
Source: Scopus

"B cells are capable of independently eliciting rapid reactivation of encephalitogenic CD4 T cells in a murine model of multiple sclerosis" (2018) PLoS ONE

B cells are capable of independently eliciting rapid reactivation of encephalitogenic CD4 T cells in a murine model of multiple sclerosis
(2018) PLoS ONE, 13 (6), art. no. e0199694, . 

Parker Harp, C.R.a , Archambault, A.S.a , Sim, J.b , Shlomchik, M.J.c , Russell, J.H.b , Wu, G.F.a d

a Department of Neurology, Washington University School of Medicine, St. Louis, MO, United States
b Department of Developmental Biology, Washington University School of Medicine, St. Louis, MO, United States
c Department of Immunology, University of Pittsburgh, Pittsburgh, PA, United States
d Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, United States

Abstract
Recent success with B cell depletion therapies has revitalized efforts to understand the pathogenic role of B cells in Multiple Sclerosis (MS). Using the adoptive transfer system of experimental autoimmune encephalomyelitis (EAE), a murine model of MS, we have previously shown that mice in which B cells are the only MHCII-expressing antigen presenting cell (APC) are susceptible to EAE. However, a reproducible delay in the day of onset of disease driven by exclusive B cell antigen presentation suggests that B cells require optimal conditions to function as APCs in EAE. In this study, we utilize an in vivo genetic system to conditionally and temporally regulate expression of MHCII to test the hypothesis that B cell APCs mediate attenuated and delayed neuroinflammatory T cell responses during EAE. Remarkably, induction of MHCII on B cells following the transfer of encephalitogenic CD4 T cells induced a rapid and robust form of EAE, while no change in the time to disease onset occurred for recipient mice in which MHCII is induced on a normal complement of APC subsets. Changes in CD4 T cell activation over time did not account for more rapid onset of EAE symptoms in this new B cell-mediated EAE model. Our system represents a novel model to study how the timing of pathogenic cognate interactions between lymphocytes facilitates the development of autoimmune attacks within the CNS. © This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

Document Type: Article
Source: Scopus
Access Type: Open Access

"Clemastine effects in rat models of a myelination disorder" (2018) Pediatric Research

, 83 (6), pp. 1200-1206. 

Turski, C.A.a , Turski, G.N.b , Chen, B.c , Wang, H.d , Heidari, M.e , Li, L.c , Noguchi, K.K.d , Westmark, C.a , Duncan, I.e , Ikonomidou, C.a

a Department of Neurology, University of Wisconsin, Madison, WI, United States
b Department of Ophthalmology, Rheinische Friedrich Wilhelms University, Bonn, Germany
c School of Pharmacy and Department of Chemistry, University of Wisconsin, Madison, WI, United States
d Department of Psychiatry, Washington University, St Louis, MO, United States
e Department of Medical Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI, United States

Abstract
BackgroundPelizaeus Merzbacher disease (PMD) is a dysmyelinating disorder of the central nervous system caused by impaired differentiation of oligodendrocytes. This study was prompted by findings that antimuscarinic compounds enhance oligodendrocyte differentiation and remyelination in vitro. One of these compounds, clemastine fumarate, is licensed for treatment of allergic conditions. We tested whether clemastine fumarate can promote myelination in two rodent PMD models, the myelin-deficient and the PLP transgenic rat.MethodsPups were treated with daily injections of clemastine (10-30 mg/kg/day) on postnatal days 1-21. Neurologic phenotypes and myelination patterns in the brain, optic nerves, and spinal cords were assessed using histological techniques.ResultsNo changes in neurological phenotype or survival were observed even at the highest dose of clemastine. Postmortem staining with Luxol fast blue and myelin basic protein immunohistochemistry revealed no evidence for improved myelination in the CNS of treated rats compared to vehicle-treated littermates. Populations of mature oligodendrocytes were unaffected by the treatment.ConclusionThese results demonstrate lack of therapeutic effect of clemastine in two rat PMD models. Both models have rapid disease progression consistent with the connatal form of the disease. Further studies are necessary to determine whether clemastine bears a therapeutic potential in milder forms of PMD. © 2018 International Pediatric Research Foundation, Inc.

Document Type: Article
Source: Scopus

"Formal idiographic inference in medicine" (2018) JAMA Otolaryngology – Head and Neck Surgery

Formal idiographic inference in medicine
(2018) JAMA Otolaryngology – Head and Neck Surgery, 144 (6), pp. 467-468. 

Barbour, D.L.

Departments of Biomedical Engineering, Neuroscience and Otolaryngology, Washington University in St Louis, 1 Brookings Dr, Campus Box 1097, St. Louis, MO, United States

Document Type: Note
Source: Scopus

"Executive function predicts antidepressant treatment noncompletion in late-life depression" (2018) Journal of Clinical Psychiatry

Executive function predicts antidepressant treatment noncompletion in late-life depression
(2018) Journal of Clinical Psychiatry, 79 (3), art. no. 16m11371, . 

Cristancho, P.a , Lenze, E.J.a , Dixon, D.a , Miller, J.P.b , Mulsant, B.H.c , Reynolds, C.F., IIId , Butters, M.A.d

a Department of Psychiatry, Healthy Mind Laboratory, School of Medicine, Washington University in St Louis, 660 S. Euclid Ave, St Louis, MO, United States
b Division of Biostatistics, School of Medicine, Washington University in St Louis, St Louis, MO, United States
c Centre for Addiction and Mental Health, Department of Psychiatry, University of Toronto, Toronto, ON, Canada
d Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, United States

Abstract
Objective: To examine whether executive function (EF) is associated with nonremission and noncompletion of antidepressant pharmacotherapy in older adults with depression. Design: In this prospective study (July 2009 to May 2014), older adults (aged ≥ 60 years; n = 468) with a DSM-IV-defined major depressive episode diagnosed via structured interview received 12 weeks of venlafaxine extended release with the goal of achieving remission. A hypothesis was made that worse baseline EF would predict both nonremission and noncompletion (primary outcomes). Treatment-related factors, including side effects and nonadherence, were also studied. Methods: Baseline EF, including response inhibition and set-shifting, was assessed with subtests of the Delis-Kaplan Executive Function System and the semantic fluency subtest of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Attention, immediate memory, delayed memory, visuospatial ability, and global cognition were also assessed with the RBANS. Results: Of 468 participants, 96 (21%) failed to complete the treatment trial, 191 (41%) completed and remitted, and 181 (39%) completed and did not remit. Univariate analyses indicated that some EFs (setshifting and semantic fluency) and other cognitive variables (attention, immediate memory, visuospatial ability, and global cognition) predicted treatment noncompletion, whereas no cognitive variables predicted nonremission. In a multivariate logistic regression model, semantic fluency (P = .003), comorbid medical burden (P < .001), and early nonadherence (P < .001) were significant predictors of treatment noncompletion. Conclusions: Poorer EF predicted treatment noncompletion. These findings suggest that EFs of initiation and set maintenance (examined by the semantic fluency task) may allow depressed elderly individuals to engage and stay in treatment. Identification of those at risk for noncompletion may help implementation strategies for personalized care. © Copyright 2018 Physicians Postgraduate Press, Inc.

Document Type: Article
Source: Scopus

"Important Details in Performing and Interpreting the Scratch Collapse Test" (2018) Plastic and reconstructive surgery

Important Details in Performing and Interpreting the Scratch Collapse Test
(2018) Plastic and reconstructive surgery, 141 (2), pp. 399-407. 

Kahn, L.C., Yee, A., Mackinnon, S.E.

Saint Louis, Mo. From the Division of Plastic and Reconstructive Surgery, Department of Surgery, and the Department of Occupational Therapy, Milliken Hand Rehabilitation Center, Washington University School of Medicine

Abstract
The utility of the scratch collapse test has been demonstrated in examination of patients with carpal and cubital tunnel syndromes and long thoracic and peroneal nerve compressions. In the authors’ clinic, this lesser known test plays a key role in peripheral nerve examination where localization of the nerve irritation or injury is not fully understood. Test utility and accuracy in patients with more challenging presentations likely correlate with tester understanding and experience. This article offers a clear outline of all stages of the test to improve interrater reliability. The nuances of test performance are described, including a description of situations where the scratch collapse test is deemed inappropriate. Four clinical scenarios where the scratch collapse test may be useful are included. Corresponding video content is provided to improve performance and interpretation of the scratch collapse test.

CLINICAL QUESTION/LEVEL OF EVIDENCE: Diagnostic, V.

Document Type: Article
Source: Scopus

"Preoperative Variables Associated With Respiratory Complications After Pediatric Neuromuscular Spine Deformity Surgery" (2018) Spine Deformity

Preoperative Variables Associated With Respiratory Complications After Pediatric Neuromuscular Spine Deformity Surgery
(2018) Spine Deformity, . Article in Press. 

Luhmann, S.J., Furdock, R.

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

Abstract
Objective: The objective of this study is to identify preoperative laboratory values and patient factors that are associated with postoperative respiratory complications in pediatric neuromuscular scoliosis (NMS) populations undergoing posterior spinal fusion (PSF) with instrumentation. Summary of Background Data: PSF in NMS patients are high-risk surgeries. Respiratory complications are the most common postoperative event, with rates up to 28.2% following surgery. Methods: A single-surgeon, two-hospital pediatric spine surgery database was reviewed to identify all patients who underwent PSF for NMS. Diagnoses included cerebral palsy (n=83), myelomeningocele (n=13), spinal muscular atrophy (n=4), and other (n=11). This study defined respiratory complications as postoperative pneumonia, pleural effusion, pneumothorax, need for reintubation, respiratory status requiring a return to the pediatric intensive care unit (PICU), or prolonged (>4-day) need for mechanical ventilation. Preoperative laboratory values for transferrin, prealbumin, hemoglobin/hematocrit, total protein, albumin, and total lymphocyte count were collected. Results: There were 50 males and 61 females with a mean age of 14 years 2.5 months (8–20 years). Seventeen patients (15.3%) experienced postoperative respiratory complications. On univariate analysis, any history of pneumonia, the presence of gastrostomy tube, and low transferrin levels were associated with postoperative respiratory complications, and a strong trend (p=.06) was observed for tracheostomy. On multivariate analysis, the presence of gastrostomy tube and history of pneumonia remained as clinically significant predictors of postoperative respiratory complications. Conclusion: Pediatric NMS patients undergoing PSF that have history of pneumonia or gastrostomy tube present at time of surgery are at increased risk for postoperative respiratory complications. The univariate associations of tracheostomy presence and low transferrin levels with postoperative respiratory complications deserve further examination. Level of Evidence: Level II. © 2018 Scoliosis Research Society

Author Keywords
Neuromuscular;  Respiratory complications;  Spinal fusion;  Spine deformity

Document Type: Article in Press
Source: Scopus

"Radiologic Response and Disease Control of Recurrent Intracranial Meningiomas Treated With Reirradiation" (2018) International Journal of Radiation Oncology Biology Physics

Radiologic Response and Disease Control of Recurrent Intracranial Meningiomas Treated With Reirradiation
(2018) International Journal of Radiation Oncology Biology Physics, . Article in Press.

Lin, A.J.a , Hui, C.a , Dahiya, S.b , Lu, H.-C.b , Kim, A.H.c , Campian, J.L.d , Tsien, C.a , Zipfel, G.J.c , Rich, K.M.c , Chicoine, M.c , Huang, J.a  

a Department of Radiation Oncology, Division of Oncology, Washington University School of Medicine, St Louis, Missouri, United States
b Department of Pathology and Immunology, Division of Oncology, Washington University School of Medicine, St Louis, Missouri, United States
c Department of Neurosurgery, Division of Oncology, Washington University School of Medicine, St Louis, Missouri, United States
d Department of Medicine, Washington University School of Medicine, St Louis, Missouri, United States

