42 results on '"Crawford KA"'
Search Results
2. Prediction and Classification of Alzheimer’s Disease Based on Combined Features From Apolipoprotein-E Genotype, Cerebrospinal Fluid, MR, and FDG-PET Imaging Biomarkers
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Yubraj Gupta, Ramesh Kumar Lama, Goo-Rak Kwon, Alzheimer's Disease Neuroimaging Initiative, Michael W. Weiner, Paul Aisen, Michael Weiner, Ronald Petersen, Clifford R. Jack, William Jagust, John Q. Trojanowki, Arthur W. Toga, Laurel Beckett, Robert C. Green, Andrew J. Saykin, John Morris, Leslie M. Shaw, Zaven Khachaturian, Greg Sorensen, Maria Carrillo, Lew Kuller, Marc Raichle, Steven Paul, Peter Davies, Howard Fillit, Franz Hefti, David Holtzman, M. Marcel Mesulam, William Potter, Peter Snyder, Adam Schwartz, Tom Montine, Ronald G. Thomas, Michael Donohue, Sarah Walter, Devon Gessert, Tamie Sather, Gus Jiminez, Archana B. Balasubramanian, Jennifer Mason, Iris Sim, Danielle Harvey, Matthew Bernstein, Nick Fox, Paul Thompson, Norbert Schuff, Charles DeCArli, Bret Borowski, Jeff Gunter, Matt Senjem, Prashanthi Vemuri, David Jones, Kejal Kantarci, Chad Ward, Robert A. Koeppe, Norm Foster, Eric M. Reiman, Kewei Chen, Chet Mathis, Susan Landau, John C. Morris, Nigel J. Cairns, Erin Franklin, Lisa Taylor-Reinwald, Virginia Lee, Magdalena Korecka, Michal Figurski, Karen Crawford, Scott Neu, Tatiana M. Foroud, Steven Potkin, Li Shen, Kelley Faber, Sungeun Kim, Kwangsik Nho, Lean Thal, Leon Thal, Neil Buckholtz, Peter J. Snyder, Marilyn Albert, Richard Frank, John Hsiao, Jeffrey Kaye, Joseph Quinn, Lisa Silbert, Betty Lind, Raina Carter, Sara Dolen, Lon S. Schneider, Sonia Pawluczyk, Mauricio Becerra, Liberty Teodoro, Bryan M. Spann, James Brewer, Helen Vanderswag, Adam Fleisher, Judith L. Heidebrink, Joanne L. Lord, Sara S. Mason, Colleen S. Albers, David Knopman, Kris Johnson, Rachelle S. Doody, Javier Villanueva-Meyer, Valory Pavlik, Victoria Shibley, Munir Chowdhury, Susan Rountree, Mimi Dang, Yaakov Stern, Lawrence S. Honig, Karen L. Bell, Beau Ances, Maria Carroll, Mary L. Creech, Mark A. Mintun, Stacy Schneider, Angela Oliver, Daniel Marson, David Geldmacher, Marissa Natelson Love, Randall Griffith, David Clark, John Brockington, Erik Roberson, Hillel Grossman, Effie Mitsis, Raj C. Shah, Leyla deToledo-Morrell, Ranjan Duara, Maria T. Greig-Custo, Warren Barker, Chiadi Onyike, Daniel D'Agostino, Stephanie Kielb, Martin Sadowski, Mohammed O. Sheikh, Ulysse Anaztasia, Gaikwad Mrunalini, P. Murali Doraiswamy, Jeffrey R. Petrella, Salvador Borges-Neto, Terence Z. Wong, Edward Coleman, Steven E. Arnold, Jason H. Karlawish, David A. Wolk, Christopher M. Clark, Charles D. Smith, Greg Jicha, Peter Hardy, Partha Sinha, Elizabeth Oates, Gary Conrad, Oscar L. Lopez, MaryAnn Oakley, Donna M. Simpson, Anton P. Porsteinsson, Bonnie S. Goldstein, Kim Martin, Kelly M. Makino, M. Saleem Ismail, Connie Brand, Steven G. Potkin, Adrian Preda, Dana Nguyen, Kyle Womack, Dana Mathews, Mary Quiceno, Allan I. Levey, James J. Lah, Janet S. Cellar, Jeffrey M. Burns, Russell H. Swerdlow, William M. Brooks, Liana Apostolova, Kathleen Tingus, Ellen Woo, Daniel H.S. Silverman, Po H. Lu, George Bartzokis, Neill R Graff-Radford, Francine Parfitt, Kim Poki-Walker, Martin R. Farlow, Ann Marie Hake, Brandy R. Matthews, Jared R. Brosch, Scott Herring, Christopher H. van Dyck, Richard E. Carson, Martha G. MacAvoy, Pradeep Varma, Howard Chertkow, Howard Bergman, Chris Hosein, Sandra Black, Bojana Stefanovic, Curtis Caldwell, Ging-Yuek Robin Hsiung, Benita Mudge, Vesna Sossi, Howard Feldman, Michele Assaly, Elizabeth Finger, Stephen Pasternack, Irina Rachisky, Dick Trost, Andrew Kertesz, Charles Bernick, Donna Munic, Marek-Marsel Mesulam, Emily Rogalski, Kristine Lipowski, Sandra Weintraub, Borna Bonakdarpour, Diana Kerwin, Chuang-Kuo Wu, Nancy Johnson, Carl Sadowsky, Teresa Villena, Raymond Scott Turner, Kathleen Johnson, Brigid Reynolds, Reisa A. Sperling, Keith A. Johnson, Gad Marshall, Jerome Yesavage, Joy L. Taylor, Barton Lane, Allyson Rosen, Jared Tinklenberg, Marwan N. Sabbagh, Christine M. Belden, Sandra A. Jacobson, Sherye A. Sirrel, Neil Kowall, Ronald Killiany, Andrew E. Budson, Alexander Norbash, Patricia Lynn Johnson, Thomas O. Obisesan, Saba Wolday, Joanne Allard, Alan Lerner, Paula Ogrocki, Curtis Tatsuoka, Parianne Fatica, Evan Fletcher, Pauline Maillard, John Olichney, Charles DeCarli, Owen Carmichael, Smita Kittur, Michael Borrie, T-Y Lee, Rob Bartha, Sterling Johnson, Sanjay Asthana, Cynthia M. Carlsson, Pierre Tariot, Anna Burke, Ann Marie Milliken, Nadira Trncic, Stephanie Reeder, Vernice Bates, Horacio Capote, Michelle Rainka, Douglas W. Scharre, Maria Kataki, Brendan Kelley, Earl A. Zimmerman, Dzintra Celmins, Alice D. Brown, Godfrey D. Pearlson, Karen Blank, Karen Anderson, Laura A. Flashman, Marc Seltzer, Mary L. Hynes, Robert B. Santulli, Kaycee M. Sink, Gordineer Leslie, Jeff D. Williamson, Pradeep Garg, Franklin Watkins, Brian R. Ott, Geoffrey Tremont, Lori A. Daiello, Stephen Salloway, Paul Malloy, Stephen Correia, Howard J. Rosen, Bruce L. Miller, David Perry, Jacobo Mintzer, Kenneth Spicer, David Bachman, Stephen Pasternak, Irina Rachinsky, John Rogers, Dick Drost, Nunzio Pomara, Raymundo Hernando, Antero Sarrael, Susan K. Schultz, Karen Ekstam Smith, Hristina Koleva, Ki Won Nam, Hyungsub Shim, Norman Relkin, Gloria Chiang, Michael Lin, Lisa Ravdin, Amanda Smith, Balebail Ashok Raj, Kristin Fargher, Thomas Neylan, Jordan Grafman, Gessert Devon, Davis Melissa, Rosemary Morrison, Hayes Jacqueline, Finley Shannon, Kantarci Kejal, Ward Chad, Erin Householder, Crawford Karen, Neu Scott, Friedl Karl, Becerra Mauricio, Debra Fleischman, Konstantinos Arfanakis, Daniel Varon, Maria T Greig, Olga James, Bonnie Goldstein, Kimberly S. Martin, Dino Massoglia, Olga Brawman-Mintzer, Walter Martinez, Howard Rosen, Kelly Behan, Sterling C. Johnson, J. Jay Fruehling, Sandra Harding, Elaine R. Peskind, Eric C. Petrie, Gail Li, Jerome A. Yesavage, Ansgar J. Furst, Steven Chao, Scott Mackin, Rema Raman, Erin Drake, Mike Donohue, Gustavo Jimenez, Kelly Harless, Jennifer Salazar, Yuliana Cabrera, Lindsey Hergesheimer, Elizabeth Shaffer, Craig Nelson, David Bickford, Meryl Butters, Michelle Zmuda, Denise Reyes, Kelley M. Faber, Kelly N. Nudelman, Yiu Ho Au, Kelly Scherer, Daniel Catalinotto, Samuel Stark, Elise Ong, and Dariella Fernandez
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Alzheimer's disease ,MCIs (MCI stable) ,MCIc (MCI converted) ,sMRI ,FDG-PET ,CSF ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
Alzheimer's disease (AD), including its mild cognitive impairment (MCI) phase that may or may not progress into the AD, is the most ordinary form of dementia. It is extremely important to correctly identify patients during the MCI stage because this is the phase where AD may or may not develop. Thus, it is crucial to predict outcomes during this phase. Thus far, many researchers have worked on only using a single modality of a biomarker for the diagnosis of AD or MCI. Although recent studies show that a combination of one or more different biomarkers may provide complementary information for the diagnosis, it also increases the classification accuracy distinguishing between different groups. In this paper, we propose a novel machine learning-based framework to discriminate subjects with AD or MCI utilizing a combination of four different biomarkers: fluorodeoxyglucose positron emission tomography (FDG-PET), structural magnetic resonance imaging (sMRI), cerebrospinal fluid (CSF) protein levels, and Apolipoprotein-E (APOE) genotype. The Alzheimer's Disease Neuroimaging Initiative (ADNI) baseline dataset was used in this study. In total, there were 158 subjects for whom all four modalities of biomarker were available. Of the 158 subjects, 38 subjects were in the AD group, 82 subjects were in MCI groups (including 46 in MCIc [MCI converted; conversion to AD within 24 months of time period], and 36 in MCIs [MCI stable; no conversion to AD within 24 months of time period]), and the remaining 38 subjects were in the healthy control (HC) group. For each image, we extracted 246 regions of interest (as features) using the Brainnetome template image and NiftyReg toolbox, and later we combined these features with three CSF and two APOE genotype features obtained from the ADNI website for each subject using early fusion technique. Here, a different kernel-based multiclass support vector machine (SVM) classifier with a grid-search method was applied. Before passing the obtained features to the classifier, we have used truncated singular value decomposition (Truncated SVD) dimensionality reduction technique to reduce high dimensional features into a lower-dimensional feature. As a result, our combined method achieved an area under the receiver operating characteristic (AU-ROC) curve of 98.33, 93.59, 96.83, 94.64, 96.43, and 95.24% for AD vs. HC, MCIs vs. MCIc, AD vs. MCIs, AD vs. MCIc, HC vs. MCIc, and HC vs. MCIs subjects which are high relative to single modality results and other state-of-the-art approaches. Moreover, combined multimodal methods have improved the classification performance over the unimodal classification.
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- 2019
- Full Text
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3. New Perspective for Non-invasive Brain Stimulation Site Selection in Mild Cognitive Impairment: Based on Meta- and Functional Connectivity Analyses
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Jiao Liu, Binlong Zhang, Georgia Wilson, Jian Kong, the Alzheimer’s Disease Neuroimaging Initiative, Michael W. Weiner, Paul Aisen, Michael Weiner, Ronald Petersen, Clifford R. Jack, William Jagust, John Q. Trojanowki, Arthur W. Toga, Laurel Beckett, Robert C. Green, Andrew J. Saykin, John Morris, Leslie M. Shaw, Zaven Khachaturian, Greg Sorensen, Maria Carrillo, Lew Kuller, Marc Raichle, Steven Paul, Peter Davies, Howard Fillit, Franz Hefti, David Holtzman, M. Marcel Mesulam, William Potter, Peter Snyder, Adam Schwartz, Tom Montine, Ronald G. Thomas, Michael Donohue, Sarah Walter, Devon Gessert, Tamie Sather, Gus Jiminez, Archana B. Balasubramanian, Jennifer Mason, Iris Sim, Danielle Harvey, Matthew Bernstein, Nick Fox, Paul Thompson, Norbert Schuff, Charles DeCArli, Bret Borowski, Jeff Gunter, Matt Senjem, Prashanthi Vemuri, David Jones, Kejal Kantarci, Chad Ward, Robert A. Koeppe, Norm Foster, Eric M. Reiman, Kewei Chen, Chet Mathis, Susan Landau, John C. Morris, Nigel J. Cairns, Erin Franklin, Lisa Taylor-Reinwald, Virginia Lee, Magdalena Korecka, Michal Figurski, Karen Crawford, Scott Neu, Tatiana M. Foroud, Steven Potkin, Li Shen, Kelley Faber, Sungeun Kim, Kwangsik Nho, Lean Thal, Leon Thal, Neil Buckholtz, Peter J. Snyder, Marilyn Albert, Richard Frank, John Hsiao, Jeffrey Kaye, Joseph Quinn, Lisa Silbert, Betty Lind, Raina Carter, Sara Dolen, Lon S. Schneider, Sonia Pawluczyk, Mauricio Becerra, Liberty Teodoro, Bryan M. Spann, James Brewer, Helen Vanderswag, Adam Fleisher, Judith L. Heidebrink, Joanne L. Lord, Sara S. Mason, Colleen S. Albers, David Knopman, Kris Johnson, Rachelle S. Doody, Javier Villanueva-Meyer, Valory Pavlik, Victoria Shibley, Munir Chowdhury, Susan Rountree, Mimi Dang, Yaakov Stern, Lawrence S. Honig, Karen L. Bell, Beau Ances, Maria Carroll, Mary L. Creech, Mark A. Mintun, Stacy Schneider, Angela Oliver, Daniel Marson, David Geldmacher, Marissa Natelson Love, Randall Griffith, David Clark, John Brockington, Erik Roberson, Hillel Grossman, Effie Mitsis, Raj C. Shah, Leyla deToledo-Morrell, Ranjan Duara, Maria T. Greig-Custo, Warren Barker, Chiadi Onyike, Daniel D'Agostino, Stephanie Kielb, Martin Sadowski, Mohammed O. Sheikh, Ulysse Anaztasia, Gaikwad Mrunalini, P. Murali Doraiswamy, Jeffrey R. Petrella, Salvador Borges-Neto, Terence Z. Wong, Edward Coleman, Steven E. Arnold, Jason H. Karlawish, David A. Wolk, Christopher M. Clark, Charles D. Smith, Greg Jicha, Peter Hardy, Partha Sinha, Elizabeth Oates, Gary Conrad, Oscar L. Lopez, MaryAnn Oakley, Donna M. Simpson, Anton P. Porsteinsson, Bonnie S. Goldstein, Kim Martin, Kelly M. Makino, M. Saleem Ismail, Connie Brand, Steven G. Potkin, Adrian Preda, Dana Nguyen, Kyle Womack, Dana Mathews, Mary Quiceno, Allan I. Levey, James J. Lah, Janet S. Cellar, Jeffrey M. Burns, Russell H. Swerdlow, William M. Brooks, Liana Apostolova, Kathleen Tingus, Ellen Woo, Daniel H.S. Silverman, Po H. Lu, George Bartzokis, Neill R Graff-Radford, Francine Parfitt, Kim Poki-Walker, Martin R. Farlow, Ann Marie Hake, Brandy R. Matthews, Jared R. Brosch, Scott Herring, Christopher H. van Dyck, Richard E. Carson, Martha G. MacAvoy, Pradeep Varma, Howard Chertkow, Howard Bergman, Chris Hosein, Sandra Black, Bojana Stefanovic, Curtis Caldwell, Ging-Yuek Robin Hsiung, Benita Mudge, Vesna Sossi, Howard Feldman, Michele Assaly, Elizabeth Finger, Stephen Pasternack, Irina Rachisky, Dick Trost, Andrew Kertesz, Charles Bernick, Donna Munic, Marek-Marsel Mesulam, Emily Rogalski, Kristine Lipowski, Sandra Weintraub, Borna Bonakdarpour, Diana Kerwin, Chuang-Kuo Wu, Nancy Johnson, Carl Sadowsky, Teresa Villena, Raymond Scott Turner, Kathleen Johnson, Brigid Reynolds, Reisa A. Sperling, Keith A. Johnson, Gad Marshall, Jerome Yesavage, Joy L. Taylor, Barton Lane, Allyson Rosen, Jared Tinklenberg, Marwan N. Sabbagh, Christine M. Belden, Sandra A. Jacobson, Sherye A. Sirrel, Neil Kowall, Ronald Killiany, Andrew E. Budson, Alexander Norbash, Patricia Lynn Johnson, Thomas O. Obisesan, Saba Wolday, Joanne Allard, Alan Lerner, Paula Ogrocki, Curtis Tatsuoka, Parianne Fatica, Evan Fletcher, Pauline Maillard, John Olichney, Charles DeCarli, Owen Carmichael, Smita Kittur, Michael Borrie, T-Y Lee, Rob Bartha, Sterling Johnson, Sanjay Asthana, Cynthia M. Carlsson, Pierre Tariot, Anna Burke, Ann Marie Milliken, Nadira Trncic, Stephanie Reeder, Vernice Bates, Horacio Capote, Michelle Rainka, Douglas W. Scharre, Maria Kataki, Brendan Kelley, Earl A. Zimmerman, Dzintra Celmins, Alice D. Brown, Godfrey D. Pearlson, Karen Blank, Karen Anderson, Laura A. Flashman, Marc Seltzer, Mary L. Hynes, Robert B. Santulli, Kaycee M. Sink, Gordineer Leslie, Jeff D. Williamson, Pradeep Garg, Franklin Watkins, Brian R. Ott, Geoffrey Tremont, Lori A. Daiello, Stephen Salloway, Paul Malloy, Stephen Correia, Howard J. Rosen, Bruce L. Miller, David Perry, Jacobo Mintzer, Kenneth Spicer, David Bachman, Stephen Pasternak, Irina Rachinsky, John Rogers, Dick Drost, Nunzio Pomara, Raymundo Hernando, Antero Sarrael, Susan K. Schultz, Karen Ekstam Smith, Hristina Koleva, Ki Won Nam, Hyungsub Shim, Norman Relkin, Gloria Chiang, Michael Lin, Lisa Ravdin, Amanda Smith, Balebail Ashok Raj, Kristin Fargher, Thomas Neylan, Jordan Grafman, Gessert Devon, Davis Melissa, Rosemary Morrison, Hayes Jacqueline, Finley Shannon, Kantarci Kejal, Ward Chad, Erin Householder, Crawford Karen, Neu Scott, Friedl Karl, Becerra Mauricio, Debra Fleischman, Konstantinos Arfanakis, Daniel Varon, Maria T Greig, Olga James, Bonnie Goldstein, Kimberly S. Martin, Dino Massoglia, Olga Brawman-Mintzer, Walter Martinez, Howard Rosen, Kelly Behan, Sterling C. Johnson, J. Jay Fruehling, Sandra Harding, Elaine R. Peskind, Eric C. Petrie, Gail Li, Jerome A. Yesavage, Ansgar J. Furst, and Steven Chao
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mild cognitive impairment ,non-invasive brain stimulation ,stimulation site ,meta-analysis ,resting state functional connectivity ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
BackgroundNon-invasive brain stimulation (NIBS) has been widely used to treat mild cognitive impairment (MCI). However, there exists no consensus on the best stimulation sites.ObjectiveTo explore potential stimulation locations for NIBS treatment in patients with MCI, combining meta- and resting state functional connectivity (rsFC) analyses.MethodsThe meta-analysis was conducted to identify brain regions associated with MCI. Regions of interest (ROIs) were extracted based on this meta-analysis. The rsFC analysis was applied to 45 MCI patients to determine brain surface regions that are functionally connected with the above ROIs.ResultsWe found that the dorsolateral prefrontal cortex (DLPFC) and inferior frontal gyrus (IFG) were the overlapping brain regions between our results and those of previous studies. In addition, we recommend that the temporoparietal junction (including the angular gyrus), which was found in both the meta- and rsFC analysis, should be considered in NIBS treatment of MCI. