Arts & Sciences Brown School Law McKelvey School of Engineering School of Medicine Weekly Publications

WashU weekly Neuroscience publications

“Hematopoietic stem cell transplantation-induced bone remodeling in autosomal recessive osteopetrosis: Interaction between skeleton and hematopoietic and sensory nervous systems” (2020) Bone

Hematopoietic stem cell transplantation-induced bone remodeling in autosomal recessive osteopetrosis: Interaction between skeleton and hematopoietic and sensory nervous systems
(2020) Bone, 130, art. no. 115144, . 

Maximova, N.a , Zennaro, F.b , Gregori, M.a , Boz, G.c , Zanon, D.a , Mbalaviele, G.d

a Institute for Maternal and Child Health – IRCCS Burlo Garofolo, via dell’Istria 65/1, Trieste, 34137, Italy
b Hôpitaux Pédiatriques de Nice, CHU Lenval, 57 Avenue de la Californie, Nice, 06200, France
c University of Cagliari, Cittadella Universitaria di Monserrato, S. P. Monserrato Sestu Km 0.700 CA, Monserrato, Cagliari 09042, Italy
d Division of Bone and Mineral Diseases, Department of Medicine, Washington University School of Medicine, 660 S. Euclid Ave, CB 8301, St. Louis, MO 63110, United States

Abstract
Objective: Autosomal recessive osteopetrosis (ARO) is a rare congenital disorder of defective bone resorption. The inability of osteoclasts to resorb bone compromises the development of bone marrow cavity, and ultimately, leads to defective hematopoiesis and death within the first decade. The only curative treatment currently available for certain forms of ARO is hematopoietic stem cell transplantation (HSCT). Infants over ten months of age suffering from ARO are defined as patients with advanced disease; HSCT to these patients is associated with high risk of transplant-related mortality (TRM). Because of the extreme variability of ARO clinical phenotypes, the most reliable predictive factor of TRM and graft failure risk is the residual bone marrow space volume. Case report: We report clinical and radiological outcomes of one patient affected by ARO and treated with HSCT at advance stage of the disease. We describe the anomalies in various tissues, including bone marrow and bones at the moment of the diagnosis and document their gradual disappearance after HSCT until their complete resolution based on magnetic resonance imaging (MRI) observations. We provided radiological images of the cranial vault bone structure modifications, correlating the radiological appearance of the optical canals and nerves and of the cerebellum with the neurological manifestations of the disease. Conclusions: Our results demonstrate that MRI is a highly sensitive technique that provides excellent images of bone marrow space before and after HSCT without exposing children to ionizing radiation. MRI also permits us to evaluate post-transplant skeletal remodeling and the deriving changes in the hematopoietic and sensory system. © 2019 Elsevier Inc.

Author Keywords
Autosomal recessive osteopetrosis;  Bone marrow space volume;  Hematopoietic stem cell transplantation;  Magnetic resonance imaging

Document Type: Article
Publication Stage: Final
Source: Scopus

“Deep Learning Analysis of Cerebral Blood Flow to Identify Cognitive Impairment and Frailty in Persons Living With HIV” (2019) Journal of Acquired Immune Deficiency Syndromes (1999)

Deep Learning Analysis of Cerebral Blood Flow to Identify Cognitive Impairment and Frailty in Persons Living With HIV
(2019) Journal of Acquired Immune Deficiency Syndromes (1999), 82 (5), pp. 496-502. 

Luckett, P.a , Paul, R.H.b , Navid, J.a , Cooley, S.A.a , Wisch, J.K.a , Boerwinkle, A.H.a , Tomov, D.a , Ances, B.M.a

a Department of Neurology, Washington University School of Medicine, MI, St. Louis, United States
b Department of Psychological Sciences, University of Missouri Saint Louis, MI, St. Louis, United States

Abstract
BACKGROUND: Deep learning algorithms of cerebral blood flow were used to classify cognitive impairment and frailty in people living with HIV (PLWH). Feature extraction techniques identified brain regions that were the strongest predictors. SETTING: Virologically suppressed (<50 copies/mL) PLWH (n = 125) on combination antiretroviral therapy were enrolled. Participants averaged 51.4 (11.4) years of age and 13.7 (2.8) years of education. Participants were administered a neuropsychological battery, assessed for frailty, and completed structural neuroimaging. METHODS: Deep neural network (DNN) models were trained to classify PLWH as cognitively unimpaired or impaired based on neuropsychological tests (Hopkins Verbal Learning Test-Revised and Brief Visuospatial Memory Test-Revised, Trail making, Letter-Number Sequencing, Verbal Fluency, and Color Word Interference), as well as frail, prefrail, or nonfrail based on the Fried phenotype criteria (at least 3 of the following 5: weight loss, physical inactivity, exhaustion, grip strength, walking time). RESULTS: DNNs classified individuals with cognitive impairment in the learning, memory, and executive domains with 82%-86% accuracy (0.81-0.87 AUC). Our model classified nonfrail, prefrail, and frail PLWH with 75% accuracy. The strongest predictors of cognitive impairment were cortical (parietal, occipital, and temporal) and subcortical (amygdala, caudate, and hippocampus) regions, whereas the strongest predictors of frailty were subcortical (amygdala, caudate, hippocampus, thalamus, pallidum, and cerebellum). CONCLUSIONS: DNN models achieved high accuracy in classifying cognitive impairment and frailty status in PLWH. Feature selection algorithms identified predictive regions in each domain and identified overlapping regions between cognitive impairment and frailty. Our results suggest frailty in HIV is primarily subcortical, whereas cognitive impairment in HIV involves subcortical and cortical brain regions.

Document Type: Article
Publication Stage: Final
Source: Scopus

“Identifying subtypes of cannabis users based on simultaneous polysubstance use” (2019) Drug and Alcohol Dependence

Identifying subtypes of cannabis users based on simultaneous polysubstance use
(2019) Drug and Alcohol Dependence, 205, art. no. 107696, . 

Davis, C.N.a , Slutske, W.S.a , Martin, N.G.b , Agrawal, A.c , Lynskey, M.T.d

a University of Missouri, Department of Psychological Sciences, Columbia, MO 65211, United States
b QIMR Berghofer Medical Research Institute, Brisbane, Queensland 4006, Australia
c Washington University School of Medicine, St. Louis, MO 63110, United States
d King’s College London Institute of Psychiatry, Psychology, & Neuroscience, London, SE5 8BB, United Kingdom

Abstract
Background: Cannabis use patterns vary considerably, with many users reporting simultaneous and non-simultaneous use (co-use) of other substances. Despite this, little research has examined the extent to which subtypes of cannabis users may be identified based on their simultaneous and co-use behaviors. Methods: The sample consisted of adult Australian twins and siblings who reported lifetime cannabis use (n = 2590). A latent class analysis was conducted to determine subtypes of cannabis users based on five indicators of substance co-use and simultaneous use. Adolescent correlates (age of substance initiation and conduct disorder) and adult correlates (substance use/disorder and depression) of class membership were assessed. Twin similarity for class membership was also examined. Results: Four subtypes of users were identified: 1) alcohol co-users, 2) simultaneous alcohol users, 3) simultaneous tobacco users, and 4) simultaneous alcohol, tobacco, and drug users. Compared to co-users of alcohol, simultaneous alcohol users were at increased risk for alcohol problems. Patterns of use that involved simultaneous tobacco and cannabis use (i.e., simultaneous tobacco users and simultaneous alcohol, tobacco, and drug users) were associated with the most problematic outcomes, including substance use and disorder. There was evidence for genetic influences (12–58%) on cannabis use patterns, with higher concordance for latent class membership among monozygotic compared to dizygotic twins (χ2 (1) = 7.19, p = 0.007). Conclusions: The current study identified four classes of cannabis users at varying degrees of risk. Results suggest that simultaneous tobacco and cannabis use may be especially associated with deleterious outcomes. © 2019 Elsevier B.V.

Author Keywords
Cannabis;  Co-use;  Latent class analysis;  Simultaneous polysubstance use

Document Type: Article
Publication Stage: Final
Source: Scopus

“A Comprehensive Resource for Induced Pluripotent Stem Cells from Patients with Primary Tauopathies” (2019) Stem Cell Reports

A Comprehensive Resource for Induced Pluripotent Stem Cells from Patients with Primary Tauopathies
(2019) Stem Cell Reports, 13 (5), pp. 939-955. 

Karch, C.M.a s , Kao, A.W.b m , Karydas, A.b m , Onanuga, K.c , Martinez, R.a s , Argouarch, A.b , Wang, C.d p , Huang, C.d p , Sohn, P.D.d , Bowles, K.R.e , Spina, S.b , Silva, M.C.f , Marsh, J.A.a , Hsu, S.a , Pugh, D.A.e , Ghoshal, N.g , Norton, J.a , Huang, Y.d , Lee, S.E.b , Seeley, W.W.b , Theofilas, P.h , Grinberg, L.T.h , Moreno, F.b , McIlroy, K.c , Boeve, B.F.i , Cairns, N.J.g , Crary, J.F.e j o , Haggarty, S.J.f , Ichida, J.K.k , Kosik, K.S.l q , Miller, B.L.b , Gan, L.d p , Goate, A.M.e n , Temple, S.c , Alquezar, C.m , Bowles, K.n , Butler, D.c , Hernandez, I.q , Hennes, V.k , Kampmann, M.r , Tau Consortium Stem Cell Groupt

a Department of Psychiatry, Washington University in St. Louis School of Medicine, 425 South Euclid Avenue, Campus Box 8134, St. Louis, MO 63110, United States
b Division of Memory and Aging Center, Department of Neurology, University of California, San Francisco, San Francisco, CA 94158, United States
c Neural Stem Cell Institute, 1 Discovery Drive, Rensselaer, NY 12144, United States
d Gladstone Institutes of Neurological Disease, Department of Neurology, Neuroscience Graduate Program, University of California, San Francisco, CA 94158, United States
e Ronald M. Loeb Center for Alzheimer’s Disease, Departments of Neuroscience, Neurology and Genetics & Genomic Sciences, Icahn School of Medicine, New York, NY 10029, United States
f Chemical Neurobiology Laboratory, Center for Genomic Medicine, Departments of Neurology & Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, United States
g Department of Neurology, Washington University in St. Louis, St. Louis, MO 63110, United States
h Department of Pathology and Laboratory Medicine, University of California, San Francisco, San Francisco, CA 94143, United States
i Department of Neurology, Mayo Clinic College of Medicine, Rochester, MN, United States
j Department of Pathology, Fishberg Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States
k Department of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, United States
l Department of Molecular Cellular and Developmental Biology, Neuroscience Research Institute, Biomolecular Science and Engineering Program, University of California, Santa Barbara, Santa Barbara, CA, United States
m Division of Memory and Aging Center, Department of Neurology, University of California, San Francisco, San Francisco, CA 94158, United States
n Ronald M. Loeb Center for Alzheimer’s disease, Depts. of Neuroscience, Neurology and Genetics & Genomic Sciences, Icahn School of Medicine, New York, NY 10029, United States
o Department of Pathology, Fishberg Department of Neuroscience, Friedman Brain Institute, Ronald M. Loeb Center for Alzheimer’s Disease, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States
p Gladstone Institutes of Neurological Disease, Department of Neurology, Neuroscience Graduate Program, University of California, San Francisco, CA 94158, United States
q Department of Molecular Cellular and Developmental Biology, Neuroscience Research Institute, Biomolecular Science and Engineering Program, University of California, Santa Barbara, Santa Barbara, CA, United States
r Department of Biochemistry and Biophysics, Institute for Neurodegenerative Diseases and California Institute for Quantitative Biomedical Research, University of California, San Francisco, CA 94158, United States
s Department of Psychiatry, Washington University in St Louis, St Louis, MO 63110, United States