Abstract
Purpose: To evaluate the clinical outcomes of reirradiation of recurrent meningiomas and factors related to patient selection and treatment modality. Methods and Materials: Recurrent meningioma patients who failed prior stereotactic radiosurgery (SRS) or fractionated external beam radiation therapy (EBRT) received reirradiation using either SRS or EBRT. Complete response (CR), partial response (PR), and progression after reirradiation were evaluated using the MacDonald criteria. Local control (LC), progression-free survival (PFS), and overall survival (OS) after reirradiation were analyzed using the Kaplan-Meier method. Logistic and Cox regression analyses were performed to identify factors associated with reirradiation modality and PFS, respectively. Results: Forty-three patients (14 grade 1/unknown, 29 grade 2/3) were reirradiated with SRS (67%) or EBRT (33%). Median time from initial SRS/EBRT to reirradiation was 60 months (range, 7.5-202); median tumor volume at the time of reirradiation was 4.8 cm3 (range, 0.14-64). After a median radiologic follow-up of 19.4 months, the response rate (CR + PR) was 8% for grade 1 and 20% for grade 2/3 meningiomas. After 2 years, LC was 78%, PFS was 63%, and OS was 80%. Larger tumor volume and prior SRS were associated with reirradiation using EBRT. Reirradiated grade 2/3 meningiomas had significantly worse PFS than grade 1 (2-year PFS: 50% vs 92%, respectively; P = .02) but not LC (P = .11) or OS (P = .39). On multivariable analysis, worse PFS was significantly associated with grade 2/3 histology (hazard ratio, 3.92; 95% confidence interval, 1.33-11.6) as well as worse Karnofsky Performance Scale score but not reirradiation dose, volume, and modality. Grades 3 to 4 radiation necrosis developed in 4 patients (10%). Conclusions: Reirradiation of recurrent meningiomas appears to be feasible with promising clinical outcomes and an acceptable toxicity profile. © 2018 Elsevier Inc.

Document Type: Article in Press
Source: Scopus

"Neurostimulation for depression in epilepsy" (2018) Epilepsy and Behavior

Neurostimulation for depression in epilepsy
(2018) Epilepsy and Behavior, . Article in Press. 

Conway, C.R.a , Udaiyar, A.b , Schachter, S.C.c

a Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8134, Saint Louis, MO, United States
b 4400 Lindell Boulevard, Apt 7 A, Saint Louis, MO, United States
c Beth Israel Deaconess Medical Center, Massachusetts General Hospital, CIMIT- 125 Nashua Street, Suite 324, Boston, MA, United States

Abstract
Epilepsy is often associated with comorbid psychiatric illnesses that can significantly impact its long-term course. The most frequent of these psychiatric comorbidities is major depressive disorder, which affects an estimated 40% of patients with epilepsy. Many patients are underdiagnosed or undertreated, yet managing their mood symptoms is critical to improving their outcomes. When conventional psychiatric treatments fail in the management of depression, neuromodulation techniques may offer promise, including electroconvulsive therapy (ECT), vagus nerve stimulation (VNS), and repetitive transcranial magnetic stimulation (rTMS), as discussed in this review. This article is part of the Special Issue “Neurostimulation for Epilepsy”. © 2018

Author Keywords
Electroconvulsive therapy;  Epilepsy;  Major depression;  Neuromodulation;  Repetitive transcranial magnetic stimulation;  Vagus nerve stimulation

Document Type: Article in Press
Source: Scopus

"Inspired by the past and looking to the future of the Stroop effect" (2018) Acta Psychologica

Inspired by the past and looking to the future of the Stroop effect
(2018) Acta Psychologica, . Article in Press. 

Henik, A.a , Bugg, J.M.b , Goldfarb, L.c

a Ben-Gurion University of the Negev, Israel
b Washington University in St. Louis, United States
c University of Haifa, Israel

Document Type: Article in Press
Source: Scopus

"De Novo Mutation in Genes Regulating Neural Stem Cell Fate in Human Congenital Hydrocephalus" (2018) Neuron

De Novo Mutation in Genes Regulating Neural Stem Cell Fate in Human Congenital Hydrocephalus
(2018) Neuron, . Article in Press. 

Furey, C.G.a b , Choi, J.a , Jin, S.C.a , Zeng, X.a , Timberlake, A.T.a , Nelson-Williams, C.a , Mansuri, M.S.b , Lu, Q.c , Duran, D.b , Panchagnula, S.b , Allocco, A.b , Karimy, J.K.b , Khanna, A.d , Gaillard, J.R.b , DeSpenza, T.b , Antwi, P.b , Loring, E.a , Butler, W.E.d , Smith, E.R.e , Warf, B.C.e , Strahle, J.M.f , Limbrick, D.D.f , Storm, P.B.g h , Heuer, G.g h , Jackson, E.M.i , Iskandar, B.J.j , Johnston, J.M.k , Tikhonova, I.l , Castaldi, C.l , López-Giráldez, F.l , Bjornson, R.D.l , Knight, J.R.a l , Bilguvar, K.l , Mane, S.l , Alper, S.L.m , Haider, S.n , Guclu, B.o , Bayri, Y.p , Sahin, Y.p , Apuzzo, M.L.J.b , Duncan, C.C.b , DiLuna, M.L.b , Günel, M.a b , Lifton, R.P.a q , Kahle, K.T.a b r

a Department of Genetics, Yale University School of Medicine, New Haven, CT, United States
b Department of Neurosurgery, Yale University School of Medicine, New Haven, CT, United States
c Department of Biostatistics & Medical Informatics, University of Wisconsin, Madison, WI, United States
d Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States
e Department of Neurosurgery, Boston Children’s Hospital, Harvard Medical School, Boston, MA, United States
f Department of Neurological Surgery and Pediatrics, Washington University in St. Louis School of Medicine, St. Louis, MO, United States
g Department of Neurosurgery, Hospital of the University of Pennsylvania, Philadelphia, PA, United States
h Division of Neurosurgery, Children’s Hospital of Philadelphia, Philadelphia, PA, United States
i Department of Neurosurgery, Johns Hopkins School of Medicine, Baltimore, MD, United States
j Department of Neurological Surgery, University of Wisconsin Medical School, Madison, WI, United States
k Department of Neurosurgery, University of Alabama School of Medicine, Birmingham, AL, United States
l Yale Center for Genome Analysis, Yale University, New Haven, CT, United States
m Division of Nephrology and Center for Vascular Biology Research, Beth Israel Deaconess Medical Center, Department of Medicine, Harvard Medical School, Boston, MA, United States
n Department of Pharmaceutical and Biological Chemistry, University College London School of Pharmacy, London, United Kingdom
o Kartal Dr. Lutfi Kirdar Research and Training Hospital, Istanbul, Turkey
p Acibadem Mehmet Ali Aydinlar University, School of Medicine, Department of Neurosurgery, Division of Pediatric Neurosurgery, Istanbul, Turkey
q Laboratory of Human Genetics and Genomics, The Rockefeller University, New York, NY, United States
r Department of Cellular & Molecular Physiology, Yale University School of Medicine, New Haven, CT, United States

Abstract
Congenital hydrocephalus (CH), featuring markedly enlarged brain ventricles, is thought to arise from failed cerebrospinal fluid (CSF) homeostasis and is treated with lifelong surgical CSF shunting with substantial morbidity. CH pathogenesis is poorly understood. Exome sequencing of 125 CH trios and 52 additional probands identified three genes with significant burden of rare damaging de novo or transmitted mutations: TRIM71 (p = 2.15 × 10−7), SMARCC1 (p = 8.15 × 10−10), and PTCH1 (p = 1.06 × 10−6). Additionally, two de novo duplications were identified at the SHH locus, encoding the PTCH1 ligand (p = 1.2 × 10−4). Together, these probands account for 10% of studied cases. Strikingly, all four genes are required for neural tube development and regulate ventricular zone neural stem cell fate. These results implicate impaired neurogenesis (rather than active CSF accumulation) in the pathogenesis of a subset of CH patients, with potential diagnostic, prognostic, and therapeutic ramifications. © 2018 Elsevier Inc.

