Digital Commons Network^™

Baseline White Matter Hyperintensities And Hippocampal Volume Are Associated With Conversion From Normal Cognition To Mild Cognitive Impairment In The Framingham Offspring Study., Katherine J Bangen, Sarah R Preis, Lisa Delano-Wood, Philip A Wolf, David J Libon, Mark W Bondi, Rhoda Au, Charles Decarli, Adam M Brickman

Rowan-Virtua School of Osteopathic Medicine Departmental Research

INTRODUCTION: We examined associations between magnetic resonance imaging (MRI) markers of cerebrovascular disease and neurodegeneration with mild cognitive impairment (MCI) diagnosis at baseline and conversion from normal cognition to MCI at follow-up.

METHODS: Framingham Offspring participants underwent brain MRI and neuropsychological assessment at baseline (n=1049) and follow-up (n=561). Participants were classified at baseline and at follow-up as cognitively normal or MCI using sensitive neuropsychological criteria. White matter hyperintensity (WMH) volume, covert brain infarcts, hippocampal volume, and total cerebral brain volume were quantified.

RESULTS: Baseline measures of WMH and hippocampal volume were associated with MCI status cross-sectionally and also with conversion …

Assessing Working Memory In Mild Cognitive Impairment With Serial Order Recall., Sheina Emrani, David J Libon, Melissa Lamar, Catherine C Price, Angela L Jefferson, Katherine A Gifford, Timothy J Hohman, Daniel A Nation, Lisa Delano-Wood, Amy Jak, Katherine J Bangen, Mark W Bondi, Adam M Brickman, Jennifer Manly, Rodney Swenson, Rhoda Au, Consortium For Clinical And Epidemiological Neuropsychological Data Analysis (Cenda)

Rowan-Virtua School of Osteopathic Medicine Departmental Research

BACKGROUND: Working memory (WM) is often assessed with serial order tests such as repeating digits backward. In prior dementia research using the Backward Digit Span Test (BDT), only aggregate test performance was examined.

OBJECTIVE: The current research tallied primacy/recency effects, out-of-sequence transposition errors, perseverations, and omissions to assess WM deficits in patients with mild cognitive impairment (MCI).

METHODS: Memory clinic patients (n = 66) were classified into three groups: single domain amnestic MCI (aMCI), combined mixed domain/dysexecutive MCI (mixed/dys MCI), and non-MCI where patients did not meet criteria for MCI. Serial order/WM ability was assessed by asking participants to repeat …

Centrilobular Emphysema And Coronary Artery Calcification: Mediation Analysis In The Spiromics Cohort, Surya P. Bhatt, Hrudaya P. Nath, Young-Il Kim, Rekha Ramachandran, Jubal R. Watts, Nina L.J. Terry, Sushil Sonavane, Swati P. Deshmane, Prescott G. Woodruff, Elizabeth C. Oelsner, Sandeep Bodduluri, Meilan K. Han, Wassim W. Labaki, J. Michael Wells, Fernando J. Martinez, R. Graham Barr, Mark T. Dransfield, Spiromics Investigators

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is associated with a two-to-five fold increase in the risk of coronary artery disease independent of shared risk factors. This association is hypothesized to be mediated by systemic inflammation but this link has not been established.

METHODS: We included 300 participants enrolled in the SPIROMICS cohort, 75 each of lifetime non-smokers, smokers without airflow obstruction, mild-moderate COPD, and severe-very severe COPD. We quantified emphysema and airway disease on computed tomography, characterized visual emphysema subtypes (centrilobular and paraseptal) and airway disease, and used the Weston visual score to quantify coronary artery calcification (CAC). We used …

A New Model Of Wheezing Severity In Young Children Using The Validated Isaac Wheezing Module: A Latent Variable Approach With Validation In Independent Cohorts., Steven M. Brunwasser Phd, Tebeb Gebretsadik, Diane R Gold, Kedir N Turi, Cosby A Stone, Soma Datta, James E Gern, Tina V Hartert

College of Science & Mathematics Departmental Research

BACKGROUND: The International Study of Asthma and Allergies in Children (ISAAC) Wheezing Module is commonly used to characterize pediatric asthma in epidemiological studies, including nearly all airway cohorts participating in the Environmental Influences on Child Health Outcomes (ECHO) consortium. However, there is no consensus model for operationalizing wheezing severity with this instrument in explanatory research studies. Severity is typically measured using coarsely-defined categorical variables, reducing power and potentially underestimating etiological associations. More precise measurement approaches could improve testing of etiological theories of wheezing illness.