Abstract
In this article, Karch, Temple and colleagues describe a resource of fibroblasts, patient-derived induced pluripotent stem cells, and genome engineered stem cells with comprehensive clinical histories that can be accessed by the scientific community for disease modeling and development of novel therapeutics for primary tauopathies. © 2019 The Authors

Primary tauopathies are characterized neuropathologically by inclusions containing abnormal forms of the microtubule-associated protein tau (MAPT) and clinically by diverse neuropsychiatric, cognitive, and motor impairments. Autosomal dominant mutations in the MAPT gene cause heterogeneous forms of frontotemporal lobar degeneration with tauopathy (FTLD-Tau). Common and rare variants in the MAPT gene increase the risk for sporadic FTLD-Tau, including progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD). We generated a collection of fibroblasts from 140 MAPT mutation/risk variant carriers, PSP, CBD, and cognitively normal controls; 31 induced pluripotent stem cell (iPSC) lines from MAPT mutation carriers, non-carrier family members, and autopsy-confirmed PSP patients; 33 genome engineered iPSCs that were corrected or mutagenized; and forebrain neural progenitor cells (NPCs). Here, we present a resource of fibroblasts, iPSCs, and NPCs with comprehensive clinical histories that can be accessed by the scientific community for disease modeling and development of novel therapeutics for tauopathies. © 2019 The Authors

Author Keywords
corticobasal degeneration;  CRISPR/Cas9;  fibroblasts;  frontotemporal dementia;  induced pluripotent stem cells;  MAPT;  neural progenitor cells;  progressive supranuclear palsy;  tau;  tauopathy

Document Type: Article
Publication Stage: Final
Source: Scopus
Access Type: Open Access

“Chromatin Environment and Cellular Context Specify Compensatory Activity of Paralogous MEF2 Transcription Factors” (2019) Cell Reports

Chromatin Environment and Cellular Context Specify Compensatory Activity of Paralogous MEF2 Transcription Factors
(2019) Cell Reports, 29 (7), pp. 2001-2015.e5. 

Majidi, S.P.a b , Reddy, N.C.a , Moore, M.J.a , Chen, H.a , Yamada, T.a c , Andzelm, M.M.f , Cherry, T.J.d f e f , Hu, L.S.f , Greenberg, M.E.f , Bonni, A.a

a Department of Neuroscience, Washington University School of Medicine, St. Louis, MO 63110, United States
b MD-PhD Program, Washington University School of Medicine, St. Louis, MO 63110, United States
c Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan
d Department of Pediatrics, University of Washington School of Medicine, Seattle, WA 98101, United States
e Center for Developmental Biology and Regenerative Medicine, Seattle Children’s Research Institute, 1900 9<sup>th</sup> Ave., Seattle, WA 98101, United States
f Department of Neurobiology, Harvard Medical School, Boston, MA 02115, United States

Abstract
Compensation among paralogous transcription factors (TFs) confers genetic robustness of cellular processes, but how TFs dynamically respond to paralog depletion on a genome-wide scale in vivo remains incompletely understood. Using single and double conditional knockout of myocyte enhancer factor 2 (MEF2) family TFs in granule neurons of the mouse cerebellum, we find that MEF2A and MEF2D play functionally redundant roles in cerebellar-dependent motor learning. Although both TFs are highly expressed in granule neurons, transcriptomic analyses show MEF2D is the predominant genomic regulator of gene expression in vivo. Strikingly, genome-wide occupancy analyses reveal upon depletion of MEF2D, MEF2A occupancy robustly increases at a subset of sites normally bound to MEF2D. Importantly, sites experiencing compensatory MEF2A occupancy are concentrated within open chromatin and undergo functional compensation for genomic activation and gene expression. Finally, motor activity induces a switch from non-compensatory to compensatory MEF2-dependent gene regulation. These studies uncover genome-wide functional interdependency between paralogous TFs in the brain. © 2019 The Authors

Majidi et al. study how transcription factors respond to paralog depletion by conditionally depleting MEF2A and MEF2D in mouse cerebellum. Depletion of MEF2D induces functionally compensatory genomic occupancy by MEF2A. Compensation occurs within accessible chromatin in a context-dependent manner. This study explores the interdependency between paralogous transcription factors. © 2019 The Authors

Author Keywords
cerebellum;  chromatin;  chromatin accessibility;  compensation;  gene expression;  interdependency;  learning;  MEF2;  neuron;  paralog;  transcription factor

Document Type: Article
Publication Stage: Final
Source: Scopus
Access Type: Open Access

“Steady-state activation of the high-affinity isoform of the α4β2δ GABAA receptor” (2019) Scientific Reports

Steady-state activation of the high-affinity isoform of the α4β2δ GABAA receptor
(2019) Scientific Reports, 9 (1), art. no. 15997, . 

Pierce, S.R.a , Senneff, T.C.a , Germann, A.L.a , Akk, G.a b

a Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO 63110, United States
b The Taylor Family Institute for Innovative Psychiatric Research, Washington University School of Medicine, St. Louis, MO 63110, United States

Abstract
Activation of GABAA receptors consisting of α4, β2 (or β3), and δ subunits is a major contributor to tonic inhibition in several brain regions. The goal of this study was to analyze the function of the α4β2δ receptor in the presence of GABA and other endogenous and clinical activators and modulators under steady-state conditions. We show that the receptor has a high constitutive open probability (~0.1), but is only weakly activated by GABA that has a maximal peak open probability (POpen,peak) of 0.4, taurine (maximal POpen,peak = 0.4), or the endogenous steroid allopregnanolone (maximal POpen,peak = 0.2). The intravenous anesthetic propofol is a full agonist (maximal POpen,peak = 0.99). Analysis of currents using a cyclic three-state Resting-Active-Desensitized model indicates that the maximal steady-state open probability of the α4β2δ receptor is ~0.45. Steady-state open probability in the presence of combinations of GABA, taurine, propofol, allopregnanolone and/or the inhibitory steroid pregnenolone sulfate closely matched predicted open probability calculated assuming energetic additivity. The results suggest that the receptor is active in the presence of physiological concentrations of GABA and taurine, but, surprisingly, that receptor activity is only weakly potentiated by propofol. © 2019, The Author(s).

Document Type: Article
Publication Stage: Final
Source: Scopus
Access Type: Open Access

“Microglia drive APOE-dependent neurodegeneration in a tauopathy mouse model” (2019) The Journal of Experimental Medicine

Microglia drive APOE-dependent neurodegeneration in a tauopathy mouse model
(2019) The Journal of Experimental Medicine, 216 (11), pp. 2546-2561. 

Shi, Y.a , Manis, M.a , Long, J.a , Wang, K.a , Sullivan, P.M.b , Remolina Serrano, J.a , Hoyle, R.a , Holtzman, D.M.a

a Department of Neurology, Hope Center for Neurological Disorders, Charles F. and Joanne Knight Alzheimer’s Disease Research Center, Washington University School of Medicine, St. Louis, MO
b Department of Medicine, Duke University School of Medicine, Durham

Abstract
Chronic activation of brain innate immunity is a prominent feature of Alzheimer’s disease (AD) and primary tauopathies. However, to what degree innate immunity contributes to neurodegeneration as compared with pathological protein-induced neurotoxicity, and the requirement of a particular glial cell type in neurodegeneration, are still unclear. Here we demonstrate that microglia-mediated damage, rather than pathological tau-induced direct neurotoxicity, is the leading force driving neurodegeneration in a tauopathy mouse model. Importantly, the progression of ptau pathology is also driven by microglia. In addition, we found that APOE, the strongest genetic risk factor for AD, regulates neurodegeneration predominantly by modulating microglial activation, although a minor role of apoE in regulating ptau and insoluble tau formation independent of its immunomodulatory function was also identified. Our results suggest that therapeutic strategies targeting microglia may represent an effective approach to prevent disease progression in the setting of tauopathy. © 2019 Shi et al.

Document Type: Article
Publication Stage: Final
Source: Scopus
Access Type: Open Access

“Understanding a complicated Gal-1” (2019) Neuro-Oncology

Understanding a complicated Gal-1
(2019) Neuro-Oncology, 21 (11), pp. 1341-1343. 

Hirbe, A.C.a , Gutmann, D.H.b

a Division of Medical Oncology, Department of Medicine, Washington University, School of Medicine, Campus Box 8076, 660 S. Euclid Avenue, St Louis, MO, United States
b Department of Neurology, Washington University, School of Medicine, St Louis, MO, United States

Document Type: Editorial
Publication Stage: Final
Source: Scopus

“What are the threats to successful brain and cognitive aging?” (2019) Neurobiology of Aging

What are the threats to successful brain and cognitive aging?
(2019) Neurobiology of Aging, 83, pp. 130-134. 

Gallagher, M.a , Okonkwo, O.C.b , Resnick, S.M.c , Jagust, W.J.d , Benzinger, T.L.S.e , Rapp, P.R.c

a Department of Psychological and Brain Sciences, Johns Hopkins University, Baltimore, MD, United States
b Department of Medicine and Alzheimer’s Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, United States
c Laboratory of Behavioral Neuroscience, National Institute on Aging, Baltimore, MD, United States
d Helen Wills Neuroscience Institute, University of California, Berkeley, CA, United States
e Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO, United States

Abstract
The structure and function of the brain change over the life span. Aged brains often accumulate pathologic lesions, such as amyloid plaques and tau tangles, which lead to diminished cognitive ability in some, but not all, individuals. The basis of this vulnerability and resilience is unclear. Age-related changes can alter neural firing patterns and ability to form new memories. Risk factors for cognitive decline include male sex and apolipoprotein E genotype. Physical activity seems to be protective against cognitive decline. Longitudinal studies have shown that, although the onset of amyloid pathology and associated cognitive decline can vary greatly, once it begins, the rate of deposition is similar among affected individuals. This session of the Cognitive Aging Summit III explored fixed and modifiable factors that can threaten cognitive function in aging adults and approaches to modulate at least some of these risks. © 2019

Author Keywords
Compensation;  Maintenance;  Modifiable factors;  Pathology;  Reserve;  Resilience

Document Type: Article
Publication Stage: Final
Source: Scopus

“Mechanically transformative electronics, sensors, and implantable devices” (2019) Science Advances

Mechanically transformative electronics, sensors, and implantable devices
(2019) Science Advances, 5 (11), art. no. eaay0418, . 

Byun, S.-H.a , Sim, J.Y.b , Zhou, Z.c , Lee, J.a , Qazi, R.a d , Walicki, M.C.e f g h , Parker, K.E.e f g h , Haney, M.P.d , Choi, S.H.a , Shon, A.d , Gereau, G.B.e f g h , Bilbily, J.e f g h i , Li, S.j , Liu, Y.d , Yeo, W.-H.k , McCall, J.G.e f g h , Xiao, J.c , Jeong, J.-W.a d

a School of Electrical Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, 34141, South Korea
b Welfare and Medical ICT Research Department, Electronics and Telecommunications Research Institute, Daejeon, 34129, South Korea
c Department of Mechanical Engineering, University of Colorado Boulder, Boulder, CO 80309, United States
d Department of Electrical, Computer, and Energy Engineering, University of Colorado Boulder, Boulder, CO 80309, United States
e Department of Anesthesiology, Washington University in St. Louis, St. Louis, MO 63110, United States
f Depart-ment of Pharmaceutical and Administrative Sciences, St. Louis College of Pharmacy, St. Louis, MO 63110, United States
g Center for Clinical Pharmacology, St. Louis College of Pharmacy, Washington University School of Medicine, St. Louis, MO 63110, United States
h Washington University Pain Center, Washington University in St. Louis, St. Louis, MO 63110, United States
i Department of Psychiatry, Washington University in St. Louis, St. Louis, MO 63110, United States
j Department of Materials Science and Engineering, Cornell University, Ithaca, NY 14853, United States
k George W. Woodruff School of Mechanical Engineering and, Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA 30332, United States

Abstract
Traditionally, electronics have been designed with static form factors to serve designated purposes. This approach has been an optimal direction for maintaining the overall device performance and reliability for targeted applications. However, electronics capable of changing their shape, flexibility, and stretchability will enable versatile and accommodating systems for more diverse applications. Here, we report design concepts, materials, physics, and manufacturing strategies that enable these reconfigurable electronic systems based on temperature-triggered tuning of mechanical characteristics of device platforms. We applied this technology to create personal electronics with variable stiffness and stretchability, a pressure sensor with tunable bandwidth and sensitivity, and a neural probe that softens upon integration with brain tissue. Together, these types of transformative electronics will substantially broaden the use of electronics for wearable and implantable applications. Copyright © 2019 The Authors, some rights reserved;

Document Type: Article
Publication Stage: Final
Source: Scopus
Access Type: Open Access

“Factor Structure of the Disabilities of the Arm, Shoulder and Hand Questionnaire in Upper Extremity Nerve Injury” (2019) Plastic and Reconstructive Surgery

Factor Structure of the Disabilities of the Arm, Shoulder and Hand Questionnaire in Upper Extremity Nerve Injury
(2019) Plastic and Reconstructive Surgery, 144 (5), pp. 1116-1122. 

