Medicine and Health Sciences Commons^™

Applying Multiple Data Collection Tools To Quantify Human Papillomavirus Vaccine Communication On Twitter., Philip M. Massey, Amy Leader, Elad Yom-Tov, Alexandra Budenz, Kara Fisher, Ann C. Klassen

Department of Medical Oncology Faculty Papers

BACKGROUND: Human papillomavirus (HPV) is the most common sexually transmitted infection in the United States. There are several vaccines that protect against strains of HPV most associated with cervical and other cancers. Thus, HPV vaccination has become an important component of adolescent preventive health care. As media evolves, more information about HPV vaccination is shifting to social media platforms such as Twitter. Health information consumed on social media may be especially influential for segments of society such as younger populations, as well as ethnic and racial minorities.

OBJECTIVE: The objectives of our study were to quantify HPV vaccine communication on …

Genomics And Csf Analyses Implicate Thyroid Hormone In Hippocampal Sclerosis Of Aging, Peter T. Nelson, Yuriko Katsumata, Kwangsik Nho, Sergey C. Artiushin, Gregory A. Jicha, Wang-Xia Wang, Erin L. Abner, Andrew J. Saykin, Walter A. Kukull, Alzheimer’S Disease Neuroimaging Initiative (Adni), David W. Fardo

Sanders-Brown Center on Aging Faculty Publications

We report evidence of a novel pathogenetic mechanism in which thyroid hormone dysregulation contributes to dementia in elderly persons. Two single nucleotide polymorphisms (SNPs) on chromosome 12p12 were the initial foci of our study: rs704180 and rs73069071. These SNPs were identified by separate research groups as risk alleles for non-Alzheimer’s neurodegeneration. We found that the rs73069071 risk genotype was associated with hippocampal sclerosis (HS) pathology among people with the rs704180 risk genotype (National Alzheimer’s Coordinating Center/Alzheimer’s Disease Genetic Consortium data; n = 2113, including 241 autopsy-confirmed HS cases). Furthermore, both rs704180 and rs73069071 risk genotypes were associated with widespread brain …

Mir-155 Expression And Correlation With Clinical Outcome In Pediatric Aml: A Report From Children's Oncology Group., Ranjani Ramamurthy, Maya Hughes, Valerie Morris, Hamid Bolouri, Robert B. Gerbing, Yi-Cheng Wang, Michael R. Loken, Susana C. Raimondi, Betsy A. Hirsch, A S. Gamis, Vivian G. Oehler, Todd A. Alonzo, Soheil Meshinchi

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Aberrant expression of microRNA-155 (miR-155) has been implicated in acute myeloid leukemia (AML) and associated with clinical outcome.

PROCEDURE: We evaluated miR-155 expression in 198 children with normal karyotype AML (NK-AML) enrolled in Children's Oncology Group (COG) AML trial AAML0531 and correlated miR-155 expression levels with disease characteristics and clinical outcome. Patients were divided into quartiles (Q1-Q4) based on miR-155 expression level, and disease characteristics were then evaluated and correlated with miR-155 expression.

RESULTS: MiR-155 expression varied over 4-log10-fold range relative to its expression in normal marrow with a median expression level of 0.825 (range 0.043-25.630) for the entire …

Administration Of Electroconvulsive Therapy For Depression Associated With Deep Brain Stimulation In A Patient With Post-Traumatic Parkinson's Disease: A Case Study, Miles G. Cunningham, Golnaz Yadollahikhales, Gordana Vitaliano, Craig Van Horne

Neurosurgery Faculty Publications

Background: Deep brain stimulation (DBS) has been shown to be effective for parkinsonian symptoms poorly responsive to medications. DBS is typically well-tolerated, as are the maintenance battery changes. Here we describe an adverse event during a battery replacement procedure that caused rapid onset of severe depression.