Congenital hydrocephalus (CH) is a major cause of childhood morbidity and mortality, affecting 1 in 1,000 live births and representing up to 3% of all pediatric hospital charges. Using data from the largest CH exome sequencing study to date, Furey et al. identify four genes (TRIM71, SMARCC1, PTCH1, and SHH) not previously implicated in CH. Remarkably, all four genes regulate ventricular zone neural stem cell fate and, together, explain 10% of CH cases. These findings implicate impaired neurogenesis in pathogenesis of a significant number of CH patients, with potential diagnostic, prognostic, and therapeutic ramifications.

Author Keywords
aqueductal stenosis;  congenital hydrocephalus;  de novo variants;  gene discovery;  neural stem cell;  PTCH1;  SHH;  SMARCC1;  TRIM71;  whole-exome sequencing

Document Type: Article in Press
Source: Scopus

"A case of oligodendroglioma and multiple sclerosis: Occam's razor or Hickam's dictum?" (2018) BMJ Case Reports

A case of oligodendroglioma and multiple sclerosis: Occam’s razor or Hickam’s dictum?
(2018) BMJ Case Reports, 2018, art. no. bcr-2018-225318, . 

Shirani, A.a , Wu, G.F.a , Giannini, C.b , Cross, A.H.a

a Department of Neurology, Washington University, Saint Louis School of Medicine, St Louis, MO, United States
b Department of Laboratory Medicine and Pathology, Mayo Clinic College of Medicine, Rochester, United States

Abstract
Tumefactive appearing lesions on brain imaging can cause a diagnostic dilemma. We report a middle-aged man who presented with right-sided optic neuritis. A brain MRI showed enhancement of the right optic nerve, and non-enhancing white matter lesions including a 3 cm right frontal lesion with adjacent gyral expansion. Cerebrospinal fluid analysis showed five oligoclonal bands not present in serum. Glatiramer acetate was started for suspected tumefactive multiple sclerosis (MS). A follow-up brain MRI 6 months later showed persistence of the frontal gyral expansion. A brain biopsy led to the diagnosis of an oligodendroglioma, isocitrate dehydrogenase-mutant and 1 p/19q co-deleted (WHO grade II), managed with surgical resection and radiotherapy. Postoperative brain MRI showed a new enhancing periventricular lesion, making the choice of optimal disease-modifying therapy for MS challenging. This case highlights the possibility of coexistence of MS and oligodendroglioma, and emphasises the importance of a tissue diagnosis when atypical MS imaging features are present. © 2018 BMJ Publishing Group Limited. Published by BMJ.

Author Keywords
multiple sclerosis;  neuroimaging;  neurooncology

Document Type: Article
Source: Scopus

"Entrainment of Circadian Rhythms Depends on Firing Rates and Neuropeptide Release of VIP SCN Neurons" (2018) Neuron

Entrainment of Circadian Rhythms Depends on Firing Rates and Neuropeptide Release of VIP SCN Neurons
(2018) Neuron, . Article in Press. 

Mazuski, C.a , Abel, J.H.b , Chen, S.P.a , Hermanstyne, T.O.a , Jones, J.R.a , Simon, T.a , Doyle, F.J., IIIc , Herzog, E.D.a

a Department of Biology, Washington University in St. Louis, St. Louis, MO, United States
b Department of Systems Biology, Harvard Medical School, Boston, MA, United States
c Harvard John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, United States