Novak, C.B., Mackinnon, S.E., Anastakis, D.J., McCabe, S.J.

Toronto, Ontario, Canada; and St. Louis, Mo. From the Division of Plastic and Reconstructive Surgery, University of Toronto; and the Division of Plastic and Reconstructive Surgery, Washington University School of Medicine

Abstract
BACKGROUND: This study evaluated the validity of the factor structure of the Disabilities of the Arm, Shoulder and Hand questionnaire to assess upper extremity disability in patients with upper extremity nerve injury. METHODS: Data were used from previous cross-sectional studies of patients with upper extremity nerve injuries. Research ethics approval was obtained for secondary data analyses. Descriptive and factor analyses were performed. RESULTS: Patients (n = 242; 170 men and 72 women) with upper extremity nerve injury included distal nerve (n = 131), brachial plexus (n = 88), and single proximal shoulder nerve (n = 23). The mean Disabilities of the Arm, Shoulder and Hand questionnaire score was 47.3 ± 22. For the questionnaire, a three-factor structure had the highest variance and no overlap between factors. The factors related to (1) light effort tasks, (2) greater effort tasks, and (3) work/social activity limitations and pain. Brachial plexus injuries had significantly higher overall questionnaire scores compared to distal and single proximal nerve injuries. The light effort factor scores were significantly lower in single proximal nerve injuries compared with brachial plexus and distal nerve injuries. Nondominant compared to dominant hand involvement revealed no difference in overall questionnaire scores but significantly higher dominant hand scores in the light effort factor (p = 0.001). CONCLUSIONS: In patients with nerve injury, the factor analysis of the Disabilities of the Arm, Shoulder and Hand questionnaire indicated a multifactor construct. These domains should be considered when using the questionnaire and may be helpful to assess disability related to specific tasks in different nerve injuries and with dominant hand involvement.

Document Type: Article
Publication Stage: Final
Source: Scopus

“The Impact of the Geometric Correction Scheme on MEG Functional Topology at Rest” (2019) Frontiers in Neuroscience

The Impact of the Geometric Correction Scheme on MEG Functional Topology at Rest
(2019) Frontiers in Neuroscience, 13, art. no. 1114, . 

Della Penna, S.a , Corbetta, M.b c , Wens, V.d e , de Pasquale, F.f

a Department of Neuroscience, Imaging and Clinical Sciences, and Institute for Advanced Biomedical Technologies, “G. d’Annunzio” University of Chieti-Pescara, Chieti, Italy
b Department of Neuroscience and Padova Neuroscience Center, University of Padua, Padua, Italy
c Department of Neurology, Radiology, and Anatomy and Neurobiology, Washington University, St. Louis, MO, United States
d Laboratoire de Cartographie Fonctionnelle du Cerveau, UNI—ULB Neuroscience Institute, Université Libre de Bruxelles, Brussels, Belgium
e Magnetoencephalography Unit, Department of Functional Neuroimaging, Service of Nuclear Medicine, CUB—Hôpital Erasme, Brussels, Belgium
f Faculty of Veterinary Medicine, University of Teramo, Teramo, Italy

Abstract
Spontaneous activity is correlated across brain regions in large scale networks (RSN) closely resembling those recruited during several behavioral tasks and characterized by functional specialization and dynamic integration. Specifically, MEG studies revealed a set of central regions (dynamic core) possibly facilitating communication among differently specialized brain systems. However, source projected MEG signals, due to the fundamentally ill-posed inverse problem, are affected by spatial leakage, leading to the estimation of spurious, blurred connections that may affect the topological properties of brain networks and their integration. To reduce leakage effects, several correction schemes have been proposed including the Geometric Correction Scheme (GCS) whose theory, simulations and empirical results on topography of a few RSNs were already presented. However, its impact on the estimation of fundamental graph measures used to describe the architecture of interactions among brain regions has not been investigated yet. Here, we estimated dense, MEG band-limited power connectomes in theta, alpha, beta, and gamma bands from 13 healthy subjects (all young adults). We compared the connectivity and topology of MEG uncorrected and GCS-corrected connectomes. The use of GCS considerably reorganized the topology of connectivity, reducing the local, within-hemisphere interactions mainly in the beta and gamma bands and increasing across-hemisphere interactions mainly in the alpha and beta bands. Moreover, the number of hubs decreased in the alpha and beta bands, but the centrality of some fundamental regions such as the Posterior Cingulate Cortex (PCC), Supplementary Motor Area (SMA) and Middle Prefrontal Cortex (MPFC) remained strong in all bands, associated to an increase of the Global Efficiency and a decrease of Modularity. As a comparison, we applied orthogonalization on connectomes and ran the same topological analyses. The correlation values were considerably reduced, and orthogonalization mainly decreased local within-hemisphere interactions in all bands, similarly to GCS. Notably, the centrality of the PCC, SMA and MPFC was preserved in all bands, as for GCS, together with other hubs in the posterior parietal regions. Overall, leakage correction removes spurious local connections, but confirms the role of dynamic hub regions, specifically the anterior and posterior cingulate, in integrating information in the brain at rest. © Copyright © 2019 Della Penna, Corbetta, Wens and de Pasquale.

Author Keywords
band-limited power correlation;  functional connectivity;  functional hubs;  leakage correction;  MEG connectome

Document Type: Article
Publication Stage: Final
Source: Scopus
Access Type: Open Access

“Developing a Spatial Navigation Screening Tool Sensitive to the Preclinical Alzheimer Disease Continuum” (2019) Archives of Clinical Neuropsychology : the Official Journal of the National Academy of Neuropsychologists

Developing a Spatial Navigation Screening Tool Sensitive to the Preclinical Alzheimer Disease Continuum
(2019) Archives of Clinical Neuropsychology : the Official Journal of the National Academy of Neuropsychologists, 34 (7), pp. 1138-1155. 

Allison, S.L.a , Rodebaugh, T.L.a , Johnston, C.a , Fagan, A.M.b c d , Morris, J.C.b d , Head, D.a b e

a Department of Psychological and Brain Sciences, Washington University in St. Louis, St. Louis, MO, United States
b Knight Alzheimer Disease Research Center, Washington University in St. Louis, St. Louis, MO, United States
c Hope Center for Neurological Disorders, Washington University in St. Louis, St. Louis, MO, United States
d Neurology Department, Washington University in St. Louis, St. Louis, MO, United States
e Radiology Department, Washington University in St. Louis, St. Louis, MO, United States

Abstract
OBJECTIVE: There remains a need for a non-invasive and cost-effective screening measure that could be administered prior to the provision of a lumbar puncture or positron emission tomography scan for the detection of preclinical Alzheimer disease (AD). Previous findings suggest that a hippocampally-based spatial navigation task may be effective for screening individuals for the preclinical AD continuum (i.e., low cerebrospinal fluid (CSF) Aβ42). Unfortunately, this task took 1.5-2 hours to administer, which would be time-prohibitive in a clinical setting. Therefore, the goal of this study was to compare psychometric properties of six spatial navigation-related tasks in order to take the next steps in developing a clinically appropriate screening measure. METHODS: Psychometric properties (i.e., reliability, diagnostic accuracy, validity) of a modified version of the cognitive mapping task, two binding tasks, a visual perspective taking task, and self- and informant report versions of a questionnaire were examined in a sample of 91 clinically normal (CN) individuals. CSF Aβ42 and ptau181 were available for 30 individuals. RESULTS: The learning phase of the cognitive mapping task and the self-report questionnaire were sensitive to identifying individuals in the preclinical AD continuum (93% and 87% sensitivity, 60% and 67% specificity, respectively). These two measures also demonstrated good test-retest stability (intraclass correlation coefficients = .719 and .838, respectively) and internal consistency (Cronbach’s αs = .825 and .965, respectively). CONCLUSIONS: These findings suggest that a self-report questionnaire and aspects of a cognitive mapping task may be particularly appropriate for development as screening tools for identifying individuals in the preclinical AD continuum. © The Author(s) 2019. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Author Keywords
amyloid;  cognition;  hippocampus;  ptau;  reliability;  validity

Document Type: Article
Publication Stage: Final
Source: Scopus

“NPY2R signaling gates spontaneous and mechanical, but not thermal, pain transmission” (2019) Molecular Pain

NPY2R signaling gates spontaneous and mechanical, but not thermal, pain transmission
(2019) Molecular Pain, 15, pp. 1744806919887830. 

Chen, S.a b c , Liu, X.-Y.b c , Jiao, Y.a , Chen, Z.-F.b c d e , Yu, W.a

a Department of Anesthesiology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong UniversityShanghai, China
b Center for the Study of Itch, Washington University School of Medicine, St. Louis, MO, USA
c Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO, USA
d Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA
e Department of Developmental Biology, Washington University School of Medicine, St. Louis, MO, USA

Author Keywords
NPY;  pain;  spinal cord;  Y1R;  Y2R

Document Type: Article
Publication Stage: Final
Source: Scopus
Access Type: Open Access

“Examining associations between two different jumping to conclusions scores with positive schizotypy and recent distress” (2019) Cognitive Neuropsychiatry

Examining associations between two different jumping to conclusions scores with positive schizotypy and recent distress
(2019) Cognitive Neuropsychiatry, . 

Hua, J.P.Y.a , Karcher, N.R.a b , Kerns, J.G.a

a Department of Psychological Sciences, University of Missouri, Columbia, MO, United States
b Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, United States

Abstract
Introduction: Jumping to conclusions is associated with delusions. It is unclear whether positive schizotypy, which refers to delusion-like and hallucination-like symptoms, is associated with jumping to conclusions. Relatedly, the relative validity of two jumping to conclusions scores, extreme responding and draws to decision, is unclear, particularly whether extreme responding (responding after one or two draws) reflects the same bias as decreased draws to decision on non-extreme responding trials. Methods: Extreme positive schizotypy individuals with increased psychosis risk (n = 69) and controls (n = 95) completed the Probabilistic Reasoning Task and reported on recent distress, which was previously associated with jumping to conclusions. We calculated extreme responding, draws to decision (number of draws), and draws to decision/non-extreme responding (number of draws on trials with three or more draws). Results: Positive schizotypy was associated with extreme responding, but not draws to decision/non-extreme responding. Furthermore, draws to decision and draws to decision/non-extreme responding were associated with recent distress, whereas extreme responding was not. Conclusion: Positive schizotypy was specifically associated with extreme responding and not draws to decision/non-extreme responding, which suggests that the nature of extreme responding and of draws to decision might be different. This could have relevance for assessing and treating jumping to conclusions. © 2019, © 2019 Informa UK Limited, trading as Taylor & Francis Group.

