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6 Association Between American Football Play and Parkinson's Disease: Analysis of the Fox Insight Data Set
- Hannah Bruce, Yorghos Tripodis, Michael McClean, Monica Korell, Caroline M Tanner, Brittany Contreras, Joshua Gottesman, Leslie Kirsch, Yasir Karim, Brett Martin, Joseph Palmisano, Thor D Stein, Jesse Mez, Robert A Stern, Charles H Adler, Chris Nowinski, Ann C McKee, Michael L Alosco
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 415-416
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Objective:
Parkinsonism and Parkinson's disease (PD) have been described as consequences of repetitive head impacts (RHI) from boxing, since 1928. Autopsy studies have shown that RHI from other contact sports can also increase risk for neurodegenerative diseases, including chronic traumatic encephalopathy (CTE) and Lewy bodies. In vivo research on the relationship between American football play and PD is scarce, with small samples, and equivocal findings. This study leveraged the Fox Insight study to evaluate the association between American football and parkinsonism and/or PD Diagnosis and related clinical outcomes.
Participants and Methods:Fox Insight is an online study of people with and without PD who are 18+ years (>50,000 enrolled). Participants complete online questionnaires on motor function, cognitive function, and general health behaviors. Participants self-reported whether they "currently have a diagnosis of Parkinson's disease, or parkinsonism, by a physician or other health care professional." In November 2020, the Boston University Head Impact Exposure Assessment was launched in Fox Insight for large-scale data collection on exposure to RHI from contact sports and other sources. Data used in this abstract were obtained from the Fox Insight database https://foxinsight-info.michaeljfox.org/insight/explore/insight.jsp on 01/06/2022. The sample includes 2018 men who endorsed playing an organized sport. Because only 1.6% of football players were women, analyses are limited to men. Responses to questions regarding history of participation in organized football were examined. Other contact and/or non-contact sports served as the referent group. Outcomes included PD status (absence/presence of parkinsonism or PD) and Penn Parkinson's Daily Activities Questionnaire-15 (PDAQ-15) for assessment of cognitive symptoms. Binary logistic regression tested associations between history and years of football play with PD status, controlling for age, education, current heart disease or diabetes, and family history of PD. Linear regressions, controlling for these variables, were used for the PDAQ-15.
Results:Of the 2018 men (mean age=67.67, SD=9.84; 10, 0.5% Black), 788 (39%) played football (mean years of play=4.29, SD=2.88), including 122 (16.3%) who played youth football, 494 (66.0%) played high school, 128 (17.1%) played college football, and 5 (0.7%) played at the semi-professional or professional level. 1738 (86.1%) reported being diagnosed with parkinsonism/PD, and 707 of these were football players (40.7%). History of playing any level of football was associated with increased odds of having a reported parkinsonism or PD diagnosis (OR=1.52, 95% CI=1.14-2.03, p=0.004). The OR remained similar among those age <69 (sample median age) (OR=1.45, 95% CI=0.97-2.17, p=0.07) and 69+ (OR=1.45, 95% CI=0.95-2.22, p=0.09). Among the football players, there was not a significant association between years of play and PD status (OR=1.09, 95% CI=1.00-1.20, p=0.063). History of football play was not associated with PDAQ-15 scores (n=1980) (beta=-0.78, 95% CI=-1.59-0.03, p=0.059) among the entire sample.
Conclusions:Among 2018 men from a data set enriched for PD, playing organized football was associated with increased odds of having a reported parkinsonism/PD diagnosis. Next steps include examination of the contribution of traumatic brain injury and other sources of RHI (e.g., soccer, military service).
64 Neuroimaging Evidence of Neurodegenerative Disease in Former Professional American Football Players Who “Fail” Validity Testing: A Case Series
- Ranjani Shankar, Julia Culhane, Leonardo Iaccarino, Chris Nowinski, Nidhi Mundada, Karen Smith, Jeremy Tanner, Charles Windon, Yorghos Tripodis, Gustavo Mercier, Thor D Stein, Anne C McKee, Robert A Stern, Neil Kowall, Bruce L Miller, Jesse Mez, Ron Killiany, Gil D Rabinovici, Michael L Alosco, Breton M Asken
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 574-575
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Objective:
Former professional American football players have a high relative risk for neurodegenerative diseases like chronic traumatic encephalopathy (CTE). Interpreting low cognitive test scores in this population occasionally is complicated by performance on validity testing. Neuroimaging biomarkers may help inform whether a neurodegenerative disease is present in these situations. We report three cases of retired professional American football players who completed comprehensive neuropsychological testing, but “failed” performance validity tests, and underwent multimodal neuroimaging (structural MRI, Aß-PET, and tau-PET).