Case Presentation: The patient is a 58-year-old woman who was in a serious motor vehicle accident and sustained a concussion with loss of consciousness. Within weeks of the accident she began developing parkinsonian symptoms that progressively worsened over the subsequent 10 years. Responding poorly to medications, she received DBS, which controlled her movement symptoms. …

The Serotonin Transporter Promoter Polymorphism Moderates The Continuity Of Behavioral Inhibition In Early Childhood., Victoria C Johnson, Katie R Kryski, Haroon I Sheikh, Heather J Smith, Shiva M Singh, Elizabeth P Hayden

Brain and Mind Institute Researchers' Publications

Persistently elevated behavioral inhibition (BI) in children is a marker of vulnerability to psychopathology. However, little research has considered the joint influences of caregiver and child factors that may moderate the continuity of BI in early childhood, particularly genetic variants that may serve as markers of biological plasticity, such as the serotonin transporter linked polymorphic region (5-HTTLPR). We explored this issue in 371 preschoolers and their caregivers, examining whether parent characteristics (i.e., overinvolvement or anxiety disorder) and child 5-HTTLPR influenced the continuity of BI between ages 3 and 5. Measures were observational ratings of child BI, observational and questionnaire measures …

Resting-State Network-Specific Breakdown Of Functional Connectivity During Ketamine Alteration Of Consciousness In Volunteers., Vincent Bonhomme, Audrey Vanhaudenhuyse, Athena Demertzi, Marie-Aurélie Bruno, Oceane Jaquet, Mohamed Ali Bahri, Alain Plenevaux, Melanie Boly, Pierre Boveroux, Andrea Soddu, Jean François Brichant, Pierre Maquet, Steven Laureys

Brain and Mind Institute Researchers' Publications

BACKGROUND: Consciousness-altering anesthetic agents disturb connectivity between brain regions composing the resting-state consciousness networks (RSNs). The default mode network (DMn), executive control network, salience network (SALn), auditory network, sensorimotor network (SMn), and visual network sustain mentation. Ketamine modifies consciousness differently from other agents, producing psychedelic dreaming and no apparent interaction with the environment. The authors used functional magnetic resonance imaging to explore ketamine-induced changes in RSNs connectivity.

METHODS: Fourteen healthy volunteers received stepwise intravenous infusions of ketamine up to loss of responsiveness. Because of agitation, data from six subjects were excluded from analysis. RSNs connectivity was compared between absence of …

The Influence Of Age On The Diagnostic Performance Of White Blood Cell Count And Absolute Neutrophil Count In Suspected Pediatric Appendicitis., Richard G. Bachur, Peter S. Dayan, Nanette C. Dudley, Lalit Bajaj, Michelle D. Stevenson, Charles G. Macias, Manoj K. Mittal, Jonathan Bennett, Kelly A. Sinclair, Michael C. Monuteaux, Anupam B. Kharbanda

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVE: White blood cell (WBC) count and absolute neutrophil count (ANC) are a standard part of the evaluation of suspected appendicitis. Specific threshold values are utilized in clinical pathways, but the discriminatory value of WBC count and ANC may vary by age. The objective of this study was to investigate whether the diagnostic value of WBC count and ANC varies across age groups and whether diagnostic thresholds should be age-adjusted.

METHODS: This is a multicenter prospective observational study of patients aged 3-18 years who were evaluated for appendicitis. Receiver operator characteristic curves were developed to assess overall discriminative power of …

Usage Of Swi (Susceptibility Weighted Imaging) Acquired At 7t For Qualitative Evaluation Of Temporal Lobe Epilepsy Patients With Histopathological And Clinical Correlation: An Initial Pilot Study., Benjamin Y M Kwan, Fateme Salehi, Pavlo Ohorodnyk, Donald H Lee, Jorge G Burneo, Seyed M Mirsattari, David Steven, Robert Hammond, Terry M Peters, Ali R Khan

Brain and Mind Institute Researchers' Publications

OBJECTIVES: Ultra high field MRI at 7T is able to provide much improved spatial and contrast resolution which may aid in the diagnosis of hippocampal abnormalities. This paper presents a preliminary experience on qualitative evaluation of 7T MRI in temporal lobe epilepsy patients with a focus on comparison to histopathology.

METHODS: 7T ultra high field MRI data, using T1-weighted, T2*-weighted and susceptibility-weighted images (SWI), were acquired for 13 patients with drug resistant temporal lobe epilepsy (TLE) during evaluation for potential epilepsy surgery. Qualitative evaluation of the imaging data for scan quality and presence of hippocampal and temporal lobe abnormalities were …

Biallelic Mutations In Tbcd, Encoding The Tubulin Folding Cofactor D, Perturb Microtubule Dynamics And Cause Early-Onset Encephalopathy., Elisabetta Flex, Marcello Niceta, Serena Cecchetti, Isabelle Thiffault, Margaret G. Au, Alessandro Capuano, Emanuela Piermarini, Anna A. Ivanova, Joshua W. Francis, Giovanni Chillemi, Balasubramanian Chandramouli, Giovanna Carpentieri, Charlotte A. Haaxma, Andrea Ciolfi, Simone Pizzi, Ganka V. Douglas, Kara Levine, Antonella Sferra, Maria Lisa Dentici, Rolph R. Pfundt, Jean-Baptist Lepichon, Emily G. Farrow, Frank Baas, Fiorella Piemonte, Bruno Dallapiccola, John M. Graham, Carol J. Saunders, Enrico Bertini, Richard A. Kahn, David A. Koolen, Marco Tartaglia

Manuscripts, Articles, Book Chapters and Other Papers

Microtubules are dynamic cytoskeletal elements coordinating and supporting a variety of neuronal processes, including cell division, migration, polarity, intracellular trafficking, and signal transduction. Mutations in genes encoding tubulins and microtubule-associated proteins are known to cause neurodevelopmental and neurodegenerative disorders. Growing evidence suggests that altered microtubule dynamics may also underlie or contribute to neurodevelopmental disorders and neurodegeneration. We report that biallelic mutations in TBCD, encoding one of the five co-chaperones required for assembly and disassembly of the αβ-tubulin heterodimer, the structural unit of microtubules, cause a disease with neurodevelopmental and neurodegenerative features characterized by early-onset cortical atrophy, secondary hypomyelination, microcephaly, thin …

Neural Measures Reveal Implicit Learning During Language Processing., Laura J Batterink, Larry Y Cheng, Ken A Paller

Brain and Mind Institute Researchers' Publications

Language input is highly variable; phonological, lexical, and syntactic features vary systematically across different speakers, geographic regions, and social contexts. Previous evidence shows that language users are sensitive to these contextual changes and that they can rapidly adapt to local regularities. For example, listeners quickly adjust to accented speech, facilitating comprehension. It has been proposed that this type of adaptation is a form of implicit learning. This study examined a similar type of adaptation, syntactic adaptation, to address two issues: (1) whether language comprehenders are sensitive to a subtle probabilistic contingency between an extraneous feature (font color) and syntactic structure …

A Quantitative Comparison Of The Hemispheric, Areal, And Laminar Origins Of Sensory And Motor Cortical Projections To The Superior Colliculus Of The Cat., Blake E Butler, Nicole Chabot, Stephen G Lomber

Brain and Mind Institute Researchers' Publications

The superior colliculus (SC) is a midbrain structure central to orienting behaviors. The organization of descending projections from sensory cortices to the SC has garnered much attention; however, rarely have projections from multiple modalities been quantified and contrasted, allowing for meaningful conclusions within a single species. Here, we examine corticotectal projections from visual, auditory, somatosensory, motor, and limbic cortices via retrograde pathway tracers injected throughout the superficial and deep layers of the cat SC. As anticipated, the majority of cortical inputs to the SC originate in the visual cortex. In fact, each field implicated in visual orienting behavior makes a …