Author Keywords
cognitive bias;  draws to decision;  Extreme responding;  magical ideation;  psychosis risk

Document Type: Article
Publication Stage: Article in Press
Source: Scopus

“Sibling comparisons elucidate the associations between educational attainment polygenic scores and alcohol, nicotine and cannabis” (2019) Addiction

Sibling comparisons elucidate the associations between educational attainment polygenic scores and alcohol, nicotine and cannabis
(2019) Addiction, . 

Salvatore, J.E.a b , Barr, P.B.a , Stephenson, M.a , Aliev, F.a c , Kuo, S.I.-C.a , Su, J.d , Agrawal, A.e , Almasy, L.f g , Bierut, L.e , Bucholz, K.e , Chan, G.h , Edenberg, H.J.i , Johnson, E.C.e , McCutcheon, V.V.e , Meyers, J.L.j , Schuckit, M.k , Tischfield, J.l , Wetherill, L.m , Dick, D.M.a n o

a Department of Psychology, Virginia Commonwealth University, Richmond, VA, United States
b Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA, United States
c Department of Business Administration, Karabuk University, Karabuk, Turkey
d Department of Psychology, Arizona State University, Tempe, AZ, United States
e Department of Psychiatry, Washington University, St Louis, MO, United States
f Department of Genetics, University of Pennsylvania, Philadelphia, PA, United States
g Department of Biomedical and Health Informatics, Children’s Hospital of Philadelphia, Philadelphia, PA, United States
h Department of Psychiatry, University of Connecticut School of Medicine, Farmington, CT, United States
i Department of Biochemistry and Molecular Biology, Indiana University, Indianapolis, IN, United States
j Department of Psychiatry, SUNY Downstate Medical Center, Brooklyn, NY, United States
k Department of Psychiatry, University of California–San Diego, La Jolla, CA, United States
l Department of Genetics and the Human Genetics Institute of New Jersey, Piscataway, NJ, United States
m Department of Medical and Molecular Genetics, Indiana University, Indianapolis, IN, United States
n Department of Human and Molecular Genetics, Virginia Commonwealth University, Richmond, VA, United States
o College Behavioral and Emotional Health Institute, Virginia Commonwealth University, Richmond, VA, United States

Abstract
Background and Aims: The associations between low educational attainment and substance use disorders (SUDs) may be related to a common genetic vulnerability. We aimed to elucidate the associations between polygenic scores for educational attainment and clinical criterion counts for three SUDs (alcohol, nicotine and cannabis). Design: Polygenic association and sibling comparison methods. The latter strengthens inferences in observational research by controlling for confounding factors that differ between families. Setting: Six sites in the United States. Participants: European ancestry participants aged 25 years and older from the Collaborative Study on the Genetics of Alcoholism (COGA). Polygenic association analyses included 5582 (54% female) participants. Sibling comparisons included 3098 (52% female) participants from 1226 sibling groups nested within the overall sample. Measurements: Outcomes included criterion counts for DSM-5 alcohol use disorder (AUDSX), Fagerström nicotine dependence (NDSX) and DSM-5 cannabis use disorder (CUDSX). We derived polygenic scores for educational attainment (EduYears-GPS) using summary statistics from a large (&gt; 1 million) genome-wide association study of educational attainment. Findings: In polygenic association analyses, higher EduYears-GPS predicted lower AUDSX, NDSX and CUDSX [P &lt; 0.01, effect sizes (R2) ranging from 0.30 to 1.84%]. These effects were robust in sibling comparisons, where sibling differences in EduYears-GPS predicted all three SUDs (P &lt; 0.05, R2 0.13–0.20%). Conclusions: Individuals who carry more alleles associated with educational attainment tend to meet fewer clinical criteria for alcohol, nicotine and cannabis use disorders, and these effects are robust to rigorous controls for potentially confounding factors that differ between families (e.g. socio-economic status, urban–rural residency and parental education). © 2019 Society for the Study of Addiction

Author Keywords
Alcohol;  cannabis;  Collaborative Study on the Genetics of Alcoholism;  nicotine;  polygenic risk score;  sibling comparisons

Document Type: Article
Publication Stage: Article in Press
Source: Scopus

“Using Xenopus oocytes in neurological disease drug discovery” (2019) Expert Opinion on Drug Discovery

Using Xenopus oocytes in neurological disease drug discovery
(2019) Expert Opinion on Drug Discovery, . 

Zeng, S.L., Sudlow, L.C., Berezin, M.Y.

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

Abstract
Introduction: Neurological diseases present a difficult challenge in drug discovery. Many of the current treatments have limited efficiency or result in a variety of debilitating side effects. The search of new therapies is of a paramount importance, since the number of patients that require a better treatment is growing rapidly. As an in vitro model, Xenopus oocytes provide the drug developer with many distinct advantages, including size, durability, and efficiency in exogenous protein expression. However, there is an increasing need to refine the recent breakthroughs. Areas covered: This review covers the usage and recent advancements of Xenopus oocytes for drug discovery in neurological diseases from expression and functional measurement techniques to current applications in Alzheimer’s disease, painful neuropathies, and amyotrophic lateral sclerosis (ALS). The existing limitations of Xenopus oocytes in drug discovery are also discussed. Expert opinion: With the rise of aging population and neurological disorders, Xenopus oocytes, will continue to play an important role in understanding the mechanism of the disease, identification and validation of novel molecular targets, and drug screening, providing high-quality data despite the technical limitations. With further advances in oocytes-related techniques toward an accurate modeling of the disease, the diagnostics and treatment of neuropathologies will be becoming increasing personalized. © 2019, © 2019 Informa UK Limited, trading as Taylor & Francis Group.

Author Keywords
ALS;  Alzheimer;  chronic pain;  CIPN;  electrophysiology;  ion channels;  neurological diseases;  patch clamping;  Xenopus oocytes

Document Type: Review
Publication Stage: Article in Press
Source: Scopus

“The effect of living in communal homes on the depressive symptoms of older women living in rural areas: the mediating role of the socio-physical environment” (2019) Journal of Women and Aging

The effect of living in communal homes on the depressive symptoms of older women living in rural areas: the mediating role of the socio-physical environment
(2019) Journal of Women and Aging, . 

Lee, H.a , Park, S.b , Changu, L.c

a Department of Social Welfare, Daegu University, Gyeongsan-si, South Korea
b Brown School of Social Work, Washington University in Saint Louis, Saint Louis, MO, United States
c Heungdeok Community Welfare CenterMunkyung-si, South Korea

Abstract
This study examined the effects of the village communal living model on depressive symptoms, focusing on mediating roles of perceived environment among rural older women in South Korea. Data came from the sample of residents in 18 housings and their peers in the conventional housing (n = 168). Propensity score analysis and structural equation modeling were used. The results showed the effect of living in VCH on depressive symptoms was mediated distinct aspect of socio-physical environment. © 2019, © 2019 Taylor & Francis.

Author Keywords
depressive symptoms;  perceived environment;  Rural aging;  senior housing

Document Type: Article
Publication Stage: Article in Press
Source: Scopus

“Aging and strategic prospective memory monitoring” (2019) Memory and Cognition

Aging and strategic prospective memory monitoring
(2019) Memory and Cognition, . 

Ball, B.H.a b , Li, Y.P.b , Bugg, J.M.b

a Department of Psychology, University of Texas at Arlington, 501 Nedderman Drive, Arlington, TX 76109, United States
b Department of Psychological and Brain Sciences, Washington University in St. Louis, CB1125, One Brookings Dr, St. Louis, MO 63130, United States

Abstract
Monitoring the environment for the occurrence of prospective memory (PM) targets is a resource-demanding process that produces cost (e.g., slowing) to ongoing activities. Prior research has shown that older adults are able to monitor strategically, which involves the activation of monitoring when contextually appropriate and deactivation of monitoring when it is not thereby affording conservation of limited-capacity attentional resources. However, the time course and efficiency with which these processes operate with increased age are unknown. In the current study, participants performed an ongoing lexical decision task in which words/nonwords were blocked by font color in sets of ten trials (ten red trials followed by ten blue trials). Importantly, participants were informed that PM targets (“TOR” syllable) would only occur in red trials. Replicating previous work, both younger and older adults were successfully able to disengage monitoring upon encountering the unexpected (i.e., blue) context. However, while younger adults completely disengaged monitoring in the unexpected context, older adults continued to show monitoring across the majority of trials. Additionally, younger, but not older, adults showed a re-engagement of monitoring at the end of the unexpected context in preparation for the upcoming expected context. These findings suggest that while strategic monitoring generally remains intact with increased age, the disengagement and preparatory re-engagement of strategic monitoring may operate less optimally for older adults. However, while younger adults completely disengaged monitoring in the unexpected context, older adults continued to show monitoring across the majority of trials. Additionally, younger, but not older, adults showed a re-engagement of monitoring at the end of the unexpected context in preparation for the upcoming expected context. These findings suggest that while strategic monitoring generally remains intact with increased age, the disengagement and preparatory re-engagement of strategic monitoring may operate less optimally for older adults. © 2019, The Psychonomic Society, Inc.

Author Keywords
Aging;  Attention;  Context;  Prospective memory;  Strategic monitoring

Document Type: Article
Publication Stage: Article in Press
Source: Scopus

“Emotion Identification in Preschool and Early Adolescent Body Mass Index: Exploring the Roles of Depressive Symptoms and Peer Relations” (2019) Child Psychiatry and Human Development

Emotion Identification in Preschool and Early Adolescent Body Mass Index: Exploring the Roles of Depressive Symptoms and Peer Relations
(2019) Child Psychiatry and Human Development, . 

Pine, A.a , Barch, D.M.b c d e , Luby, J.b , Whalen, D.J.b

a Department of Psychology and Human Development, Vanderbilt University, 230 Appleton Place, Nashville, TN 37203, United States
b Department of Psychiatry, Washington University School of Medicine, 4444 Forest Park, Suite 2100, St. Louis, MO 63108, United States
c Department of Psychological & Brain Sciences, Washington University, 1 Brookings Drive, St. Louis, MO 63130, United States
d The Program in Neuroscience, Washington University in St. Louis, St. Louis, United States
e Department of Radiology, Washington University School of Medicine in St. Louis, St. Louis, United States

Abstract
The ability to identify and label emotions may represent an early-life risk factor that relates to excess weight gain during childhood. The current study investigates the relationships between preschool emotion identification and early adolescent body mass index (BMI), as well as the mediating role of two variables: depressive symptoms and peer relations. In a longitudinal study, preschoolers completed an emotion identification task, and parents completed psychiatric assessments and a peer-relations questionnaire about their child. BMI percentile was measured at later time points in early adolescence. Poor emotion identification during preschool predicted increases in BMI percentile over time, with greater deficits in emotion identification ability relating to steeper increases in BMI percentile across early adolescence. Peer relations in preschool partially mediated the relationship between preschool emotion identification ability and adolescent BMI. This study provides novel information about potential targets for early interventions in the service of obesity prevention. © 2019, Springer Science+Business Media, LLC, part of Springer Nature.

Author Keywords
Depression;  Emotion identification;  Obesity;  Peer relations;  Preschool

Document Type: Article
Publication Stage: Article in Press
Source: Scopus

“POLR1B and neural crest cell anomalies in Treacher Collins syndrome type 4” (2019) Genetics in Medicine

POLR1B and neural crest cell anomalies in Treacher Collins syndrome type 4
(2019) Genetics in Medicine, . 