Abstract
The mammalian suprachiasmatic nucleus (SCN) functions as a master circadian pacemaker, integrating environmental input to align physiological and behavioral rhythms to local time cues. Approximately 10% of SCN neurons express vasoactive intestinal polypeptide (VIP); however, it is unknown how firing activity of VIP neurons releases VIP to entrain circadian rhythms. To identify physiologically relevant firing patterns, we optically tagged VIP neurons and characterized spontaneous firing over 3 days. VIP neurons had circadian rhythms in firing rate and exhibited two classes of instantaneous firing activity. We next tested whether physiologically relevant firing affected circadian rhythms through VIP release. We found that VIP neuron stimulation with high, but not low, frequencies shifted gene expression rhythms in vitro through VIP signaling. In vivo, high-frequency VIP neuron activation rapidly entrained circadian locomotor rhythms. Thus, increases in VIP neuronal firing frequency release VIP and entrain molecular and behavioral circadian rhythms. Mazuski et al. used optical tagging to characterize the multiday firing activity of neuropeptidergic VIP SCN neurons. They found that increases in VIP neuronal firing frequency entrain circadian rhythms through increased VIP signaling. © 2018 Elsevier Inc.

Author Keywords
channelrhodopsin;  daily oscillation;  multielectrode array;  neuropeptide;  optogenetic;  Period gene;  suprachiasmatic nucleus;  vasoactive intestinal peptide

Document Type: Article in Press
Source: Scopus

"Reduce the burden of dementia now" (2018) Alzheimer's and Dementia

Reduce the burden of dementia now
(2018) Alzheimer’s and Dementia, . Article in Press. 

Hayden, K.M.a , Inouye, S.K.b , Cunningham, C.c , Jones, R.N.d , Avidan, M.e , Davis, D.f , Kuchel, G.g , Khachaturian, A.S.h

a Wake Forest School of Medicine, Winston-Salem, NC, United States
b Beth Israel Deaconess Medical Center, Boston, MA, United States
c Trinity College Dublin, Dublin, Ireland
d Alpert Medical School of Brown University, Providence, RI, United States
e Washington University School of Medicine, St. Louis, MO, United States
f Unit for Lifelong Health and Ageing at UCL, London, United Kingdom
g University of Connecticut Medical Center, West Hartford, CT, United States
h National Biomedical Research Ethics Council, Las Vegas, NV, United States

Document Type: Article in Press
Source: Scopus

"Cuban Epidemic Optic Neuropathy (1991-1993) and José Saramago's Novel Blindness (1995)" (2018) American Journal of Ophthalmology

Cuban Epidemic Optic Neuropathy (1991-1993) and José Saramago’s Novel Blindness (1995)
(2018) American Journal of Ophthalmology, . Article in Press. 

Feibel, R.M.a , Arch, J.b

a Department of Ophthalmology and Visual Sciences, and the Center for History of Medicine, Washington University School of Medicine, St. Louis, Missouri, United States
b Department of English, Washington University, St. Louis, Missouri, United States

Abstract
Purpose: This article reviews the history of Cuban epidemic optic neuropathy (1991-1993), which caused visual loss, peripheral neuralgias, and other neurologic symptoms in over 50,000 persons, an incidence of almost 0.5% of the entire population. The clinical findings, etiology, and treatment are described. We then relate the Cuban epidemic to the fictional epidemic of contagious blindness depicted by Nobel Laureate José Saramago in his 1995 novel Blindness. This novel describes an unnamed modern city in which all inhabitants, except the ophthalmologist’s wife, are affected with a white, not black, blindness. Design: Historical review and literary essay. Methods: The sources for the Cuban epidemic were an extensive review of the published literature and personal communications with physicians who treated these patients. Both authors have analyzed the novel and the critical literature about Saramago’s writings. Results: Though Saramago uses the epidemic of blindness as an allegory to comment on human weakness and immorality, he may also have known of the actual Cuban epidemic. Saramago was a lifelong member of the Communist party, as well as a friend of Fidel Castro and admirer of the Cuban government. We have no proof that Blindness was influenced by the Cuban epidemic, but we find it plausible. Conclusion: It is valuable to examine the real and fictional epidemics side by side, not least because Saramago’s novel depicts the actions of an ophthalmologist during an epidemic of blindness. Ophthalmologists may be interested in a novel that uses the language of eyes, vision, sight, and blindness extensively. © 2018 Elsevier Inc.

Document Type: Article in Press
Source: Scopus