Mitochondrial Akt Regulation Of Hypoxic Tumor Reprogramming., Young Chan Chae, Valentina Vaira, M. Cecilia Caino, Hsin-Yao Tang, Jae Ho Seo, Andrew V. Kossenkov, Luisa Ottobrini, Cristina Martelli, Giovanni Lucignani, Irene Bertolini, Marco Locatelli, Kelly G. Bryant, Jagadish C. Ghosh, Sofia Lisanti, Bonsu Ku, Silvano Bosari, Lucia R. Languino, David W. Speicher, Dario C. Altieri

Department of Cancer Biology Faculty Papers

Hypoxia is a universal driver of aggressive tumor behavior, but the underlying mechanisms are not completely understood. Using a phosphoproteomics screen, we now show that active Akt accumulates in the mitochondria during hypoxia and phosphorylates pyruvate dehydrogenase kinase 1 (PDK1) on Thr346 to inactivate the pyruvate dehydrogenase complex. In turn, this pathway switches tumor metabolism toward glycolysis, antagonizes apoptosis and autophagy, dampens oxidative stress, and maintains tumor cell proliferation in the face of severe hypoxia. Mitochondrial Akt-PDK1 signaling correlates with unfavorable prognostic markers and shorter survival in glioma patients and may provide an "actionable" therapeutic target in cancer.

A Trial-By-Trial Window Into Sensorimotor Transformations In The Human Motor Periphery., Chao Gu, Daniel K Wood, Paul L Gribble, Brian D Corneil

Brain and Mind Institute Researchers' Publications

UNLABELLED: The appearance of a novel visual stimulus generates a rapid stimulus-locked response (SLR) in the motor periphery within 100 ms of stimulus onset. Here, we recorded SLRs from an upper limb muscle while humans reached toward (pro-reach) or away (anti-reach) from a visual stimulus. The SLR on anti-reaches encoded the location of the visual stimulus rather than the movement goal. Further, SLR magnitude was attenuated when subjects reached away from rather than toward the visual stimulus. Remarkably, SLR magnitudes also correlated with reaction times on both pro-reaches and anti-reaches, but did so in opposite ways: larger SLRs preceded shorter …

Effects Of Material Properties And Object Orientation On Precision Grip Kinematics., Vivian C Paulun, Karl R Gegenfurtner, Melvyn A Goodale, Roland W Fleming

Brain and Mind Institute Researchers' Publications

Successfully picking up and handling objects requires taking into account their physical properties (e.g., material) and position relative to the body. Such features are often inferred by sight, but it remains unclear to what extent observers vary their actions depending on the perceived properties. To investigate this, we asked participants to grasp, lift and carry cylinders to a goal location with a precision grip. The cylinders were made of four different materials (Styrofoam, wood, brass and an additional brass cylinder covered with Vaseline) and were presented at six different orientations with respect to the participant (0°, 30°, 60°, 90°, 120°, …

Rapid Decrement In The Effects Of The Ponzo Display Dissociates Action And Perception., Robert L Whitwell, Gavin Buckingham, James T Enns, Philippe A Chouinard, Melvyn A Goodale

Brain and Mind Institute Researchers' Publications

It has been demonstrated that pictorial illusions have a smaller influence on grasping than they do on perceptual judgments. Yet to date this work has not considered the reduced influence of an illusion as it is measured repeatedly. Here we studied this decrement in the context of a Ponzo illusion to further characterize the dissociation between vision for perception and for action. Participants first manually estimated the lengths of single targets in a Ponzo display with their thumb and index finger, then actually grasped these targets in another series of trials, and then manually estimated the target lengths again in …

Comparison Of A Powdered, Acidified Liquid, And Non-Acidified Liquid Human Milk Fortifier On Clinical Outcomes In Premature Infants., Melissa Thoene, Elizabeth Lyden, Kara Weishaar, Elizabeth Elliott, Ruomei Wu, Katelyn White, Hayley Timm, Ann Anderson-Berry

Journal Articles: Medical Nutrition

We previously compared infant outcomes between a powdered human milk fortifier (P-HMF) vs. acidified liquid HMF (AL-HMF). A non-acidified liquid HMF (NAL-HMF) is now commercially available. The purpose of this study is to compare growth and outcomes of premature infants receiving P-HMF, AL-HMF or NAL-HMF. An Institutional Review Board (IRB) approved retrospective chart review compared infant outcomes (born < 2000 g) who received one of three HMF. Growth, enteral nutrition, laboratory and demographic data were compared. 120 infants were included (P-HMF = 46, AL-HMF = 23, NAL-HMF = 51). AL-HMF infants grew slower in g/day (median 23.66 vs. P-HMF 31.27, NAL-HMF 31.74 (p < 0.05)) and in g/kg/day, median 10.59 vs. 15.37, 14.03 (p < 0.0001). AL-HMF vs. NAL-HMF infants were smaller at 36 weeks gestational age (median 2046 vs. 2404 g, p < 0.05). However AL-HMF infants received more daily calories (p = 0.21) and protein (p < 0.0001), mean 129 cal/kg, 4.2 g protein/kg vs. P-HMF 117 cal/kg, 3.7 g protein/kg , NAL-HMF 120 cal/kg, 4.0 g protein/kg. AL-HMF infants exhibited lower carbon dioxide levels after day of life 14 and 30 (p < 0.0001, p = 0.0038). Three AL-HMF infants (13%) developed necrotizing enterocolitis (NEC) vs. no infants in the remaining groups (p = 0.0056). A NAL-HMF is the most optimal choice for premature human milk-fed infants in a high acuity neonatal intensive care unit (NICU).

Cerebral Functional Connectivity Periodically (De)Synchronizes With Anatomical Constraints., Raphaël Liégeois, Erik Ziegler, Christophe Phillips, Pierre Geurts, Francisco Gómez, Mohamed Ali Bahri, B T Thomas Yeo, Andrea Soddu, Audrey Vanhaudenhuyse, Steven Laureys, Rodolphe Sepulchre

Brain and Mind Institute Researchers' Publications

This paper studies the link between resting-state functional connectivity (FC), measured by the correlations of fMRI BOLD time courses, and structural connectivity (SC), estimated through fiber tractography. Instead of a static analysis based on the correlation between SC and FC averaged over the entire fMRI time series, we propose a dynamic analysis, based on the time evolution of the correlation between SC and a suitably windowed FC. Assessing the statistical significance of the time series against random phase permutations, our data show a pronounced peak of significance for time window widths around 20-30 TR (40-60 s). Using the appropriate window …

Daclatasvir In Combination With Asunaprevir And Beclabuvir For Hepatitis C Virus Genotype 1 Infection With Compensated Cirrhosis., Andrew J Muir, Fred Poordad, Jacob Lalezari, Gregory Everson, Gregory J Dore, Robert Herring, Aasim Sheikh, Paul Kwo, Christophe Hézode, Paul J Pockros, Albert Tran, Joseph L. Yozviak Do, Facp, Nancy Reau, Alnoor Ramji, Katherine Stuart, Alexander J Thompson, John Vierling, Bradley Freilich, James Cooper, Wayne Ghesquiere, Rong Yang, Fiona Mcphee, Eric A Hughes, E Scott Swenson, Philip D Yin

Joseph L Yozviak DO, FACP

IMPORTANCE: Effective and well-tolerated, interferon-free regimens are needed for treatment of patients with chronic hepatitis C virus (HCV) infection and cirrhosis.

OBJECTIVE: All-oral therapy with daclatasvir (nonstructural protein 5A [NS5A] inhibitor), asunaprevir (NS3 protease inhibitor), and beclabuvir (nonnucleoside NS5B inhibitor), with or without ribavirin, was evaluated in patients with HCV genotype 1 infection and compensated cirrhosis.