Sanchez, E.a b , Laplace-Builhé, B.b , Mau-Them, F.T.a b c d , Richard, E.e , Goldenberg, A.f , Toler, T.L.g , Guignard, T.h , Gatinois, V.h , Vincent, M.i , Blanchet, C.j , Boland, A.k , Bihoreau, M.T.k , Deleuze, J.-F.k , Olaso, R.k , Nephi, W.g , Lüdecke, H.-J.l , Verheij, J.B.G.M.m , Moreau-Lenoir, F.n , Denoyelle, F.o , Rivière, J.-B.p , Laplanche, J.-L.q , Willing, M.g , Captier, G.r , Apparailly, F.b , Wieczorek, D.l , Collet, C.q , Djouad, F.b , Geneviève, D.a b

a Service de Génétique Clinique, centre de référence anomalies du développement et syndromes malformatifs, Département de Génétique Médicale, Maladies Rares et Médecine Personnalisée, Hôpital Arnaud de Villeneuve, Faculté de Médecine, Montpellier, France
b IRMB, Univ Montpellier, INSERM, CHU Montpellier, Montpellier, France
c Unité Fonctionnelle d’Innovation diagnostique des maladies rares, Pôle de Biologie, FHU-TRANSLAD, CHU Dijon Bourgogne, Dijon, France
d Inserm–Université de Bourgogne UMR1231 GAD, FHU-TRANSLAD, Dijon, France
e IRCM, INSERM, U1194 Univ Montpellier, Montpellier, France
f Normandie Univ, UNIROUEN, Inserm U1245 and Rouen University Hospital, Department of Genetics, F 76000, Normandy Center for Genomic and Personalized Medicine, Reference Center for Developmental Disorders, Rouen, France
g Department of Pediatrics, Division of Genetics & Genomic Medicine, Washington University School of Medicine, St. Louis, MO, United States
h Unité de Génétique Chromosomique, Plateforme ChromoStem, Hôpital Arnaud de Villeneuve, CHU Montpellier, Montpellier, France
i Service de génétique médicale, CHU de Nantes, Nantes, France
j Service ORL, Montpellier, France
k Centre National de Recherche en Génomique Humaine (CNRGH), Institut de Biologie François Jacob, CEA, Université Paris-Saclay, Evry, France
l Institute of Human Genetics, Medical Faculty, Heinrich Heine University, Düsseldorf, Germany
m Department of Medical Genetics, University Medical Centre Groningen, University of Groningen, Groningen, Netherlands
n ORL CH d’Evreux, Évreux, France
o Service d’ORL pédiatrique, Hôpital Universitaire Necker-Enfants Malades, APHP et François Jacob, CEA, Université Paris-Saclay, Evry, France
p Laboratoire de Génétique Moléculaire, Plateau technique de Biologie – CHU Dijon, Dijon, France
q UF de Génétique Moléculaire, Service de Biochimie et Biologie Moléculaire, Hôpital Lariboisière, Paris, France
r Chirurgie plastique infantile Montpellier, Montpellier, France

Abstract
Purpose: Treacher Collins syndrome (TCS) is a rare autosomal dominant mandibulofacial dysostosis, with a prevalence of 0.2–1/10,000. Features include bilateral and symmetrical malar and mandibular hypoplasia and facial abnormalities due to abnormal neural crest cell (NCC) migration and differentiation. To date, three genes have been identified: TCOF1, POLR1C, and POLR1D. Despite a large number of patients with a molecular diagnosis, some remain without a known genetic anomaly. Methods: We performed exome sequencing for four individuals with TCS but who were negative for pathogenic variants in the known causative genes. The effect of the pathogenic variants was investigated in zebrafish. Results: We identified three novel pathogenic variants in POLR1B. Knockdown of polr1b in zebrafish induced an abnormal craniofacial phenotype mimicking TCS that was associated with altered ribosomal gene expression, massive p53-associated cellular apoptosis in the neuroepithelium, and reduced number of NCC derivatives. Conclusion: Pathogenic variants in the RNA polymerase I subunit POLR1B might induce massive p53-dependent apoptosis in a restricted neuroepithelium area, altering NCC migration and causing cranioskeletal malformations. We identify POLR1B as a new causative gene responsible for a novel TCS syndrome (TCS4) and establish a novel experimental model in zebrafish to study POLR1B-related TCS. © 2019, The Author(s).

Author Keywords
apoptosis;  neural crest cells;  POLR1B;  Treacher Collins–Franceschetti

Document Type: Article
Publication Stage: Article in Press
Source: Scopus

“Median Nerve Compression in the Forearm: A Clinical Diagnosis” (2019) Hand

Median Nerve Compression in the Forearm: A Clinical Diagnosis
(2019) Hand, . 

El-Haj, M.a , Ding, W.b , Sharma, K.a , Novak, C.c , Mackinnon, S.E.a , Patterson, J.M.M.d

a Washington University School of Medicine, St. Louis, MO, United States
b Shanghai Ninth People’s Hospital, China
c University of TorontoON, Canada
d University of North Carolina School of Medicine, Chapel Hill, United States

Abstract
Background: Median nerve entrapment in the forearm (MNEF) without motor paralysis is a challenging diagnosis. This retrospective study evaluated the clinical presentation, diagnostic studies, and outcomes following surgical decompression of MNEF. Methods: The study reviewed 147 patient medical charts following MNEF surgical decompression. With exclusion of patients with combined nerve entrapments (radial and ulnar), polyneuropathy, neurotmetic nerve injury, or median nerve motor palsy, the study sample included 27 patients. Data collected include: clinical presentation and pain, strength, provocative testing, functional outcomes, and Disabilities of the Arm, Shoulder and Hand (DASH) scores. Results: The study included 27 patients (mean follow-up = 7 months), and 13 patients had previous carpal tunnel release (CTR). Clinical presentation included pain (n = 27) (forearm, n = 22; median nerve innervated digits, n = 21; and palm, n = 21) and positive clinical tests (forearm scratch collapse test, n = 27; pain with compression over the flexor digitorum superficialis arch/pronator, n = 24; Tinel sign, n = 11). Positive electrodiagnostic studies were found for MNEF (n = 2) and carpal tunnel syndrome (n = 11). Primary CTR was performed in 10 patients and revision CTR in 7 patients. Postoperatively, there were significant (P <.05) improvements in strength, pain, quality of life, and DASH scores. Conclusions: The MNEF without motor paralysis is a clinical diagnosis supported by pain drawings, pain quality, and provocative tests. Patients with persistent forearm pain and median nerve symptoms (especially after CTR) should be evaluated for MNEF. Surgical decompression provides satisfactory outcomes. © The Author(s) 2019.

Author Keywords
electrodiagnostic studies;  follow-up studies;  median nerve compression;  nerve compression syndromes;  pronator syndrome;  recurrent carpal tunnel syndrome;  surgical decompression

Document Type: Article
Publication Stage: Article in Press
Source: Scopus

“Objective and Subjective Social Isolation and Psychiatric Disorders Among African Americans” (2019) Clinical Social Work Journal

Objective and Subjective Social Isolation and Psychiatric Disorders Among African Americans
(2019) Clinical Social Work Journal, . 

Nguyen, A.W.a , Taylor, R.J.b , Taylor, H.O.c , Chatters, L.M.b

a Jack, Joseph and Morton Mandel School of Applied Social Sciences, Case Western Reserve University, 11235 Bellflower Rd, Cleveland, OH 44106, United States
b University of Michigan, Ann Arbor, United States
c Washington University in St. Louis, St. Louis, United States

Abstract
Social isolation is a major problem in the United States that has adverse impacts on health and well-being. However, few studies investigate social isolation among African Americans or the impact of social isolation on psychiatric disorders. This study addresses this gap by investigating the impact of objective (absence of contact with others) and subjective (lacking feelings of closeness to others) social isolation on psychiatric disorders among African Americans. The sample includes 3570 African Americans from the National Survey of American Life. Regression models were used to test the impact of objective and subjective isolation on 12-month MDD, any 12-month DSM disorder and number of 12-month DSM disorders. Analyses indicated that subjective isolation from family only, friends only, and both groups were associated with greater odds of meeting criteria for 12-month MDD, any 12-month disorder and number of 12-month DSM disorders. However, objective isolation was unrelated to either measure of psychiatric disorder. Study findings indicate that affective characteristics of social isolation (feelings of closeness with family and friends) are more significant for psychiatric disorders than are objective features (social contact). Our discussion notes that the connections between subjective and objective social isolation and psychiatric disorders are complex and potentially reciprocally associated with one another. Clinical practice should focus on both possible associations. © 2019, Springer Science+Business Media, LLC, part of Springer Nature.

Author Keywords
African American mental health;  Social disconnectedness;  Social networks;  Social relationships

Document Type: Article
Publication Stage: Article in Press
Source: Scopus

“Detecting associations between intact connectomes and clinical covariates using recursive partitioning object-oriented data analysis” (2019) Statistics in Medicine

Detecting associations between intact connectomes and clinical covariates using recursive partitioning object-oriented data analysis
(2019) Statistics in Medicine, 38 (29), pp. 5486-5496. 

Yang, D.a , Deych, E.a , Shands, B.a , Campbell, M.C.b , Perlmutter, J.S.b , Petersen, S.b , Schlaggar, B.L.c , Shannon, W.a b

a BioRankings, St. Louis, MO, United States
b Washington University School of Medicine, St. Louis, MO, United States
c Kennedy Krieger Institute, Johns Hopkins University, Baltimore, MD, United States

Abstract
Many neuroscientists are interested in how connectomes (graphical representations of functional connectivity between areas of the brain) change in relation to covariates. In statistics, changes like this are analyzed using regression, where the outcomes or dependent variables are regressed onto the covariates. However, when the outcome is a complex object, such as connectome graphs, classical regression models cannot be used. The regression approach developed here to work with complex graph outcomes combines recursive partitioning with the Gibbs distribution. We will only discuss the application to connectomes, but the method is generally applicable to any graphical outcome. The method, called Gibbs-RPart, partitions the covariate space into a set of nonoverlapping regions such that the connectomes within regions are more similar than they are to the connectomes in other regions. This paper extends the object-oriented data analysis paradigm for graph-valued data based on the Gibbs distribution, which we have applied previously to hypothesis testing to compare populations of connectomes from distinct groups (see the work of La Rosa et al). © 2019 John Wiley & Sons, Ltd.

Author Keywords
connectome;  object-oriented data analysis;  recursive partitioning;  regression

Document Type: Article
Publication Stage: Final
Source: Scopus

“Nerve transfers in the upper extremity following cervical spinal cord injury. Part 2: Preliminary results of a prospective clinical trial” (2019) Journal of Neurosurgery: Spine

Nerve transfers in the upper extremity following cervical spinal cord injury. Part 2: Preliminary results of a prospective clinical trial
(2019) Journal of Neurosurgery: Spine, 31 (5), pp. 641-653. Cited 1 time.