Participants and Methods:Three cases were identified from the Focused Neuroimaging for the Neurodegenerative Disease Chronic Traumatic Encephalopathy (FIND-CTE) study, an ongoing multimodal imaging study of retired National Football League players with complaints of progressive cognitive decline conducted at Boston University and the UCSF Memory and Aging Center. Participants were relatively young (age range 55-65), had 16 or more years of education, and two identified as Black/African American. Raw neuropsychological test scores were converted to demographically-adjusted z-scores. Testing included standalone (Test of Memory Malingering; TOMM) and embedded (reliable digit span, RDS) performance validity measures. Validity cutoffs were TOMM Trial 2 < 45 and RDS < 7. Structural MRIs were interpreted by trained neurologists. Aß-PET with Florbetapir was used to quantify cortical Aß deposition as global Centiloids (0 = mean cortical signal for a young, cognitively normal, Aß negative individual in their 20s, 100 = mean cortical signal for a patient with mild-to-moderate Alzheimer’s disease dementia). Tau-PET was performed with MK-6240 and first quantified as standardized uptake value ratio (SUVR) map. The SUVR map was then converted to a w-score map representing signal intensity relative to a sample of demographically-matched healthy controls.
Results:All performed in the average range on a word reading-based estimate of premorbid intellect. Contribution of Alzheimer’s disease pathology was ruled out in each case based on Centiloids quantifications < 0. All cases scored below cutoff on TOMM Trial 2 (Case #1=43, Case #2=42, Case #3=19) and Case #3 also scored well below RDS cutoff (2). Each case had multiple cognitive scores below expectations (z < -2.0) most consistently in memory, executive function, processing speed domains. For Case #1, MRI revealed mild atrophy in dorsal fronto-parietal and medial temporal lobe (MTL) regions and mild periventricular white matter disease. Tau-PET showed MTL tau burden modestly elevated relative to controls (regional w-score=0.59, 72nd%ile). For Case #2, MRI revealed cortical atrophy, mild hippocampal atrophy, and a microhemorrhage, with no evidence of meaningful tau-PET signal. For Case #3, MRI showed cortical atrophy and severe white matter disease, and tau-PET revealed significantly elevated MTL tau burden relative to controls (w-score=1.90, 97th%ile) as well as focal high signal in the dorsal frontal lobe (overall frontal region w-score=0.64, 74th%ile).
Conclusions:Low scores on performance validity tests complicate the interpretation of the severity of cognitive deficits, but do not negate the presence of true cognitive impairment or an underlying neurodegenerative disease. In the rapidly developing era of biomarkers, neuroimaging tools can supplement neuropsychological testing to help inform whether cognitive or behavioral changes are related to a neurodegenerative disease.
4 Risk Factor and Biomarker Correlates of FLAIR White Matter Hyperintensities in Former American Football Players
- Monica T Ly, Fatima Tuz-Zahra, Yorghos Tripodis, Charles H Adler, Laura J Balcer, Charles Bernick, Elaine Peskind, Megan L Mariani, Rhoda Au, Sarah J Banks, William B Barr, Jennifer V Wethe, Mark W Bondi, Lisa Delano-Wood, Robert C Cantu, Michael J Coleman, David W Dodick, Michael D McClean, Jesse Mez, Joseph N Palmisano, Brett Martin, Kaitlin Hartlage, Alexander P Lin, Inga K Koerte, Jeffrey L Cummings, Eric M Reiman, Martha E Shenton, Robert A Stern, Sylvain Bouix, Michael L Alosco
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 608-610
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Objective:
White matter hyperintensity (WMH) burden is greater, has a frontal-temporal distribution, and is associated with proxies of exposure to repetitive head impacts (RHI) in former American football players. These findings suggest that in the context of RHI, WMH might have unique etiologies that extend beyond those of vascular risk factors and normal aging processes. The objective of this study was to evaluate the correlates of WMH in former elite American football players. We examined markers of amyloid, tau, neurodegeneration, inflammation, axonal injury, and vascular health and their relationships to WMH. A group of age-matched asymptomatic men without a history of RHI was included to determine the specificity of the relationships observed in the former football players.
Participants and Methods:240 male participants aged 45-74 (60 unexposed asymptomatic men, 60 male former college football players, 120 male former professional football players) underwent semi-structured clinical interviews, magnetic resonance imaging (structural T1, T2 FLAIR, and diffusion tensor imaging), and lumbar puncture to collect cerebrospinal fluid (CSF) biomarkers as part of the DIAGNOSE CTE Research Project. Total WMH lesion volumes (TLV) were estimated using the Lesion Prediction Algorithm from the Lesion Segmentation Toolbox. Structural equation modeling, using Full-Information Maximum Likelihood (FIML) to account for missing values, examined the associations between log-TLV and the following variables: total cortical thickness, whole-brain average fractional anisotropy (FA), CSF amyloid ß42, CSF p-tau181, CSF sTREM2 (a marker of microglial activation), CSF neurofilament light (NfL), and the modified Framingham stroke risk profile (rFSRP). Covariates included age, race, education, APOE z4 carrier status, and evaluation site. Bootstrapped 95% confidence intervals assessed statistical significance. Models were performed separately for football players (college and professional players pooled; n=180) and the unexposed men (n=60). Due to differences in sample size, estimates were compared and were considered different if the percent change in the estimates exceeded 10%.