DESIGN, SETTING, AND PARTICIPANTS: The UNITY-2 study was conducted between December 2013 and October 2014 at 49 outpatient sites in the United States, Canada, France, and Australia. Patients were treated for 12 weeks, with 24 weeks of follow-up after completion of treatment. Adult patients …

Hyperpolarized 3he Magnetic Resonance Imaging Ventilation Defects In Asthma: Relationship To Airway Mechanics, Del Leary, Sarah Svenningsen, Fumin Guo, Swati Bhatawadekar, Grace Parraga, Geoffrey N Maksym

Medical Biophysics Publications

In patients with asthma, magnetic resonance imaging (MRI) provides direct measurements of regional ventilation heterogeneity, the etiology of which is not well-understood, nor is the relationship of ventilation abnormalities with lung mechanics. In addition, respiratory resistance and reactance are often abnormal in asthmatics and the frequency dependence of respiratory resistance is thought to reflect ventilation heterogeneity. We acquiredMRIventilation defect maps, forced expiratory volume in one-second (FEV1), and airways resistance (Raw) measurements, and used a computational airway model to explore the relationship of ventilation defect percent (VDP) with simulated measurements of respiratory system resistance (Rrs) and reactance (Xrs).MRIventilation defect maps were …

Functional Plasticity In Somatosensory Cortex Supports Motor Learning By Observing., Heather R Mcgregor, Joshua G A Cashaback, Paul L Gribble

Brain and Mind Institute Researchers' Publications

An influential idea in neuroscience is that the sensory-motor system is activated when observing the actions of others [1, 2]. This idea has recently been extended to motor learning, in which observation results in sensory-motor plasticity and behavioral changes in both motor and somatosensory domains [3-9]. However, it is unclear how the brain maps visual information onto motor circuits for learning. Here we test the idea that the somatosensory system, and specifically primary somatosensory cortex (S1), plays a role in motor learning by observing. In experiment 1, we applied stimulation to the median nerve to occupy the somatosensory system with …

Propofol-Induced Frontal Cortex Disconnection: A Study Of Resting-State Networks, Total Brain Connectivity, And Mean Bold Signal Oscillation Frequencies., Pieter Guldenmund, Ithabi S Gantner, Katherine Baquero, Tushar Das, Athena Demertzi, Pierre Boveroux, Vincent Bonhomme, Audrey Vanhaudenhuyse, Marie-Aurélie Bruno, Olivia Gosseries, Quentin Noirhomme, Muriëlle Kirsch, Mélanie Boly, Adrian M Owen, Steven Laureys, Francisco Gómez, Andrea Soddu

Brain and Mind Institute Researchers' Publications

Propofol is one of the most commonly used anesthetics in the world, but much remains unknown about the mechanisms by which it induces loss of consciousness. In this resting-state functional magnetic resonance imaging study, we examined qualitative and quantitative changes of resting-state networks (RSNs), total brain connectivity, and mean oscillation frequencies of the regional blood oxygenation level-dependent (BOLD) signal, associated with propofol-induced mild sedation and loss of responsiveness in healthy subjects. We found that detectability of RSNs diminished significantly with loss of responsiveness, and total brain connectivity decreased strongly in the frontal cortex, which was associated with increased mean oscillation …

Revising The Bis/Bas Scale To Study Development: Measurement Invariance And Normative Effects Of Age And Sex From Childhood Through Adulthood., David Pagliaccio, Katherine R Luking, Andrey P Anokhin, Ian H Gotlib, Elizabeth P Hayden, Thomas M Olino, Chun-Zi Peng, Greg Hajcak, Deanna M Barch

Brain and Mind Institute Researchers' Publications

Carver and White's (1994) Behavioral Inhibition System/Behavioral Activation System (BIS/BAS) Scales have been useful tools for studying individual differences in reward-punishment sensitivity; however, their factor structure and invariance across development have not been well tested. In the current study, we examined the factor structure of the BIS/BAS Scales across 5 age groups: 6- to 10-year-old children (N = 229), 11- to 13-year-old early adolescents (N = 311), 14- to 16-year-old late adolescents (N = 353), 18- to 22-year-old young adults (N = 844), and 30- to 45-year-old adults (N = 471). Given poor fit of the standard 4-factor model (BIS, …