Khalifeh, J.M.a , Dibble, C.F.a , Van Voorhis, A.b , Doering, M.c , Boyer, M.I.d , Mahan, M.A.e , Wilson, T.J.f , Midha, R.g , Yang, L.J.S.h , Ray, W.Z.a

a Department of Neurological Surgery, Program in Occupational Therapy, United States
b Milliken Hand Rehabilitation Center, Program in Occupational Therapy, United States
c Bernard Becker Medical Library, Washington University School of Medicine, St. Louis, MO, United States
d Department of Orthopedic Surgery, Washington University School of Medicine, St. Louis, MO, United States
e Department of Neurosurgery, University of Utah School of Medicine, Salt Lake City, UT, United States
f Department of Neurosurgery, Stanford University School of Medicine, Palo Alto, CA, United States
g Department of Clinical Neurosciences, University of Calgary, Alberta, Canada
h Department of Neurological Surgery, University of Michigan, School of Medicine, Ann Arbor, MI, United States

Abstract
OBJECTIVE Patients with cervical spinal cord injury (SCI)/tetraplegia consistently rank restoring arm and hand function as their top functional priority to improve quality of life. Motor nerve transfers traditionally used to treat peripheral nerve injuries are increasingly used to treat patients with cervical SCIs. In this article, the authors present early results of a prospective clinical trial using nerve transfers to restore upper-extremity function in tetraplegia. METHODS Participants with American Spinal Injury Association (ASIA) grade A.C cervical SCI/tetraplegia were prospectively enrolled at a single institution, and nerve transfer(s) was performed to improve upper-extremity function. Functional recovery and strength outcomes were independently assessed and prospectively tracked. RESULTS Seventeen participants (94.1% males) with a median age of 28.4 years (range 18.2.76.3 years) who underwent nerve transfers at a median of 18.2 months (range 5.2.130.8 months) after injury were included in the analysis. Preoperative SCI levels ranged from C2 to C7, most commonly at C4 (35.3%). The median postoperative follow-up duration was 24.9 months (range 12.0.29.1 months). Patients who underwent transfers to median nerve motor branches and completed 18-and 24-month follow-ups achieved finger flexion strength Medical Research Council (MRC) grade. 3/5 in 4 of 15 (26.7%) and 3 of 12 (25.0%) treated upper limbs, respectively. Similarly, patients achieved MRC grade. 3/5 wrist flexion strength in 5 of 15 (33.3%) and 3 of 12 (25.0%) upper limbs. Among patients who underwent transfers to the posterior interosseous nerve (PIN) for wrist/finger extension, MRC grade. 3/5 strength was demonstrated in 5 of 9 (55.6%) and 4 of 7 (57.1%) upper limbs 18 and 24 months postoperatively, respectively. Similarly, grade. 3/5 strength was demonstrated in 5 of 9 (55.6%) and 4 of 7 (57.1%) cases for thumb extension. No meaningful donor site deficits were observed. Patients reported significant postoperative improvements from baseline on upper-extremity.specific selfreported outcome measures. CONCLUSIONS Motor nerve transfers are a promising treatment option to restore upper-extremity function after SCI. In the authors f experience, nerve transfers for the reinnervation of hand and finger flexors showed variable functional recovery; however, transfers for the reinnervation of arm, hand, and finger extensors showed a more consistent and meaningful return of strength and function © AANS 2019, except where prohibited by US copyright law.

Author Keywords
Cervical spinal cord;  clinical trial;  Disability;  Hand function;  Nerve transfer;  Spinal cord injury;  Tetraplegia;  Upper extremity

Document Type: Article
Publication Stage: Final
Source: Scopus

“Predicting risk for Alcohol Use Disorder using longitudinal data with multimodal biomarkers and family history: a machine learning study” (2019) Molecular Psychiatry

Predicting risk for Alcohol Use Disorder using longitudinal data with multimodal biomarkers and family history: a machine learning study
(2019) Molecular Psychiatry, . 

Kinreich, S.a , Meyers, J.L.a , Maron-Katz, A.b , Kamarajan, C.a , Pandey, A.K.a , Chorlian, D.B.a , Zhang, J.a , Pandey, G.a , Subbie-Saenz de Viteri, S.a , Pitti, D.a , Anokhin, A.P.c , Bauer, L.d , Hesselbrock, V.d , Schuckit, M.A.e , Edenberg, H.J.f g , Porjesz, B.a

a Department of Psychiatry, State University of New York Downstate Medical Center, Brooklyn, NY, United States
b Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, United States
c Department of Psychiatry, Washington University School of Medicine, St Louis, MO, United States
d Department of Psychiatry, University of Connecticut School of Medicine, Farmington, CT, United States
e Department of Psychiatry, University of California, San Diego School of Medicine, La Jolla, CA, United States
f Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, United States
g Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN, United States

Abstract
Predictive models have succeeded in distinguishing between individuals with Alcohol use Disorder (AUD) and controls. However, predictive models identifying who is prone to develop AUD and the biomarkers indicating a predisposition to AUD are still unclear. Our sample (n = 656) included offspring and non-offspring of European American (EA) and African American (AA) ancestry from the Collaborative Study of the Genetics of Alcoholism (COGA) who were recruited as early as age 12 and were unaffected at first assessment and reassessed years later as AUD (DSM-5) (n = 328) or unaffected (n = 328). Machine learning analysis was performed for 220 EEG measures, 149 alcohol-related single nucleotide polymorphisms (SNPs) from a recent large Genome-wide Association Study (GWAS) of alcohol use/misuse and two family history (mother DSM-5 AUD and father DSM-5 AUD) features using supervised, Linear Support Vector Machine (SVM) classifier to test which features assessed before developing AUD predict those who go on to develop AUD. Age, gender, and ancestry stratified analyses were performed. Results indicate significant and higher accuracy rates for the AA compared with the EA prediction models and a higher model accuracy trend among females compared with males for both ancestries. Combined EEG and SNP features model outperformed models based on only EEG features or only SNP features for both EA and AA samples. This multidimensional superiority was confirmed in a follow-up analysis in the AA age groups (12–15, 16–19, 20–30) and EA age group (16–19). In both ancestry samples, the youngest age group achieved higher accuracy score than the two other older age groups. Maternal AUD increased the model’s accuracy in both ancestries’ samples. Several discriminative EEG measures and SNPs features were identified, including lower posterior gamma, higher slow wave connectivity (delta, theta, alpha), higher frontal gamma ratio, higher beta correlation in the parietal area, and 5 SNPs: rs4780836, rs2605140, rs11690265, rs692854, and rs13380649. Results highlight the significance of sampling uniformity followed by stratified (e.g., ancestry, gender, developmental period) analysis, and wider selection of features, to generate better prediction scores allowing a more accurate estimation of AUD development. © 2019, The Author(s), under exclusive licence to Springer Nature Limited.

Document Type: Article
Publication Stage: Article in Press
Source: Scopus

“Home Environment, Living Alone, and Trajectories of Cognitive Function Among Older Adults With Functional Limitations” (2019) Environment and Behavior

Home Environment, Living Alone, and Trajectories of Cognitive Function Among Older Adults With Functional Limitations
(2019) Environment and Behavior, . 

Park, S.a , Kim, B.b , Amano, T.a , Chen, Q.a

a Washington University in St. LouisMO, United States
b University of New Hampshire, Durham, United States

Abstract
This study aimed to investigate the effects of Person-Environment Fit on trajectories of cognitive function. Data came from the Health Retirement Study (1998-2010), focusing on those aged 65 and above who had at least one limitation in activities of daily living. Using longitudinal mixed-effect modeling, we analyzed the effects of living in supportive home environments on trajectories of cognitive function over time. Disabled older individuals living alone were likely to experience a decline in cognitive function over time. However, the detrimental effects of living alone were moderated when the home was equipped with supportive features and accessibility. The findings reveal the importance of home modifications for socially and physically vulnerable elders. © The Author(s) 2019.

Author Keywords
cognitive function;  disability;  home environment;  living alone;  the person-environment fit

Document Type: Article
Publication Stage: Article in Press
Source: Scopus

“Nerve transfers in the upper extremity following cervical spinal cord injury. Part 1: Systematic review of the literature” (2019) Journal of Neurosurgery: Spine

Nerve transfers in the upper extremity following cervical spinal cord injury. Part 1: Systematic review of the literature
(2019) Journal of Neurosurgery: Spine, 31 (5), pp. 629-640. Cited 1 time.

Khalifeh, J.M.a , Dibble, C.F.a , Van Voorhis, A.b , Doering, M.c , Boyer, M.I.d , Mahan, M.A.e , Wilson, T.J.f , Midha, R.g , Yang, L.J.S.h , Ray, W.Z.a

a Department of Neurological Surgery, Washington University School of Medicine, St. Louis, MO, United States
b Milliken Hand Rehabilitation Center, Program in Occupational Therapy, Washington University School of Medicine, St. Louis, MO, United States
c Bernard Becker Medical Library, Washington University School of Medicine, St. Louis, MO, United States
d Department of Orthopedic Surgery, Washington University School of Medicine, St. Louis, MO, United States
e Department of Neurosurgery, University of Utah School of Medicine, Salt Lake City, UT, United States
f Department of Neurosurgery, Stanford University School of Medicine, Palo Alto, CA, United States
g Department of Clinical Neurosciences, University of Calgary, Alberta, Canada
h Department of Neurological Surgery, University of Michigan School of Medicine, Ann Arbor, MI, United States

Abstract
OBJECTIVE Patients with cervical spinal cord injury (SCI)/tetraplegia consistently rank restoring arm and hand function as their top functional priority to improve quality of life. Motor nerve transfers traditionally used to treat peripheral nerve injuries are increasingly being used to treat patients with cervical SCIs. In this study, the authors performed a systematic review summarizing the published literature on nerve transfers to restore upper-extremity function in tetraplegia. METHODS A systematic literature search was conducted using Ovid MEDLINE 1946–, Embase 1947–, Scopus 1960–, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and clinicaltrials.gov to identify relevant literature published through January 2019. The authors included studies that provided original patient-level data and extracted information on clinical characteristics, operative details, and strength outcomes after nerve transfer procedures. Critical review and synthesis of the articles were performed. RESULTS Twenty-two unique studies, reporting on 158 nerve transfers in 118 upper limbs of 92 patients (87 males, 94.6%) were included in the systematic review. The mean duration from SCI to nerve transfer surgery was 18.7 months (range 4 months–13 years) and mean postoperative follow-up duration was 19.5 months (range 1 month–4 years). The main goals of reinnervation were the restoration of thumb and finger flexion, elbow extension, and wrist and finger extension. Significant heterogeneity in transfer strategy and postoperative outcomes were noted among the reports. All but one case report demonstrated recovery of at least Medical Research Council grade 3/5 strength in recipient muscle groups; however, there was greater variation in the results of larger case series. The best, most consistent outcomes were demonstrated for restoration of wrist/finger extension and elbow extension. CONCLUSIONS Motor nerve transfers are a promising treatment option to restore upper-extremity function after SCI. Flexor reinnervation strategies show variable treatment effect sizes; however, extensor reinnervation may provide more consistent, meaningful recovery. Despite numerous published case reports describing good patient outcomes with nerve transfers, there remains a paucity in the literature regarding optimal timing and long-term clinical outcomes with these procedures. © AANS 2019.

Author Keywords
Cervical spinal cord;  Disability;  Hand function;  Nerve transfer;  Spinal cord injury;  Systematic review;  Tetraplegia;  Upper extremity

Document Type: Review
Publication Stage: Final
Source: Scopus

“The cell nucleus as sensor of environmental pollution: Amyloid, neurodegeneration and aging” (2019) Biopolymers and Cell

The cell nucleus as sensor of environmental pollution: Amyloid, neurodegeneration and aging
(2019) Biopolymers and Cell, 35 (3), pp. 195-196. 

Piechulek, A.a , Berwanger, L.a , Scharf, A.b , von Mikecz, A.a

a IUF – Leibniz Research Institute of Environmental Medicine, Heinrich-Heine-University Duesseldorf, Duesseldorf, Germany
b Washington University, St. Louis, United States

Document Type: Note
Publication Stage: Final
Source: Scopus
Access Type: Open Access

“Tracking intentionalism and the phenomenology of mental effort” (2019) Synthese

Tracking intentionalism and the phenomenology of mental effort
(2019) Synthese, . 

Doulatova, M.

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

Abstract
Most of us are familiar with the phenomenology of mental effort accompanying cognitively demanding tasks, like focusing on the next chess move or performing lengthy mental arithmetic. In this paper, I argue that phenomenology of mental effort poses a novel counterexample to tracking intentionalism, the view that phenomenal consciousness is a matter of tracking features of one’s environment in a certain way. I argue that an increase in the phenomenology of mental effort does not accompany a change in any of the following candidate representational contents: (a) representation of externally presented features, e.g. brightness, contrast, and so on (b) representation of task difficulty, (c) representation of the possibility of error, (d) representation of trying to achieve some state of affairs, (e) representation of bodily changes like muscle tension, or (f) representation of change in cognitive resource availability and lost opportunity cost. While tracking intentionalism about some phenomenal experiences like pains might obtain, it does not seem to obtain for all phenomenal experiences. This puts the intentionalist into an uncomfortable position of trying to explain why some phenomenal experiences have representational content and not others. Since many believe that tracking intentionalism or something like it provides the best chance of naturalizing consciousness, these arguments deserve detailed consideration. © 2019, Springer Nature B.V.

Author Keywords
Attention;  Mental effort;  Qualia;  Reductionist theories of consciousness;  Tracking intentionalism

Document Type: Article
Publication Stage: Article in Press
Source: Scopus

“Understanding the experience of psychopathology after intimate partner violence: The role of personality” (2019) PeerJ

Understanding the experience of psychopathology after intimate partner violence: The role of personality
(2019) PeerJ, 2019 (3), art. no. e6647, . 

Moreira, P.A.S.a b , Pinto, M.b c , Cloninger, C.R.d , Rodrigues, D.b e , Silva, C.F.D.f g

a Instituto de Psicologia e de Ciências da Educacaõ, Universidade Lusiáda Norte (Porto), Porto, Portugal
b Centro de Investigacaõ em Psicologia para O Desenvolvimento, CIPD, Porto, Portugal
c Centro de Acolhimento Temporário ÂNcora, Associacaõ para O Desenvolvimento de Rebordosa, Rebordosa, Portugal
d United States of America, School of Medicine, Washington University in St. Louis, St. Louis, MO, United States
e Estabelecimento Prisional de Santa Cruz Do Bispo Masculino, Direcaõ Geral de Reinsercaõ e Servificos Prisionais, Matosinhos, Portugal
f Departamento de Educaficaõ e Psicologia, Universidade de Aveiro, Aveiro, Portugal
g Center for Health Technology and Services Research, CINTESIS, Porto, Portugal

Abstract
Objective(s). To fully understand the dynamics of Intimate Partner Violence (IPV) it is necessary to understand the role of personality. The current understanding of which personality characteristics are associated with IPV victimization is, however, far from comprehensive. Given this gap in the literature, our objective was to examine the associations between the dimensions of the psychobiological model of personality and psychopathological symptoms in women who had experienced IPV. Methods. Using a case-control design, a group of women who had experienced IPV and who were living in shelters (n D 50) were compared to a group of control women who had not experienced IPV (n D 50). All women completed the Temperament and Character Inventory Revised and the Brief Symptom Inventory. Results. Victims of IPV showed significantly higher levels of Harm Avoidance and Self-Transcendence, and lower levels of Reward Dependence and Self-Directedness, than the non-IPV control group. Victims of IPV also reported elevated levels of psychopathological symptoms. Personality dimensions showed a broadly consistent pattern of associations across different psychopathological symptoms. A regression analysis indicated that Novelty Seeking was negatively associated with psychopathological symptoms in victims of IPV, but not significantly associated in non-victims. Conclusions. The study highlights the important role of Harm Avoidance and Self-Directedness for understanding psychopathological symptoms. Novelty Seeking appears to play an important role in the expression of individuals’ experiences of IPV. These results have important implications for research and practice, particularly the development and implementation of interventions. © 2019 PeerJ Inc.. All rights reserved.

Author Keywords
Character;  Domestic violence;  Intimate partner violence;  Personality;  Psychopathological symptoms;  Temperament;  Victims;  Women

Document Type: Article
Publication Stage: Final
Source: Scopus
Access Type: Open Access

“Prevalence of Ototoxicity Following Hematopoietic Stem Cell Transplantation in Pediatric Patients” (2019) Biology of Blood and Marrow Transplantation

Prevalence of Ototoxicity Following Hematopoietic Stem Cell Transplantation in Pediatric Patients
(2019) Biology of Blood and Marrow Transplantation, . 

Gertson, K.a , Hayashi, S.S.b , Trinkaus, K.c , Wan, F.c , Hayashi, R.J.d

a Program in Audiology and Communication Sciences, Washington University School of Medicine, St Louis, MO, United States
b Audiology Division, St Louis Children’s Hospital, St Louis, MO, United States
c Biostatistics Shared Resource, Siteman Cancer Center, Washington University School of Medicine, St Louis, MO, United States
d Siteman Cancer Center, Washington University School of Medicine, St. Louis Children’s Hospital, St Louis, MO, United States

Abstract
The use of hematopoietic stem cell transplantation (HSCT) is increasing for a variety of diseases. Ototoxicity from this procedure has not been extensively studied. A retrospective chart review examined 275 patients from this institution who underwent HSCT between January 1, 2007, and April 30, 2017. Data extracted included therapy before HSCT and the subsequent course of transplantation. Evaluable patients had complete medical records and interpretable audiograms available. Ototoxicity constituted significant threshold changes from baseline or changes in International Society of Pediatric Oncology/Boston Ototoxicity Grading Scale (SIOP) grade comparing audiogram results just before HSCT with those following the transplantation procedure. A total of 147 patients were evaluable. Ototoxicity was observed in 10.2% of the patients. Higher SIOP grade before HSCT was significantly associated with a higher risk of post-transplantation ototoxicity (P <.01). Previous cisplatin treatment (P <.0001), but not carboplatin or radiation treatment, was also associated with ototoxicity. Patients with a solid tumor or brain tumor (P <.0001) and those who received an autologous transplant (P =.0002) were also at increased risk. No post-transplantation event was significantly associated with ototoxicity. Ototoxicity affects a significant percentage of patients undergoing HSCT, and careful monitoring is needed to identify patients impacted by this procedure. © 2019 American Society for Transplantation and Cellular Therapy

Author Keywords
Ototoxicity;  Pediatric;  Stem cell transplantation

Document Type: Article
Publication Stage: Article in Press
Source: Scopus

“Antimicrobial therapy utilization in neonates with hypoxic-ischemic encephalopathy (HIE): a report from the Children’s Hospital Neonatal Database (CHND)” (2019) Journal of Perinatology

Antimicrobial therapy utilization in neonates with hypoxic-ischemic encephalopathy (HIE): a report from the Children’s Hospital Neonatal Database (CHND)
(2019) Journal of Perinatology, . 

Rao, R.a , Lee, K.-S.b , Zaniletti, I.c , Yanowitz, T.D.d , DiGeronimo, R.e , Dizon, M.L.V.f , Hamrick, S.E.g , Natarajan, G.h , Peeples, E.S.i , Murthy, K.f , Mathur, A.M.j , Massaro, A.k

a Pediatrics, Washington University School of Medicine, St. Louis, MO, United States
b Pediatrics, Hospital for Sick Children, Toronto, ON, Canada
c Children’s Hospitals Association, Columbia, MO, United States
d Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States
e Pediatrics/Neonatology, Seattle Children’s Hospital/University of Washington, Seattle, WA, United States
f Pediatrics/Neonatology, Northwestern University, Chicago, IL, United States
g Pediatrics, Emory University, Atlanta, GA, United States
h Children’s Hospital of Michigan, Detroit, MI, United States
i Pediatrics, University of Nebraska Medical Center, Omaha, NE, United States
j Pediatrics, St Louis University, St louis, MO, United States
k Neonatology, Children’s National Health Systems, Washington, DC, United States

Abstract
Objective(s): Quantify antimicrobial therapy (AMT) use in newborns with hypoxic-ischemic encephalopathy treated with therapeutic hypothermia (HIE/TH). Study design: Newborns with HIE/TH were identified from the Children’s Hospital Neonatal Database (CHND). Early infection (onset ≤7 days of life) was defined as “confirmed” (culture proven) or “suspected infection” (culture negative but treated) and compared with a “no infection” group. Results: 1501/1534 (97.8%) neonates received AMT. 36 (2.3%) had confirmed, 255 (16.6%) suspected, and 1243 (81.0%) had no infection. The median (IQR) AMT duration was 13 (8–21), 8 (7–10), and 3 (3–7) days for the three groups, respectively (p < 0.001). AMT duration of use varied significantly across centers, adjusted for covariates (OR 1.88, 95% CI: 1.43–2.46). Conclusion(s): Incidence of early confirmed infection in neonates with HIE/TH (23/1000) is significantly higher than reported rates of early onset sepsis in term and near term infants (0.5–1.0/1000 live births). Antimicrobial-stewardship opportunities exist in infants with negative cultures. © 2019, The Author(s), under exclusive licence to Springer Nature America, Inc.

Document Type: Article
Publication Stage: Article in Press
Source: Scopus

“The characteristics of cognitive neuroscience tests in a schizophrenia cognition clinical trial: Psychometric properties and correlations with standard measures” (2019) Schizophrenia Research: Cognition

The characteristics of cognitive neuroscience tests in a schizophrenia cognition clinical trial: Psychometric properties and correlations with standard measures
(2019) Schizophrenia Research: Cognition, art. no. 100161, . 

Kraus, M.S.a , Gold, J.M.b , Barch, D.M.c , Walker, T.M.a , Chun, C.A.d , Buchanan, R.W.b , Csernansky, J.G.e , Goff, D.C.f , Green, M.F.g h , Jarskog, L.F.i , Javitt, D.C.j , Kimhy, D.k , Lieberman, J.A.l , McEvoy, J.P.a , Mesholam-Gately, R.I.m , Seidman, L.J.f m , Ball, M.P.b , Kern, R.S.g h , McMahon, R.P.b , Robinson, J.j , Marder, S.R.g h , Keefe, R.S.E.a

a Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC, United States
b Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, United States
c Department of Psychiatry, Washington University in St. Louis School of Medicine, St. Louis, MO, United States
d Temple University, Philadelphia, PA, United States
e Department of Psychiatry, Northwestern Feinberg School of Medicine, Chicago, IL, United States
f Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, United States
g UCLA Semel Institute for Neuroscience and Human Behavior, United States
h VA VISN 22 Mental Illness Research, Education, and Clinical Center, Los Angeles, CA, United States
i North Carolina Psychiatric Research Center, Department of Psychiatry, University of North Carolina at Chapel Hill, United States
j Department of Psychiatry, Nathan Kline Institute for Psychiatric Research, New York University School of Medicine, New York, NY, United States
k Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, United States
l Department of Psychiatry, New York State Psychiatric Institute and College of Physicians and Surgeons, Columbia University, United States
m Department of Psychiatry, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States

Abstract
In comparison to batteries of standard neuropsychological tests, cognitive neuroscience tests may offer a more specific assessment of discrete neurobiological processes that may be aberrant in schizophrenia. However, more information regarding psychometric properties and correlations with standard neuropsychological tests and functional measures is warranted to establish their validity as treatment outcome measures. The N-back and AX-Continuous Performance Task (AX-CPT) are two promising cognitive neuroscience tests designed to measure specific components of working memory and contextual processing respectively. In the current study, we report the psychometric properties of multiple outcome measures from these two tests as well as their correlations with standard neuropsychological measures and functional capacity measures. The results suggest that while the AX-CPT and N-back display favorable psychometric properties, they do not exhibit greater sensitivity or specificity with functional measures than standard neurocognitive tests. © 2019

Document Type: Article
Publication Stage: Article in Press
Source: Scopus
Access Type: Open Access

“A management algorithm for patients with intracranial pressure monitoring: the Seattle International Severe Traumatic Brain Injury Consensus Conference (SIBICC)” (2019) Intensive Care Medicine

A management algorithm for patients with intracranial pressure monitoring: the Seattle International Severe Traumatic Brain Injury Consensus Conference (SIBICC)
(2019) Intensive Care Medicine, . Cited 2 times.

Hawryluk, G.W.J.a , Aguilera, S.b c , Buki, A.d e , Bulger, E.f , Citerio, G.g h , Cooper, D.J.i j , Arrastia, R.D.k , Diringer, M.l m , Figaji, A.n , Gao, G.o , Geocadin, R.p , Ghajar, J.q , Harris, O.r , Hoffer, A.s , Hutchinson, P.t , Joseph, M.u , Kitagawa, R.v , Manley, G.w , Mayer, S.x , Menon, D.K.y , Meyfroidt, G.z , Michael, D.B.aa , Oddo, M.ab , Okonkwo, D.ac , Patel, M.ad , Robertson, C.ae , Rosenfeld, J.V.af ag , Rubiano, A.M.ah ai , Sahuquillo, J.aj , Servadei, F.ak , Shutter, L.al , Stein, D.am , Stocchetti, N.an ao , Taccone, F.S.ap , Timmons, S.aq , Tsai, E.ar , Ullman, J.S.as , Vespa, P.at au av aw , Videtta, W.ax , Wright, D.W.ay , Zammit, C.az , Chesnut, R.M.ba bb bc bd

a Section of Neurosurgery, University of Manitoba, GB1, 820 Sherbrook Street, Winnipeg, MB R3A 1R9, Canada
b Almirante Nef Naval Hospital, Valparaiso University, Viña Del Mar, Chile
c Valparaiso University, Valparaiso, Chile
d Department of Neurosurgery, Medical School and Szentágothai Research Centre, Ifjúság Útja 20, Pécs, 7624, Hungary
e University of Pécs, Pécs, Hungary
f Department of Surgery, Harborview Medical Center, University of Washington, 325 Ninth Ave, Seattle, WA 98104-2499, United States
g School of Medicine and Surgery, University of Milan-Bicocca, Milan, Italy
h Anaesthesia and Intensive Care, San Gerardo and Desio Hospitals, ASST-Monza, Monza, Italy
i Intensive Care Medicine, Australian and New Zealand Intensive Care Research Centre, Monash University, Melbourne, Australia
j Department of Intensive Care and Hyperbaric Medicine, The Alfred Hospital, Melbourne, VIC, Australia
k Department of Neurology, Penn Presbyterian Medical Center, University of Pennsylvania Perelman School of Medicine, 51 North 39th Street, Philadelphia, PA 19104, United States
l Department of Neurology, Washington University School of Medicine, St. Louis, United States
m Department of Neurology, Barnes-Jewish Hospital, 1 Barnes Jewish Hospital Plaza Suite 10400, St. Louis, MO 63110, United States
n Division of Neurosurgery and Neuroscience Institute, Groote Schuur Hospital¸University of Cape Town, H53 Old Main Building, Main Road, Observatory, 7925, South Africa
o Department of Neurosurgery, Renji Hospital, Shanghai Institute of Head Trauma, Shanghai Jiaotong University School of Medicine, 1630 Dongfang Road, Shanghai, 200127, China
p Department of Neurology, Johns Hopkins University School of Medicine, 600 N. Wolfe Street, Phipps 455, Baltimore, MD 21287, United States
q Department of Neurosurgery, Stanford Neuroscience Health Center, 213 Quarry Rd 4th Fl, MC 5958, Palo Alto, CA 94304, United States
r Department of Neurosurgery, 300 Pasteur Drive, Room R205, Edward’s Building, MC: 5327, Stanford, CA 94305, United States
s Department of Neurological Surgery, School of Medicine, Case Western Reserve University, 11100 Euclid Avenue, 5042, Cleveland, OH 44106, United States
t Division of Neurosurgery, Department of Clinical Neurosciences, Addenbrooke’s Hospital, University of Cambridge and Cambridge Biomedical Campus, Cambridge, CB20QQ, United Kingdom
u Department of Neurological Sciences, Christian Medical College, Ida Scudder Road, Vellore, Tamil Nadu, India
v Vivian L Smith Department of Neurosurgery, McGovern Medical School at UTHealth, 6400 Fannin St, Suite 2800, Houston, TX 77030, United States
w Department of Neurosurgery, San Francisco General Hospital and Trauma Center, University of California San Francisco, 1001 Potrero Ave., Bldg 1, Room 101, San Francisco, CA 94110, United States
x Department of Neurology, Henry Ford Hospital, 2799 W Grand Blvd, Neurology, K-11, Detroit, MI 48202, United States
y Division of Anaesthesia, Addenbrooke’s Hospital, University of Cambridge and Addenbrooke’s Hospital, Hills Road, Box 93, Cambridge, CB2 0QQ, United Kingdom
z Department and Laboratory of Intensive Care Medicine, University Hospitals Leuven and KU Leuven, Herestraat 49, Box 7003 63, Leuven, 3000, Belgium
aa Department of Neurosurgery, Beaumont Health, Michigan Head and Spine Institute, Oakland University William Beaumont School of Medicine, Southfield, MI, United States
ab Department of Intensive Care Medicine, Faculty of Biology and Medicine, CHUV-Lausanne University Hospital, University of Lausanne, Lausanne, Switzerland
ac Department of Neurosurgery, University of Pittsburgh Medical Center Presbyterian, Suite B-400 200 Lothrop Street, Pittsburgh, PA 15213, United States
ad Department of Surgery, Vanderbilt University Medical Center, 1211 21st Avenue South, 404 MAB, Nashville, TN 37212, United States
ae Department of Neurosurgery, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, United States
af Department of Neurosurgery, Alfred Hospital, Melbourne, Australia
ag Department of Surgery, Monash University, Melbourne, Australia
ah INUB/MEDITECH Research Group, Neurosciences Institute, El Bosque University, Bogotá, Colombia
ai MEDITECH Foundation, Clinical Research, Calle 7-A # 44-95, Cali, 760036, Colombia
aj Department of Neurosurgery, University Hospital Vall d’Hebron, Barcelona, Spain
ak Department of Neurosurgery, Humanitas University and Research Hospital, Milan, Italy
al Department of Critical Care Medicine, Neurology and Neurosurgery, University of Pittsburgh Medical Center, 3550 Terrace St, Room 646, Pittsburgh, PA 15261, United States
am Department of Surgery, Zuckerberg San Francisco General Hospital and Trauma Center, University of California, 1001 Potrero Ave., Ward 3A, San Francisco, CA 94110, United States
an Department of Physiopathology and Transplantation, Milan University, Milan, Italy
ao Neuroscience Intensive Care Unit, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan, Italy
ap Department of Intensive Care, Hospital Erasme, Université Libre de Bruxelles (ULB), Brussels, Belgium
aq Department of Neurological Surgery, GH 5100 SNEU, Indianapolis, IN 46202, United States
ar Suruchi Bhargava Chair in Spinal Cord and Brain Regeneration Research, The Ottawa Hospital, Department of Surgery, Division of Neurosurgery, University of Ottawa, Civic Campus, 1053 Carling Avenue, Ottawa, ON K1Y 4E9, Canada
as Department of Neurosurgery, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, North Shore University Hospital, 300 Community Drive, 9 Tower, Manhasset, NY, United States
at Gary L. Brinderson Family Chair in Neurocritical Care, UCLA School of Medicine, Los Angeles, United States
au Critical Care Medicine Research, UCLA School of Medicine, Santa Monica, United States
av Neurosurgery and Neurology, UCLA School of Medicine, Santa Monica, United States
aw Neurocritical Care, Ronald Reagan UCLA Medical Center, Santa Monica, United States
ax Intensive Care, Posadas Hospital, Buenos Aires, Argentina
ay Department of Emergency Medicine, Emory University School of Medicine, 49 Jesse Hill Jr Dr, Atlanta, GA 30303, United States
az Department of Emergency Medicine, University of Rochester Medical Center, 265 Crittenden Blvd, Suite 2100, Box 655C, Rochester, NY 14642, United States
ba Department of Neurological Surgery, University of Washington, Mailstop 359766, 325 Ninth Ave, Seattle, WA 98104-2499, United States
bb Department of Orthopaedic Surgery, University of Washington, Mailstop 359766, 325 Ninth Ave, Seattle, WA 98104-2499, United States
bc School of Global Health, University of Washington, Mailstop 359766, 325 Ninth Ave, Seattle, WA 98104-2499, United States
bd Harborview Medical Center, University of Washington, 325 Ninth Ave, Mailstop 359766, Seattle, WA 98104-2499, United States

Abstract
Background: Management algorithms for adult severe traumatic brain injury (sTBI) were omitted in later editions of the Brain Trauma Foundation’s sTBI Management Guidelines, as they were not evidence-based. Methods: We used a Delphi-method-based consensus approach to address management of sTBI patients undergoing intracranial pressure (ICP) monitoring. Forty-two experienced, clinically active sTBI specialists from six continents comprised the panel. Eight surveys iterated queries and comments. An in-person meeting included whole- and small-group discussions and blinded voting. Consensus required 80% agreement. We developed heatmaps based on a traffic-light model where panelists’ decision tendencies were the focus of recommendations. Results: We provide comprehensive algorithms for ICP-monitor-based adult sTBI management. Consensus established 18 interventions as fundamental and ten treatments not to be used. We provide a three-tier algorithm for treating elevated ICP. Treatments within a tier are considered empirically equivalent. Higher tiers involve higher risk therapies. Tiers 1, 2, and 3 include 10, 4, and 3 interventions, respectively. We include inter-tier considerations, and recommendations for critical neuroworsening to assist the recognition and treatment of declining patients. Novel elements include guidance for autoregulation-based ICP treatment based on MAP Challenge results, and two heatmaps to guide (1) ICP-monitor removal and (2) consideration of sedation holidays for neurological examination. Conclusions: Our modern and comprehensive sTBI-management protocol is designed to assist clinicians managing sTBI patients monitored with ICP-monitors alone. Consensus-based (class III evidence), it provides management recommendations based on combined expert opinion. It reflects neither a standard-of-care nor a substitute for thoughtful individualized management. © 2019, The Author(s).

Author Keywords
Algorithm;  Brain injury;  Consensus;  Head trauma;  Intracranial pressure;  Protocol;  Seattle;  SIBICC;  Tiers

Document Type: Conference Paper
Publication Stage: Article in Press
Source: Scopus
Access Type: Open Access

“Comparison of 1-field, 2-fields, and 3-fields fundus photography for detection and grading of diabetic retinopathy” (2019) Journal of Diabetes and its Complications

Comparison of 1-field, 2-fields, and 3-fields fundus photography for detection and grading of diabetic retinopathy
(2019) Journal of Diabetes and its Complications, art. no. 107441, . 

Lee, J.C.a , Nguyen, L.b , Hynan, L.S.c , Blomquist, P.H.a

a Department of Ophthalmology, The University of Texas Southwestern Medical Center, Dallas, TX, United States
b Department of Ophthalmology and Visual Sciences, Washington University, St. Louis, MO, United States
c Departments of Population and Data Sciences (Biostatistics), and Psychiatry, The University of Texas Southwestern Medical Center, Dallas, TX, United States

Abstract
Aim: To evaluate the sensitivity and specificity of 1-, 2-, and 3-fields, nonmydriatic (NM), 45° color photography compared with mydriatic ophthalmoscopy for detection of diabetic retinopathy (DR). Methods: Masked, comparative case series was performed utilizing a group of 128 diabetic patients (256 eyes) with various stages of DR who underwent both 3-fields NM color photography and ophthalmologic examination. In a blinded manner, the same optometrist who read the original 3-fields images for a patient read the 1- and 2-fields photographs on separate dates later. Results: The sensitivity and specificity of digital retinal photography compared with dilated ophthalmoscopy were, respectively: 88% and 76% for 1-field; 94% and 69% for 2-fields; and 100% and 79% for 3-fields. The proportion of agreement between fundus photography reading and exam DR diagnosis were 58% for 1-field, 58% for 2-fields, and 77% for 3-fields. Kappa and Cramer’s V statistics for 1-, 2-, and 3-fields were 0.55 and 0.60, 0.52 and 0.57, and 0.72 and 0.74, respectively. Three-fields measurement of DR was most similar to the dilated ophthalmological exam overall and across all DR severity levels. Conclusions: Compared to 1- and 2-fields fundus photography, 3-fields is superior for detecting vision-threatening DR. One- and 2-fields have reasonable sensitivity for DR screening. © 2019

Author Keywords
Diabetic retinopathy;  Fundus photography;  Screening

Document Type: Article
Publication Stage: Article in Press
Source: Scopus