METHODS: We evaluated a continuous latent variable model of pediatric wheezing severity based on four ISAAC …

Which Neuropsychological Functions Predict Various Processing Speed Components In Children With And Without Attention-Deficit/Hyperactivity Disorder?, Sarah A Vadnais, Michelle Y Kibby, Audreyana C Jagger-Rickels

Publications

We identified statistical predictors of four processing speed (PS) components in a sample of 151 children with and without attention-deficit/hyperactivity disorder (ADHD). Performance on perceptual speed was predicted by visual attention/short-term memory, whereas incidental learning/psychomotor speed was predicted by verbal working memory. Rapid naming was predictive of each PS component assessed, and inhibition predicted all but one task, suggesting a shared need to identify/retrieve stimuli rapidly and inhibit incorrect responding across PS components. Hence, we found both shared and unique predictors of perceptual, cognitive, and output speed, suggesting more specific terminology should be used in future research on PS in …

Homelessness Predicts Attrition But Not Alcohol Abstinence In Outpatients Experiencing Co-Occurring Alcohol Dependence And Serious Mental Illness., Emily Leickly, Jordan Skalisky, Oladunni Oluwoye, Sterling M Mcpherson, Debra Srebnik, John M Roll, Richard K Ries, Michael G Mcdonell

Articles, Abstracts, and Reports

BACKGROUND: Adults experiencing homelessness and serious mental illnesses (SMI) are at an increased risk of poor mental health and treatment outcomes compared with stably housed adults with SMI. The additional issue of alcohol misuse further complicates the difficulties of those living with homelessness and SMI. In this secondary data analysis, the authors investigated the impact of homelessness on attrition and alcohol use in a contingency management (CM) intervention that rewarded alcohol abstinence in outpatients with SMI.

METHODS: The associations between housing status and attrition and alcohol abstinence during treatment, as assessed by ethyl glucuronide (EtG) urine tests, were evaluated in …

Temporal And Geospatial Trends Of Pediatric Cancer Incidence In Nebraska Over A 24-Year Period, Evi A. Farazi, Shinobu Watanabe-Galloway, L. Westman, B. Rettig, P. Hunt, R. Cammack, John W. Sparks, Don W. Coulter

Journal Articles: Epidemiology

BACKGROUND: Data from the Surveillance, Epidemiology, and End Results (SEER) revealed that the incidence of pediatric cancer in Nebraska exceeded the national average during 2009-2013. Further investigation could help understand these patterns.

METHODS: This retrospective cohort study investigated pediatric cancer (0-19 years old) age adjusted incidence rates (AAR) in Nebraska using the Nebraska Cancer Registry. SEER AARs were also calculated as a proxy for pediatric cancer incidence in the United States (1990-2013) and compared to the Nebraska data. Geographic Information System (GIS) mapping was also used to display the spatial distribution of cancer in Nebraska at the county level. Finally, …

Analytical High-Resolution Electron Microscopy Reveals Organ-Specific Nanoceria Bioprocessing, Uschi M. Graham, Robert A. Yokel, Alan K. Dozier, Lawrence Drummy, Krishnamurthy Mahalingam, Michael T. Tseng, Eileen Birch, Joseph Fernback

Pharmaceutical Sciences Faculty Publications

This is the first utilization of advanced analytical electron microscopy methods, including high-resolution transmission electron microscopy, high-angle annular dark field scanning transmission electron microscopy, electron energy loss spectroscopy, and energy-dispersive X-ray spectroscopy mapping to characterize the organ-specific bioprocessing of a relatively inert nanomaterial (nanoceria). Liver and spleen samples from rats given a single intravenous infusion of nanoceria were obtained after prolonged (90 days) in vivo exposure. These advanced analytical electron microscopy methods were applied to elucidate the organ-specific cellular and subcellular fate of nanoceria after its uptake. Nanoceria is bioprocessed differently in the spleen than in the liver.

Factors Contributing To Australian Adolescents’ Self-Report Of Their Motor Skill Competence, Amanda Timler, Fleur Mcintyre, Beth Hands

Health Sciences Papers and Journal Articles

An adolescents motor skill competence can affect areas such as sports participation, social activities and future academic or employment decisions. The Adolescent Motor Competence Questionnaire (AMCQ) is a 26-item questionnaire that uses a four point Likert response (never, sometimes, frequently, always) to assess motor-related activities during adolescence. This study aims to provide evidence of the construct validity using Principle Component Analysis (PCA) and to identify factors that contributed to Australian adolescent self-reported motor competence. A final aim was to determine whether individual item responses differed between males and females. The AMCQ was completed by 160 adolescents (M_age = 14.45 …

Genotype-Phenotype Study In Patients With Valosin-Containing Protein Mutations Associated With Multisystem Proteinopathy, Ebaa Al-Obeidi, Sejad Al-Tahan, Abhilasha Surampalli, Namita Goyal, Annabel K. Wang, Andreas Hermann, Molly Omizo, Charles D. Smith, Tahseen Mozaffar, Virginia Kimonis

Neurology Faculty Publications

Mutations in valosin‐containing protein (VCP), an ATPase involved in protein degradation and autophagy, cause VCP disease, a progressive autosomal dominant adult onset multisystem proteinopathy. The goal of this study is to examine if phenotypic differences in this disorder could be explained by the specific gene mutations. We therefore studied 231 individuals (118 males and 113 females) from 36 families carrying 15 different VCP mutations. We analyzed the correlation between the different mutations and prevalence, age of onset and severity of myopathy, Paget's disease of bone (PDB), and frontotemporal dementia (FTD), and other comorbidities. Myopathy, PDB and FTD was present in …

Gender Differences Among Professional Football Fans: Serious Leisure, Emotional Expressivity, And Cognitive Distortions, Megan E. Wolensky

PCOM Psychology Dissertations

Increasingly, people report that leisure activity gives their lives meaning and significantly contributes to the formation of their personal identities. In fact, many individuals rank leisure activities as essential as work, family, and religion. (Gillespie, Leffler, & Lerner, 2010; Stebbins, 1992). Recent research has demonstrated that leisure involvement provides psychological benefits that contribute to wellbeing for both men and women (Caltabiano, 1995; Kim, Heo, Lee, & Kim, 2015). National Football League (NFL) fandom in the U.S. has been identified as a leisure activity that supersedes traditional gender norms and provides opportunities for family and group involvement. Although fandom has been …

Effect Of Hemiepiphysiodesis On The Growth Plate: The Histopathological Changes And Mechanism Exploration Of Recurrence In Mini Pig Model., Jing Ding, Jin He, Zhi-Qiang Zhang, Zhen-Kai Wu, Fang-Chun Jin

Manuscripts, Articles, Book Chapters and Other Papers

Purpose: Hemiepiphysiodesis has been widely used to correct angular deformity of long bone in immature patients. However, there is a limited knowledge about the biomechanical effect of this technique on the histopathological changes of the growth plate and the mechanism of recurrence of malformation after implant removal. We aimed to evaluate the biomechanical effect of hemiepiphysiodesis on the histopathological changes of the growth plate and the mechanism of recurrence of malformation after implant removal in Bama miniature pigs, and to explore the role of asymmetric stress during this procedure.

Methods: Eight 3-month-old male Bama miniature pigs sustained surgeries on the …

Cetuximab Plus Carboplatin And Paclitaxel With Or Without Bevacizumab Versus Carboplatin And Paclitaxel With Or Without Bevacizumab In Advanced Nsclc (Swog S0819): A Randomised, Phase 3 Study, Roy S. Herbst, Mary W. Redman, Edward S. Kim, Thomas J. Semrad, Lyudmila Bazhenova, Gregory Masters, Kurt Oettel, Perry Guaglianone, Christopher Reynolds, Anand Karnad, Susanne M. Arnold, Marileila Varella-Garcia, James Moon, Philip C. Mack, Charles D. Blanke, Fred R. Hirsch, Karen Kelly, David R. Gandara

Markey Cancer Center Faculty Publications

Background

EGFR antibodies have shown promise in patients with advanced non-small-cell lung cancer (NSCLC), particularly with squamous cell histology. We hypothesised that EGFR copy number by fluorescence in-situ hybridisation (FISH) can identify patients most likely to benefit from these drugs combined with chemotherapy and we aimed to explore the activity of cetuximab with chemotherapy in patients with advanced NSCLC who are EGFR FISH-positive.

Methods

We did this open-label, phase 3 study (SWOG S0819) at 277 sites in the USA and Mexico. We randomly assigned (1:1) eligible patients with treatment-naive stage IV NSCLC to receive paclitaxel (200 mg/m ²; every …

Nanoparticle Orientation To Control Rna Loading And Ligand Display On Extracellular Vesicles For Cancer Regression, Fengmei Pi, Daniel W. Binzel, Tae Jin Lee, Zhefeng Li, Meiyan Sun, Piotr G. Rychahou, Hui Li, Farzin Haque, Shaoying Wang, Carlo M. Croce, Bin Guo, B. Mark Evers, Peixuan Guo

Markey Cancer Center Faculty Publications

Nanotechnology offers many benefits, and here we report an advantage of applying RNA nanotechnology for directional control. The orientation of arrow-shaped RNA was altered to control ligand display on extracellular vesicle membranes for specific cell targeting, or to regulate intracellular trafficking of small interfering RNA (siRNA) or microRNA (miRNA). Placing membrane-anchoring cholesterol at the tail of the arrow results in display of RNA aptamer or folate on the outer surface of the extracellular vesicle. In contrast, placing the cholesterol at the arrowhead results in partial loading of RNA nanoparticles into the extracellular vesicles. Taking advantage of the RNA ligand for …

Global Mapping Of Transcription Factor Motifs In Human Aging., David Alfego, Ulrich Rodeck, Andres Kriete

Department of Dermatology and Cutaneous Biology Faculty Papers

Biological aging is a complex process dependent on the interplay of cell autonomous and tissue contextual changes which occur in response to cumulative molecular stress and manifest through adaptive transcriptional reprogramming. Here we describe a transcription factor (TF) meta-analysis of gene expression datasets accrued from 18 tissue sites collected at different biological ages and from 7 different in-vitro aging models. In-vitro aging platforms included replicative senescence and an energy restriction model in quiescence (ERiQ), in which ATP was transiently reduced. TF motifs in promoter regions of trimmed sets of target genes were scanned using JASPAR and TRANSFAC. TF signatures established …

Determination Of An Optimal Response Cut-Off Able To Predict Progression-Free Survival In Patients With Well-Differentiated Advanced Pancreatic Neuroendocrine Tumours Treated With Sunitinib: An Alternative To The Current Recist-Defined Response., Angela Lamarca, Jorge Barriuso, Matthew Kulke, Ivan Borbath, Heinz-Josef Lenz, Jean Luc Raoul, Neal J. Meropol, Catherine Lombard-Bohas, James Posey, Sandrine Faivre, Eric Raymond, Juan W. Valle

Department of Medical Oncology Faculty Papers

BACKGROUND: Sunitinib prolongs progression-free survival (PFS) in patients with advanced pancreatic neuroendocrine tumours (pNET). Response Evaluation Criteria in Solid Tumors (RECIST)-defined partial responses (PR; classically defined as ⩾30% size decrease from baseline) are infrequent.

METHODS: Individual data of pNET patients from the phase II [NCT00056693] and pivotal phase III [NCT00428597] trials of sunitinib were analysed in this investigator-initiated, post hoc study. The primary objective was to determine the optimal RECIST (v.1.0) response cut-off value to identify patients who were progression-free at 11 months (median PFS in phase III trial); and the most informative time-point (highest area under the curve (AUC) …

Longo: An R Package For Interactive Gene Length Dependent Analysis For Neuronal Identity, Matthew J. Mccoy, Alexander J. Paul, Matheus B. Victor, Michelle Richner, Harrison W. Gabel, Haijun Gong, Andrew S. Yoo, Tae-Hyuk Ahn

Open Access Publications

Motivation: Reprogramming somatic cells into neurons holds great promise to model neuronal development and disease. The efficiency and success rate of neuronal reprogramming, however, may vary between different conversion platforms and cell types, thereby necessitating an unbiased, systematic approach to estimate neuronal identity of converted cells. Recent studies have demonstrated that long genes (>100 kb from transcription start to end) are highly enriched in neurons, which provides an opportunity to identify neurons based on the expression of these long genes.

Results: We have developed a versatile R package, LONGO, to analyze gene expression based on gene length. We propose …

Selective Inhibition Of The P38Α Mapk-Mk2 Axis Inhibits Inflammatory Cues Including Inflammasome Priming Signals, Chun Wang, Yael Alippe, Yousef Abu-Amer, Gabriel Mbalaviele, Et Al

Open Access Publications

p38α activation of multiple effectors may underlie the failure of global p38α inhibitors in clinical trials. A unique inhibitor (CDD-450) was developed that selectively blocked p38α activation of the proinflammatory kinase MK2 while sparing p38α activation of PRAK and ATF2. Next, the hypothesis that the p38α-MK2 complex mediates inflammasome priming cues was tested. CDD-450 had no effect on NLRP3 expression, but it decreased IL-1β expression by promoting IL-1β mRNA degradation. Thus, IL-1β is regulated not only transcriptionally by NF-κB and posttranslationally by the inflammasomes but also posttranscriptionally by p38α-MK2. CDD-450 also accelerated TNF-α and IL-6 mRNA decay, inhibited inflammation in …

Amygdala-Frontal Connectivity Predicts Internalizing Symptom Recovery Among Inpatient Adolescents, Amanda Venta, Carla Sharp, Michelle Patriquin, Ramiro Salas, Elizabeth Newlin, Kaylah Curtis, Philip Baldwin, Christopher Fowler, B Christopher Frueh

Staff and Researcher Publications

Background: The possibility of using biological measures to predict the trajectory of symptoms among adolescent psychiatric inpatients has important implications. This study aimed to examine emotion regulation ability (measured via self-report) and a hypothesized proxy in resting-state functional connectivity [RSFC] between the amygdala and frontal brain regions as baseline predictors of internalizing symptom recovery during inpatient care.

Methods: 196 adolescents (61% female; Mage = 15.20; SD = 1.48) completed the Achenbach Brief Problem Monitor (BPM) each week during their inpatient care. RSFC (n = 45) and self-report data of emotion regulation (n = 196) were collected at baseline.

Results: The …

Clinical Utility Of The Dsm-5 Alternative Model For Borderline Personality Disorder: Differential Diagnostic Accuracy Of The Bfi, Scid-Ii-Pq, And Pid-5, J Christopher Fowler, Alok Madan, Jon G Allen, Michelle Patriquin, Carla Sharp, John M Oldham, B Christopher Frueh

Staff and Researcher Publications

Background: With the publication of DSM 5 alternative model for personality disorders it is critical to assess the components of the model against evidence-based models such as the five factor model and the DSM-IV-TR categorical model. This study explored the relative clinical utility of these models in screening for borderline personality disorder (BPD).

Methods: Receiver operator characteristics and diagnostic efficiency statistics were calculated for three personality measures to ascertain the relative diagnostic efficiency of each measure. A total of 1653 adult inpatients at a specialist psychiatric hospital completed SCID-II interviews. Sample 1 (n=653) completed the SCID-II interviews, SCID-II Questionnaire (SCID-II-PQ) …

Left Atrial Structure And Function In Hypertrophic Cardiomyopathy Sarcomere Mutation Carriers With And Without Left Ventricular Hypertrophy, Hoshang Farhad, Sara B Seidelmann, Davis Vigneault, Siddique A Abbasi, Eunice Yang, Sharlene M Day, Steven D Colan, Mark W Russell, Jeffrey Towbin, Mark V Sherrid, Charles E Canter, Ling Shi, Michael Jerosch-Herold, David A Bluemke, Carolyn Ho, Tomas G Neilan

Open Access Publications

BACKGROUND: Impaired left atrial (LA) function is an early marker of cardiac dysfunction and predictor of adverse cardiac events. Herein, we assess LA structure and function in hypertrophy in hypertrophic cardiomyopathy (HCM) sarcomere mutation carriers with and without left ventricular hypertrophy (LVH).

METHOD: Seventy-three participants of the HCMNet study who underwent cardiovascular magnetic resonance (CMR) imaging were studied, including mutation carriers with overt HCM (n = 34), preclinical mutation carriers without HCM (n = 24) and healthy, familial controls (n = 15).

RESULTS: LA volumes were similar between preclinical, control and overt HCM cohorts after covariate adjustment. However, there was …

Improved Survival And Tumor Control With Interleukin-2 Is Associated With The Development Of Immune-Related Adverse Events: Data From The Proclaim, Brendan Curti, Gregory A Daniels, David F Mcdermott, Joseph I Clark, Howard L Kaufman, Theodore F Logan, Jatinder Singh, Meenu Kaur, Theresa L Luna, Nancy Gregory, Michael A Morse, Michael K K Wong, Janice P Dutcher

Articles, Abstracts, and Reports

BACKGROUND: Immune related adverse events (irAEs) are associated with immunotherapy for cancer and while results suggest improvement in tumor control and overall survival in those experiencing irAEs, the long-term impact is debated. We evaluated irAE reports related to high dose interleukin-2 therapy (IL-2) documented in the PROCLAIM

METHODS: Reports on 1535 patients, including 623 with metastatic melanoma (mM) and 919 with metastatic renal cell cancer (mRCC) (7 patients had both diseases), were queried for irAEs. The timing of the event was categorized as occurring before, during or after IL-2 or related to any checkpoint inhibitor (CPI). mM patients and mRCC …

Maternal Depressive Symptoms And Child Behavior Among Mexican Women And Their Children., Emily P Flynn, Esther O Chung, Emily J Ozer, Lia C H Fernald

Articles, Abstracts, and Reports

Over 50% of mothers in rural Mexico have high depressive symptoms, and their children's health and development are likely to be negatively affected. A critical question is whether children vary in their vulnerability to the effects of high maternal depressive symptoms according to their indigenous ethnicity, maternal education, or household wealth. Our sample included 4442 mothers and 5503 children from an evaluation of Mexico's social welfare program. Maternal depressive symptoms were assessed using the Center for Epidemiologic Studies Depression (CES-D) Scale, and child behavior was measured using an adapted version of the Behavior Problems Index (BPI). Multiple linear regression models …

Latino Male College Students' Identities, Psychological Stress, And Coping Mechanisms, Ana E. Ramirez

Dissertations

Latino male college students’ identities impact their personal experiences, academic achievement, and well-being. This qualitative study uses a narrative inquiry approach to research Latino male college students’ racial and ethnic, gender, and academic identities and to investigate how these identities impact their psychological stress and the coping mechanisms they implement to manage their stress. Latino males undergo an identity development in which they engage in negotiating their gender identities in order to prioritize higher education academic requirements. When Latino males are determined to achieve a college degree, they are able to adjust their familism gender role expectations and shift their …

Effect Of Hyperchloremia On Acute Kidney Injury In Critically Ill Septic Patients: A Retrospective Cohort Study, Lenar Yessayan, Javier A. Neyra, Fabrizio Canepa-Escaro, George Vasquez-Rios, Michael Heung, Jerry Yee, Jerry Yee

Nephrology Articles

BACKGROUND: Hyperchloremia is common in critically ill septic patients. The impact of hyperchloremia on the incidence of acute kidney injury (AKI) is not well studied. We investigated the association between hyperchloremia and AKI within the first 72 h of intensive care unit (ICU) admission.

METHODS: 6490 ICU adult patients admitted with severe sepsis or septic shock were screened for eligibility. Exclusion criteria included: AKI on admission, baseline estimated glomerular filtration rate (eGFR)/min/1.73 m

RESULTS: A total of 1045 patients were available for analysis following the implementation of eligibility criteria: 303 (29%) had hyperchloremia (Cl

CONCLUSIONS: Hyperchloremia occurs commonly among critically …

Incidence Of Cognitively Defined Late-Onset Alzheimer's Dementia Subgroups From A Prospective Cohort Study., Paul K Crane, Emily Trittschuh, Shubhabrata Mukherjee, Andrew J Saykin, R Elizabeth Sanders, Eric B Larson, Susan M Mccurry, Wayne Mccormick, J D Bowen, Thomas Grabowski, Mackenzie Moore, Julianna Bauman, Alden L Gross, C Dirk Keene, Thomas D Bird, Laura E Gibbons, Jesse Mez

Articles, Abstracts, and Reports

INTRODUCTION: There may be biologically relevant heterogeneity within typical late-onset Alzheimer's dementia.

METHODS: We analyzed cognitive data from people with incident late-onset Alzheimer's dementia from a prospective cohort study. We determined individual averages across memory, visuospatial functioning, language, and executive functioning. We identified domains with substantial impairments relative to that average. We compared demographic, neuropathology, and genetic findings across groups defined by relative impairments.

RESULTS: During 32,286 person-years of follow-up, 869 people developed Alzheimer's dementia. There were 393 (48%) with no domain with substantial relative impairments. Some participants had isolated relative impairments in memory (148, 18%), visuospatial functioning (117, 14%), …

Nadph Oxidase 5 (Nox5)-Induced Reactive Oxygen Signaling Modulates Normoxic Hif-1Α And P27, Smitha Antony, Guojian Jiang, Yongzhong Wu, Jennifer L Meitzler, Hala R Makhlouf, Diana C Haines, Donna Butcher, Dave S B Hoon, Jiuping Ji, Yiping Zhang, Agnes Juhasz, Jiamo Lu, Han Liu, Iris Dahan, Mariam Konate, Krishnendu K Roy, James H Doroshow

Articles, Abstracts, and Reports

NADPH oxidase 5 (NOX5) generated reactive oxygen species (ROS) have been implicated in signaling cascades that regulate cancer cell proliferation. To evaluate and validate NOX5 expression in human tumors, we screened a broad range of tissue microarrays (TMAs), and report substantial overexpression of NOX5 in malignant melanoma and cancers of the prostate, breast, and ovary. In human UACC-257 melanoma cells that possesses high levels of functional endogenous NOX5, overexpression of NOX5 resulted in enhanced cell growth, increased numbers of BrdU positive cells, and increased γ-H2AX levels. Additionally, NOX5-overexpressing (stable and inducible) UACC-257 cells demonstrated increased normoxic HIF-1α expression and decreased …

Physical Aggressiveness And Gray Matter Deficits In Ventromedial Prefrontal Cortex, David S. Chester, Donald R. Lynam, Richard Milich, C. Nathan Dewall

Psychology Faculty Publications

What causes individuals to hurt others? Since the famous case of Phineas Gage, lesions of the ventromedial prefrontal cortex (VMPFC) have been reliably linked to physically aggressive behavior. However, it is unclear whether naturally-occurring deficits in VMPFC, among normal individuals, might have widespread consequences for aggression. Using voxel based morphometry, we regressed gray matter density from the brains of 138 normal female and male adults onto their dispositional levels of physical aggression, verbal aggression, and sex, simultaneously. Physical, but not verbal, aggression was associated with reduced gray matter volume in the VMPFC and to a lesser extent, frontopolar cortex. Participants …

Cognitive Trajectory Changes Over 20 Years Before Dementia Diagnosis: A Large Cohort Study., Ge Li, Eric B Larson, Jane B Shofer, Paul K Crane, Laura E Gibbons, Wayne Mccormick, J D Bowen, Mary Lou Thompson

Articles, Abstracts, and Reports

BACKGROUND/OBJECTIVES: Longitudinal studies have shown an increase in cognitive decline many years before clinical diagnosis of dementia. We sought to estimate changes, relative to "normal" aging, in the trajectory of scores on a global cognitive function test-the Cognitive Abilities Screening Instrument (CASI).

DESIGN: A prospective cohort study.

SETTING: Community-dwelling members of a U.S. health maintenance organization.

PARTICIPANTS: Individuals aged 65 and older who had no dementia diagnosis at baseline and had at least two visits with valid CASI test score (N = 4,315).

MEASUREMENTS: Average longitudinal trajectories, including changes in trajectory before clinical diagnosis in those who would be diagnosed …

Ecog-Acrin (E4805) Randomized Phase Ii Study To Determine The Effect Of 2 Different Doses Of Aflibercept In Patients With Metastatic Renal Cell Carcinoma, Roberto Pili, Opeyemi Jegede, Michael A. Carducci, Judith Manola, David L. Groteluschen, Leonard L. Appleman, Glenn Liu, James C. Shanks, Shaker R. Dakhil, Janice Dutcher, Robert S. Dipaola

Internal Medicine Faculty Publications

Background—Aflibercept is a recombinantly-produced fusion protein that has potent anti-VEGF activity. We tested whether aflibercept has clinical activity in clear cell renal cell carcinoma (ccRCC). The recommended Phase 2 dose was 4 mg/kg but several patients treated at 1 mg/kg demonstrated prolonged progression-free survival (PFS). We therefore tested both doses in a parallel group randomized trial.

Methods—Eligible patients (pts) had histologically confirmed advanced or metastatic ccRCC and previous treatments including prior exposure to a VEGF RTKI. Patients received aflibercept (either 1 mg/kg or 4 mg/kg) day 1 of a 14-day cycle until progression. Patients randomized to 1 mg/kg …