Results:In the former football players (mean age=57.2, 34% Black, 29% APOE e4 carrier), reduced cortical thickness (B=-0.25, 95% CI [0.45, -0.08]), lower average FA (B=-0.27, 95% CI [-0.41, -.12]), higher p-tau181 (B=0.17, 95% CI [0.02, 0.43]), and higher rFSRP score (B=0.27, 95% CI [0.08, 0.42]) were associated with greater log-TLV. Compared to the unexposed men, substantial differences in estimates were observed for rFSRP (Bcontrol=0.02, Bfootball=0.27, 994% difference), average FA (Bcontrol=-0.03, Bfootball=-0.27, 802% difference), and p-tau181 (Bcontrol=-0.31, Bfootball=0.17, -155% difference). In the former football players, rFSRP showed a stronger positive association and average FA showed a stronger negative association with WMH compared to unexposed men. The effect of WMH on cortical thickness was similar between the two groups (Bcontrol=-0.27, Bfootball=-0.25, 7% difference).
Conclusions:These results suggest that the risk factor and biological correlates of WMH differ between former American football players and asymptomatic individuals unexposed to RHI. In addition to vascular risk factors, white matter integrity on DTI showed a stronger relationship with WMH burden in the former football players. FLAIR WMH serves as a promising measure to further investigate the late multifactorial pathologies of RHI.
Genesis of meta-gabbroic crustal xenoliths found in Neogene/Quaternary alkali olivine basalt, northeastern Iran
- Saeed Saadat, Charles R. Stern
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- Journal:
- Geological Magazine / Volume 160 / Issue 2 / February 2023
- Published online by Cambridge University Press:
- 29 September 2022, pp. 260-273
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Rounded to angular granoblastic textured mafic xenoliths, ranging from ∼1 to 6 cm in dimension, occur together with mantle peridotite xenoliths in a small Neogene/Quaternary alkali basalt cone in northeastern Iran. These crustal xenoliths consist of plagioclase feldspar, clinopyroxene, orthopyroxene and minor olivine, spinel, titanomagnetite and apatite. Their bulk compositions are similar to tholeiitic basalts and they are interpreted as meta-gabbroic rocks derived from mid- to lower crustal depths of 18 to 30 km. Rb–Sr dating suggests an age of c. 457 ± 95 Ma for these crustal xenoliths, and their geochemistry shows some similarities to Ordovician gabbros that crop out ∼20 km to the west. The data suggest that the gabbroic proto-lithologies of the xenoliths formed by intrusion of mafic magmas into the mid- to lower crust, possibly during extension and magmatism related to the opening of the Hercynian Palaeotethys ocean that separated central and eastern Iran from the Eurasian plate during the Late Palaeozoic.
Chapter One - Introduction: Merton’s Self-Exemplifying Classical Sociological Contributions
- Edited by Charles Crothers, Lorenzo Sabetta
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- Book:
- The Anthem Companion to Robert K. Merton
- Published by:
- Anthem Press
- Published online:
- 10 January 2023
- Print publication:
- 13 September 2022, pp 1-34
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Summary
This chapter is an introduction to Robert K. Merton's life, work and position in the sociological landscape, and to this Anthem Companion, which explores aspects of these topics in detail. Here, we provide an overall framework within which the various specialist essays can be located.
Over his 70-year career, Merton worked across a wide array of substantive areas including, in chronological order, historical sociology of science, anomie theory and the sociology of deviance, ethnic studies, the sociology of knowledge, the sociology and social predictions (self-fulfilling and suicidal prophecies), housing/community studies, mass media/communication studies, bureaucracy and organizations, the professions and, toward the end of his career, an emerging programme in what he referred to as ‘sociological semantics’. Much this substantive work exhibits a marked discontinuity which is the typical pattern in the growth and development of knowledge – often a substantive concern was put aside, only to be picked up, reworked and extended later in his career.
What did remain constant were his theoretical concerns and modus operandi – while they evolved over time – that centered on analysis of diverse types of social structures, and especially how social structures both enable and constrain – provide incentives for and sanctions against – the social actions that people choose to undertake in their everyday lives. In addition, Merton then examines the consequences – both intended and unintended – of these actions for individuals, groups, organizations, and for society itself.
Throughout his career, Merton coined a slew of sociological concepts and terms, presented in the more than 20 books and 200 scholarly articles that he either authored, co-authored or edited, including ‘unanticipated consequences of social action’, ‘manifest and latent functions’, ‘the self-fulfilling prophecy’, ‘focus groups’, ‘role models’, and ‘the Matthew Effect’, to name but a few. Merton also served in various roles on various learned societies, funding agencies, advisory boards, and federal commissions and advocated for establishing the professional and cognitive identity of the fledgling discipline of sociology.
These contributions varied in quality and consequence and generated a secondary literature comprising a large volume of citations. He is one of the most cited scholars of the twentieth century. His classic Social Theory and Social Structure (STSS) has been cited more than 5,000 times not to mention the uncited influence of his work which has become so well known that it is known in Merton's own phrase as ‘obliterated by incorporation’.
55484 Dual activation of CAR and Nrf2 improves the efficacy: toxicity ratio of cyclophosphamide and doxorubicin-based treatment of TNBC
- Sydney Stern, Dongdong Liang, Linhao Li, Ritika Kurian, Caitlin Lynch, Scott Heyward, Ajoke Kareem, Young Chun, Charles Hong, Fengtian Xue, Hongbing Wang
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- Journal:
- Journal of Clinical and Translational Science / Volume 5 / Issue s1 / March 2021
- Published online by Cambridge University Press:
- 30 March 2021, p. 98
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ABSTRACT IMPACT: Triple negative breast cancer (TNBC) affects 10-20% of women with breast cancer and is biologically more aggressive than other subtypes. The novel compound we have developed, DL7076, would give clinicians a vital strategy to improve the commonly used cyclophosphamide (CPA) and doxorubicin (DOX) regimen in the treatment of TNBC. OBJECTIVES/GOALS: The objective of this research project is to develop a novel compound which can activate both 1) the constitutive androstane receptor (CAR) and subsequently enhance the CYP2B6-mediated activation of CPA, and 2) the nuclear factor erythroid- related factor-2 (Nrf2) leading to the cardiomyocyte protection from DOX-associated cardiotoxicity. METHODS/STUDY POPULATION: Following the identification of the compound candidate, DL7076 was evaluated for tissue specific induction of CAR and Nrf2 using qPCR, western blot analysis, and luciferase reporter assays.
Further, we have developed a multicellular coculture model incorporating human primary hepatocytes for metabolism, TNBC spheroids as the target, and cardiomyocytes as a side target of DOX. We have investigated the anticancer effects of CPA/DOX on TNBC cells and the toxic effects on cardiomyocytes with/without a CAR-Nrf2 activator, in a multicellular environment where hepatic metabolism is well-retained. RESULTS/ANTICIPATED RESULTS: We found that our dual activator of CAR and Nrf2, DL7076, exhibits tissue specific induction of CAR and Nrf2. Inclusion of DL7076 in combination with the CPA/DOX regimen improves anticancer efficacy, through the subsequent increase in the formation of the active CPA metabolite. With the addition of DL7076, DOX-mediated off-target cardiotoxicity was markedly reduced.
Lastly, utilizing the novel coculture system with human primary hepatocytes, TNBC spheroids, and cardiomyocytes, the inclusion of DL7076 to the CPA/DOX regimen shows decreased spheroid viability and improved cardiomyocyte viability and function. DISCUSSION/SIGNIFICANCE OF FINDINGS: Our findings suggest that DL7076 can facilitate DOX/CPA containing regimens by increasing CAR-mediated metabolism and subsequent CPA bioactivation while selectively protecting cardiomyocytes from DOX-induced toxicity. This research is expected to translate our basic scientific findings into therapeutic interventions for women with TNBC.
Las Quemas Rockshelter: Understanding Human Occupations of Andean Forests of Central Patagonia (Aisén, Chile), Southern South America
- César Méndez, Omar Reyes, Amalia Nuevo Delaunay, Héctor Velásquez, Valentina Trejo, Natalie Hormazábal, Marcelo Solari, Charles R. Stern
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- Journal:
- Latin American Antiquity / Volume 27 / Issue 2 / June 2016
- Published online by Cambridge University Press:
- 20 January 2017, pp. 207-226
- Print publication:
- June 2016
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Hunter-gatherer occupations of the forests of Patagonia are still not well understood compared to those of the open steppe and the coasts. The paucity of forest sites with a thorough chronological framework and the incomplete picture of climate-human dynamics in such environments pose a challenge to understanding the occupations of such habitats. This paper presents recent work at the Las Quemas rockshelter, an archaeological site located in the Andean forests of the Aisén region (44°38’ S) dating between 6100 and 2400 cal B.P. We examine the context of the site, its rock art, and the technological and functional dimensions of its lithic assemblage. By comparing these records with local environmental reconstructions that report forest area fluctuations after the Post-Glacial period, this study provides novel data for a comprehensive regional-scale model of human occupations in central Patagonian forests. Following an initial mid-Holocene occupation, recurring occupational events at the site coincide with a significant contraction of forested area in the region during the late Holocene. The results are discussed in regard to regional archaeological data and current models of forest occupation in Patagonia.
Contributors
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- By Mitchell Aboulafia, Frederick Adams, Marilyn McCord Adams, Robert M. Adams, Laird Addis, James W. Allard, David Allison, William P. Alston, Karl Ameriks, C. Anthony Anderson, David Leech Anderson, Lanier Anderson, Roger Ariew, David Armstrong, Denis G. Arnold, E. J. Ashworth, Margaret Atherton, Robin Attfield, Bruce Aune, Edward Wilson Averill, Jody Azzouni, Kent Bach, Andrew Bailey, Lynne Rudder Baker, Thomas R. Baldwin, Jon Barwise, George Bealer, William Bechtel, Lawrence C. Becker, Mark A. Bedau, Ernst Behler, José A. Benardete, Ermanno Bencivenga, Jan Berg, Michael Bergmann, Robert L. Bernasconi, Sven Bernecker, Bernard Berofsky, Rod Bertolet, Charles J. Beyer, Christian Beyer, Joseph Bien, Joseph Bien, Peg Birmingham, Ivan Boh, James Bohman, Daniel Bonevac, Laurence BonJour, William J. Bouwsma, Raymond D. Bradley, Myles Brand, Richard B. Brandt, Michael E. Bratman, Stephen E. Braude, Daniel Breazeale, Angela Breitenbach, Jason Bridges, David O. Brink, Gordon G. Brittan, Justin Broackes, Dan W. Brock, Aaron Bronfman, Jeffrey E. Brower, Bartosz Brozek, Anthony Brueckner, Jeffrey Bub, Lara Buchak, Otavio Bueno, Ann E. Bumpus, Robert W. Burch, John Burgess, Arthur W. Burks, Panayot Butchvarov, Robert E. Butts, Marina Bykova, Patrick Byrne, David Carr, Noël Carroll, Edward S. Casey, Victor Caston, Victor Caston, Albert Casullo, Robert L. Causey, Alan K. L. Chan, Ruth Chang, Deen K. Chatterjee, Andrew Chignell, Roderick M. Chisholm, Kelly J. Clark, E. J. Coffman, Robin Collins, Brian P. Copenhaver, John Corcoran, John Cottingham, Roger Crisp, Frederick J. Crosson, Antonio S. Cua, Phillip D. Cummins, Martin Curd, Adam Cureton, Andrew Cutrofello, Stephen Darwall, Paul Sheldon Davies, Wayne A. Davis, Timothy Joseph Day, Claudio de Almeida, Mario De Caro, Mario De Caro, John Deigh, C. F. Delaney, Daniel C. Dennett, Michael R. DePaul, Michael Detlefsen, Daniel Trent Devereux, Philip E. Devine, John M. Dillon, Martin C. Dillon, Robert DiSalle, Mary Domski, Alan Donagan, Paul Draper, Fred Dretske, Mircea Dumitru, Wilhelm Dupré, Gerald Dworkin, John Earman, Ellery Eells, Catherine Z. Elgin, Berent Enç, Ronald P. Endicott, Edward Erwin, John Etchemendy, C. Stephen Evans, Susan L. Feagin, Solomon Feferman, Richard Feldman, Arthur Fine, Maurice A. Finocchiaro, William FitzPatrick, Richard E. Flathman, Gvozden Flego, Richard Foley, Graeme Forbes, Rainer Forst, Malcolm R. Forster, Daniel Fouke, Patrick Francken, Samuel Freeman, Elizabeth Fricker, Miranda Fricker, Michael Friedman, Michael Fuerstein, Richard A. Fumerton, Alan Gabbey, Pieranna Garavaso, Daniel Garber, Jorge L. A. Garcia, Robert K. Garcia, Don Garrett, Philip Gasper, Gerald Gaus, Berys Gaut, Bernard Gert, Roger F. Gibson, Cody Gilmore, Carl Ginet, Alan H. Goldman, Alvin I. Goldman, Alfonso Gömez-Lobo, Lenn E. Goodman, Robert M. Gordon, Stefan Gosepath, Jorge J. E. Gracia, Daniel W. Graham, George A. Graham, Peter J. Graham, Richard E. Grandy, I. Grattan-Guinness, John Greco, Philip T. Grier, Nicholas Griffin, Nicholas Griffin, David A. Griffiths, Paul J. Griffiths, Stephen R. Grimm, Charles L. Griswold, Charles B. Guignon, Pete A. Y. Gunter, Dimitri Gutas, Gary Gutting, Paul Guyer, Kwame Gyekye, Oscar A. Haac, Raul Hakli, Raul Hakli, Michael Hallett, Edward C. Halper, Jean Hampton, R. James Hankinson, K. R. Hanley, Russell Hardin, Robert M. Harnish, William Harper, David Harrah, Kevin Hart, Ali Hasan, William Hasker, John Haugeland, Roger Hausheer, William Heald, Peter Heath, Richard Heck, John F. Heil, Vincent F. Hendricks, Stephen Hetherington, Francis Heylighen, Kathleen Marie Higgins, Risto Hilpinen, Harold T. Hodes, Joshua Hoffman, Alan Holland, Robert L. Holmes, Richard Holton, Brad W. Hooker, Terence E. Horgan, Tamara Horowitz, Paul Horwich, Vittorio Hösle, Paul Hoβfeld, Daniel Howard-Snyder, Frances Howard-Snyder, Anne Hudson, Deal W. Hudson, Carl A. Huffman, David L. Hull, Patricia Huntington, Thomas Hurka, Paul Hurley, Rosalind Hursthouse, Guillermo Hurtado, Ronald E. Hustwit, Sarah Hutton, Jonathan Jenkins Ichikawa, Harry A. Ide, David Ingram, Philip J. Ivanhoe, Alfred L. Ivry, Frank Jackson, Dale Jacquette, Joseph Jedwab, Richard Jeffrey, David Alan Johnson, Edward Johnson, Mark D. Jordan, Richard Joyce, Hwa Yol Jung, Robert Hillary Kane, Tomis Kapitan, Jacquelyn Ann K. Kegley, James A. Keller, Ralph Kennedy, Sergei Khoruzhii, Jaegwon Kim, Yersu Kim, Nathan L. King, Patricia Kitcher, Peter D. Klein, E. D. Klemke, Virginia Klenk, George L. Kline, Christian Klotz, Simo Knuuttila, Joseph J. Kockelmans, Konstantin Kolenda, Sebastian Tomasz Kołodziejczyk, Isaac Kramnick, Richard Kraut, Fred Kroon, Manfred Kuehn, Steven T. Kuhn, Henry E. Kyburg, John Lachs, Jennifer Lackey, Stephen E. Lahey, Andrea Lavazza, Thomas H. Leahey, Joo Heung Lee, Keith Lehrer, Dorothy Leland, Noah M. Lemos, Ernest LePore, Sarah-Jane Leslie, Isaac Levi, Andrew Levine, Alan E. Lewis, Daniel E. Little, Shu-hsien Liu, Shu-hsien Liu, Alan K. L. Chan, Brian Loar, Lawrence B. Lombard, John Longeway, Dominic McIver Lopes, Michael J. Loux, E. J. Lowe, Steven Luper, Eugene C. Luschei, William G. Lycan, David Lyons, David Macarthur, Danielle Macbeth, Scott MacDonald, Jacob L. Mackey, Louis H. Mackey, Penelope Mackie, Edward H. Madden, Penelope Maddy, G. B. Madison, Bernd Magnus, Pekka Mäkelä, Rudolf A. Makkreel, David Manley, William E. Mann (W.E.M.), Vladimir Marchenkov, Peter Markie, Jean-Pierre Marquis, Ausonio Marras, Mike W. Martin, A. P. Martinich, William L. McBride, David McCabe, Storrs McCall, Hugh J. McCann, Robert N. McCauley, John J. McDermott, Sarah McGrath, Ralph McInerny, Daniel J. McKaughan, Thomas McKay, Michael McKinsey, Brian P. McLaughlin, Ernan McMullin, Anthonie Meijers, Jack W. Meiland, William Jason Melanson, Alfred R. Mele, Joseph R. Mendola, Christopher Menzel, Michael J. Meyer, Christian B. Miller, David W. Miller, Peter Millican, Robert N. Minor, Phillip Mitsis, James A. Montmarquet, Michael S. Moore, Tim Moore, Benjamin Morison, Donald R. Morrison, Stephen J. Morse, Paul K. Moser, Alexander P. D. Mourelatos, Ian Mueller, James Bernard Murphy, Mark C. Murphy, Steven Nadler, Jan Narveson, Alan Nelson, Jerome Neu, Samuel Newlands, Kai Nielsen, Ilkka Niiniluoto, Carlos G. Noreña, Calvin G. Normore, David Fate Norton, Nikolaj Nottelmann, Donald Nute, David S. Oderberg, Steve Odin, Michael O’Rourke, Willard G. Oxtoby, Heinz Paetzold, George S. Pappas, Anthony J. Parel, Lydia Patton, R. P. Peerenboom, Francis Jeffry Pelletier, Adriaan T. Peperzak, Derk Pereboom, Jaroslav Peregrin, Glen Pettigrove, Philip Pettit, Edmund L. Pincoffs, Andrew Pinsent, Robert B. Pippin, Alvin Plantinga, Louis P. Pojman, Richard H. Popkin, John F. Post, Carl J. Posy, William J. Prior, Richard Purtill, Michael Quante, Philip L. Quinn, Philip L. Quinn, Elizabeth S. Radcliffe, Diana Raffman, Gerard Raulet, Stephen L. Read, Andrews Reath, Andrew Reisner, Nicholas Rescher, Henry S. Richardson, Robert C. Richardson, Thomas Ricketts, Wayne D. Riggs, Mark Roberts, Robert C. Roberts, Luke Robinson, Alexander Rosenberg, Gary Rosenkranz, Bernice Glatzer Rosenthal, Adina L. Roskies, William L. Rowe, T. M. Rudavsky, Michael Ruse, Bruce Russell, Lilly-Marlene Russow, Dan Ryder, R. M. Sainsbury, Joseph Salerno, Nathan Salmon, Wesley C. Salmon, Constantine Sandis, David H. Sanford, Marco Santambrogio, David Sapire, Ruth A. Saunders, Geoffrey Sayre-McCord, Charles Sayward, James P. Scanlan, Richard Schacht, Tamar Schapiro, Frederick F. Schmitt, Jerome B. Schneewind, Calvin O. Schrag, Alan D. Schrift, George F. Schumm, Jean-Loup Seban, David N. Sedley, Kenneth Seeskin, Krister Segerberg, Charlene Haddock Seigfried, Dennis M. Senchuk, James F. Sennett, William Lad Sessions, Stewart Shapiro, Tommie Shelby, Donald W. Sherburne, Christopher Shields, Roger A. Shiner, Sydney Shoemaker, Robert K. Shope, Kwong-loi Shun, Wilfried Sieg, A. John Simmons, Robert L. Simon, Marcus G. Singer, Georgette Sinkler, Walter Sinnott-Armstrong, Matti T. Sintonen, Lawrence Sklar, Brian Skyrms, Robert C. Sleigh, Michael Anthony Slote, Hans Sluga, Barry Smith, Michael Smith, Robin Smith, Robert Sokolowski, Robert C. Solomon, Marta Soniewicka, Philip Soper, Ernest Sosa, Nicholas Southwood, Paul Vincent Spade, T. L. S. Sprigge, Eric O. Springsted, George J. Stack, Rebecca Stangl, Jason Stanley, Florian Steinberger, Sören Stenlund, Christopher Stephens, James P. Sterba, Josef Stern, Matthias Steup, M. A. Stewart, Leopold Stubenberg, Edith Dudley Sulla, Frederick Suppe, Jere Paul Surber, David George Sussman, Sigrún Svavarsdóttir, Zeno G. Swijtink, Richard Swinburne, Charles C. Taliaferro, Robert B. Talisse, John Tasioulas, Paul Teller, Larry S. Temkin, Mark Textor, H. S. Thayer, Peter Thielke, Alan Thomas, Amie L. Thomasson, Katherine Thomson-Jones, Joshua C. Thurow, Vzalerie Tiberius, Terrence N. Tice, Paul Tidman, Mark C. Timmons, William Tolhurst, James E. Tomberlin, Rosemarie Tong, Lawrence Torcello, Kelly Trogdon, J. D. Trout, Robert E. Tully, Raimo Tuomela, John Turri, Martin M. Tweedale, Thomas Uebel, Jennifer Uleman, James Van Cleve, Harry van der Linden, Peter van Inwagen, Bryan W. Van Norden, René van Woudenberg, Donald Phillip Verene, Samantha Vice, Thomas Vinci, Donald Wayne Viney, Barbara Von Eckardt, Peter B. M. Vranas, Steven J. Wagner, William J. Wainwright, Paul E. Walker, Robert E. Wall, Craig Walton, Douglas Walton, Eric Watkins, Richard A. Watson, Michael V. Wedin, Rudolph H. Weingartner, Paul Weirich, Paul J. Weithman, Carl Wellman, Howard Wettstein, Samuel C. Wheeler, Stephen A. White, Jennifer Whiting, Edward R. Wierenga, Michael Williams, Fred Wilson, W. Kent Wilson, Kenneth P. Winkler, John F. Wippel, Jan Woleński, Allan B. Wolter, Nicholas P. Wolterstorff, Rega Wood, W. Jay Wood, Paul Woodruff, Alison Wylie, Gideon Yaffe, Takashi Yagisawa, Yutaka Yamamoto, Keith E. Yandell, Xiaomei Yang, Dean Zimmerman, Günter Zoller, Catherine Zuckert, Michael Zuckert, Jack A. Zupko (J.A.Z.)
- Edited by Robert Audi, University of Notre Dame, Indiana
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- Book:
- The Cambridge Dictionary of Philosophy
- Published online:
- 05 August 2015
- Print publication:
- 27 April 2015, pp ix-xxx
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Quantifying Cognitive Reserve in Older Adults by Decomposing Episodic Memory Variance: Replication and Extension
- Laura B. Zahodne, Jennifer J. Manly, Adam M. Brickman, Karen L. Siedlecki, Charles DeCarli, Yaakov Stern
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- Journal:
- Journal of the International Neuropsychological Society / Volume 19 / Issue 8 / September 2013
- Published online by Cambridge University Press:
- 18 July 2013, pp. 854-862
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The theory of cognitive reserve attempts to explain why some individuals are more resilient to age-related brain pathology. Efforts to explore reserve have been hindered by measurement difficulties. Reed et al. (2010) proposed quantifying reserve as residual variance in episodic memory performance that remains after accounting for demographic factors and brain pathology (whole brain, hippocampal, and white matter hyperintensity volumes). This residual variance represents the discrepancy between an individual's predicted and actual memory performance. The goals of the present study were to extend these methods to a larger, community-based sample and to investigate whether the residual reserve variable is explained by age, predicts longitudinal changes in language, and predicts dementia conversion independent of age. Results support this operational measure of reserve. The residual reserve variable was associated with higher reading ability, lower likelihood of meeting criteria for mild cognitive impairment, lower odds of dementia conversion independent of age, and less decline in language abilities over 3 years. Finally, the residual reserve variable moderated the negative impact of memory variance explained by brain pathology on language decline. This method has the potential to facilitate research on the mechanisms of cognitive reserve and the efficacy of interventions designed to impart reserve. (JINS, 2013, 19, 1–9)
Hunter-gatherers, biogeographic barriers and the development of human settlement in Tierra del Fuego
- Flavia Morello, Luis Borrero, Mauricio Massone, Charles Stern, Arleen García-Herbst, Robert McCulloch, Manuel Arroyo-Kalin, Elisa Calás, Jimena Torres, Alfredo Prieto, Ismael Martinez, Gabriel Bahamonde, Pedro Cárdenas
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Tierra del Fuego represents the southernmost limit of human settlement in the Americas. While people may have started to arrive there around 10 500 BP, when it was still connected to the mainland, the main wave of occupation occurred 5000 years later, by which time it had become an island. The co-existence in the area of maritime hunter-gatherers (in canoes) with previous terrestrial occupants pre-echoes the culturally distinctive groups encountered by the first European visitors in the sixteenth century. The study also provides a striking example of interaction across challenging natural barriers.
Contributors
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- By Giustino Albanese, Andrew Amaranto, Brandon H. Backlund, Alexander Baxter, Abraham Berger, Mark Bernstein, Marian E. Betz, Omar Bholat, Suzanne Bigelow, Carl Bonnett, Elizabeth Borock, Christopher B. Colwell, Alasdair Conn, Moira Davenport, David Dreitlein, Aaron Eberhardt, Ugo A. Ezenkwele, Diana Felton, Spiros G. Frangos, John E. Frank, Jonathan S. Gates, Lewis Goldfrank, Pinchas Halpern, Jean Hammel, Kristin E. Harkin, Jason S. Haukoos, E. Parker Hays, Aaron Hexdall, James F. Holmes, Debra Houry, Jennifer Isenhour, Andy Jagoda, John L. Kendall, Erica Kreisman, Nancy Kwon, Eric Legome, Matthew R. Levine, Phillip D. Levy, Charles Little, Marion Machado, Heather Mahoney, Vincent J. Markovchick, Nancy Martin, John Marx, Julie Mayglothling, Ron Medzon, Maurizio A. Miglietta, Elizabeth L. Mitchell, Ernest Moore, Maria E. Moreira, Sassan Naderi, Salvatore Pardo, Sajan Patel, David Peak, Christine Preblick, Niels K. Rathlev, Charles Ray, Phillip L. Rice, Carlo L. Rosen, Peter Rosen, Livia Santiago-Rosado, Tamara A. Scerpella, David Schwartz, Fred Severyn, Kaushal Shah, Lee W. Shockley, Mari Siegel, Matthew Simons, Michael Stern, D. Matthew Sullivan, Carrie D. Tibbles, Knox H. Todd, Shawn Ulrich, Neil Waldman, Kurt Whitaker, Stephen J. Wolf, Daniel Zlogar
- Edited by Eric Legome, Lee W. Shockley
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- Book:
- Trauma
- Published online:
- 07 September 2011
- Print publication:
- 16 June 2011, pp ix-xiv
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- By John A. Barnden, Antal F. Borbely, Brian Bowdle, Cristina Cacciari, Lynne Cameron, Alan Cienki, Seana Coulson, Alice Deignan, Gilles Fauconnier, Charles Forceville, Dedre Gentner, Raymond W. Gibbs,, Rachel Giora, Sam Glucksberg, Mark Johnson, John M. Kennedy, Walter Kintsch, Zoltán Kövecses, George Lakoff, Graham Low, Teenie Matlock, Linda M. McMullen, Cornelia Müller, Rafael Núñez, Elena Semino, Yeshayahu Shen, Dan Sperber, Gerard Steen, Josef Stern, Mark Turner, Deirdre Wilson, Steven L. Winter, Ning Yu, Lawrence M. Zbikowski
- Edited by Raymond W. Gibbs, Jr., University of California, Santa Cruz
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- Book:
- The Cambridge Handbook of Metaphor and Thought
- Published online:
- 05 June 2012
- Print publication:
- 22 September 2008, pp ix-xii
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Long-term effects of high-dose zidovudine treatment on neuropsychological performance in mildly symptomatic HIV-positive patients: Results of a randomized, double-blind, placebo-controlled investigation
- ANTOLIN M. LLORENTE, WILFRED G. VAN GORP, MARTIN J. STERN, LANCE GEORGE, PAUL SATZ, THOMAS D. MARCOTTE, GILBERT M. CALVILLO, CHARLES H. HINKIN
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- Journal:
- Journal of the International Neuropsychological Society / Volume 7 / Issue 1 / January 2001
- Published online by Cambridge University Press:
- 09 February 2001, pp. 27-32
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This study examined the treatment outcome of high-dose (1500 mg/day) zidovudine (AZT) on neuropsychological (NP) functioning (Trailmaking Test A & B, WAIS-R Digit Symbol, and Rey Auditory Verbal Learning Test) across a 12-month period in mildly symptomatic HIV-1 seropositive men (n = 46 at entry) enrolled in a randomized, double-blind, placebo-controlled trial (VA Cooperative Studies Program #298). Neither short-term (0–6 months) nor long-term (0–12 months) AZT administration revealed enhancement in NP performance. The results suggest that, although AZT may afford patients prophylactic benefits, protracted high-dose AZT treatment does not improve NP functioning in mildly symptomatic HIV-positive individuals. (JINS, 2001, 7, 27–32)