Variants In Cxcr4 Associate With Juvenile Idiopathic Arthritis Susceptibility., Terri H. Finkel, Jin Li, Zhi Wei, Wei Wang, Haitao Zhang, Edward M. Behrens, Emma L. Reuschel, Sophie Limou, Carol Wise, Marilynn Punaro, Mara L. Becker, Jane E. Munro, Berit Flatø, Øystein Førre, Susan D. Thompson, Carl D. Langefeld, David N. Glass, Joseph T. Glessner, Cecilia E. Kim, Edward Frackelton, Debra K. Shivers, Kelly A. Thomas, Rosetta M. Chiavacci, Cuiping Hou, Kexiang Xu, James Snyder, Haijun Qiu, Frank Mentch, Kai Wang, Cheryl A. Winkler, Benedicte A. Lie, Justine A. Ellis, Hakon Hakonarson

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease among children, the etiology of which involves a strong genetic component, but much of the underlying genetic determinants still remain unknown. Our aim was to identify novel genetic variants that predispose to JIA.

METHODS: We performed a genome-wide association study (GWAS) and replication in a total of 1166 JIA cases and 9500 unrelated controls of European ancestry. Correlation of SNP genotype and gene expression was investigated. Then we conducted targeted resequencing of a candidate locus, among a subset of 480 cases and 480 controls. SUM test was performed …

Category Learning In Older Adulthood: A Study Of The Shepard, Hovland, And Jenkins (1961) Tasks., Rahel Rabi, John Paul Minda

Brain and Mind Institute Researchers' Publications

Shepard, Hovland, and Jenkins (1961) examined the categorization abilities of younger adults using tasks involving single-dimensional rule learning, disjunctive rule learning, and family resemblance learning. The current study examined category learning in older adults using this well-known category set. Older adults, like younger adults, found category tasks with a single relevant dimension the easiest to learn. In contrast to younger adults, older adults found complex disjunctive rule-based categories harder to learn than family resemblance based categories. Disjunctive rule-based category learning appeared to be the most difficult for older adults to learn because this category set placed the heaviest demands on …

Effects Of A Consistent Target Or Masker Voice On Target Speech Intelligibility In Two- And Three-Talker Mixtures., Fabienne Samson, Ingrid S Johnsrude

Brain and Mind Institute Researchers' Publications

When the spatial location or identity of a sound is held constant, it is not masked as effectively by competing sounds. This suggests that experience with a particular voice over time might facilitate perceptual organization in multitalker environments. The current study examines whether listeners benefit from experience with a voice only when it is the target, or also when it is a masker, using diotic presentation and a closed-set task (coordinate response measure). A reliable interaction was observed such that, in two-talker mixtures, consistency of masker or target voice over 3-7 trials significantly benefited target recognition performance, whereas in three-talker …

Molecular Analyses Of Circadian Gene Variants Reveal Sex-Dependent Links Between Depression And Clocks, S-Q Shi, M. J. White, H. M. Borsetti, Julie S. Pendergast, A. Hida, C. M. Ciarleglio, P. A. De Verteuil, A. G. Cadar, C. Cala, D. G. Mcmahon, R. C. Shelton, S. M. Williams, C. H. Johnson

Biology Faculty Publications

An extensive literature links circadian irregularities and/or sleep abnormalities to mood disorders. Despite the strong genetic component underlying many mood disorders, however, previous genetic associations between circadian clock gene variants and major depressive disorder (MDD) have been weak. We applied a combined molecular/functional and genetic association approach to circadian gene polymorphisms in sex-stratified populations of control subjects and case subjects suffering from MDD. This approach identified significant sex-dependent associations of common variants of the circadian clock genes hClock, hPer3 and hNpas2 with major depression and demonstrated functional effects of these polymorphisms on the expression or activity of the hCLOCK …

In Vivo Mri Signatures Of Hippocampal Subfield Pathology In Intractable Epilepsy., Maged Goubran, Boris C Bernhardt, Diego Cantor-Rivera, Jonathan C Lau, Charlotte Blinston, Robert R Hammond, Sandrine De Ribaupierre, Jorge G Burneo, Seyed M Mirsattari, David A Steven, Andrew G Parrent, Andrea Bernasconi, Neda Bernasconi, Terry M Peters, Ali R Khan

Brain and Mind Institute Researchers' Publications

OBJECTIVES: Our aim is to assess the subfield-specific histopathological correlates of hippocampal volume and intensity changes (T1, T2) as well as diff!usion MRI markers in TLE, and investigate the efficacy of quantitative MRI measures in predicting histopathology in vivo.

EXPERIMENTAL DESIGN: We correlated in vivo volumetry, T2 signal, quantitative T1 mapping, as well as diffusion MRI parameters with histological features of hippocampal sclerosis in a subfield-specific manner. We made use of on an advanced co-registration pipeline that provided a seamless integration of preoperative 3 T MRI with postoperative histopathological data, on which metrics of cell loss and gliosis were quantitatively …

Cd33 Expression And Its Association With Gemtuzumab Ozogamicin Response: Results From The Randomized Phase Iii Children's Oncology Group Trial Aaml0531., Jessica A. Pollard, Michael Loken, Robert B. Gerbing, Susana C. Raimondi, Betsy A. Hirsch, Richard Aplenc, Irwin D. Bernstein, Alan S. Gamis, Todd A. Alonzo, Soheil Meshinchi

Manuscripts, Articles, Book Chapters and Other Papers

PURPOSE: CD33 is variably expressed on acute myeloid leukemia (AML) blasts and is targeted by gemtuzumab ozogamicin (GO). GO has shown benefit in both adult and pediatric AML trials, yet limited data exist about whether GO response correlates with CD33 expression level.

PATIENTS AND METHODS: CD33 expression levels were prospectively quantified by multidimensional flow cytometry in 825 patients enrolled in Children's Oncology Group AAML0531 and correlated with response to GO.

RESULTS: Patients with low CD33 expression (lowest quartile of expression [Q1]) had no benefit with the addition of GO to conventional chemotherapy (relapse risk [RR]: GO 36% v No-GO 34%, …

Cddo-Me Redirects Activation Of Breast Tumor Associated Macrophages, Michael S. Ball, Emilie P. Shipman, Hyunjung Kim, Karen T. Liby, Patricia A. Pioli

Dartmouth Scholarship

Tumor-associated macrophages can account for up to 50% of the tumor mass in breast cancer patients and high TAM density is associated with poor clinical prognosis. Because TAMs enhance tumor growth, development, and metastatic potential, redirection of TAM activation may have significant therapeutic benefit. Our studies in primary human macrophages and murine breast TAMs suggest that the synthetic oleanane triterpenoid CDDO-methyl ester (CDDO-Me) reprograms the activation profile of TAMs from tumor-promoting to tumor-inhibiting. We show that CDDO-Me treatment inhibits expression of IL-10 and VEGF in stimulated human M2 macrophages and TAMs but increases expression of TNF-α and IL-6. Surface expression …

Herpes Simplex Virus And Interferon Signaling Induce Novel Autophagic Clusters In Sensory Neurons, Sarah Katzenell, David A. Leib

Dartmouth Scholarship

Herpes simplex virus 1 (HSV-1) establishes lifelong infection in the neurons of trigeminal ganglia (TG), cycling between productive infection and latency. Neuronal antiviral responses are driven by type I interferon (IFN) and are crucial to controlling HSV-1 virulence. Autophagy also plays a role in this neuronal antiviral response, but the mechanism remains obscure. In this study, HSV-1 infection of murine TG neurons triggered unusual clusters of autophagosomes, predominantly in neurons lacking detectable HSV-1 antigen. Treatment of neurons with IFN-β induced a similar response, and cluster formation by infection or IFN treatment was dependent upon an intact IFN-signaling pathway. The autophagic …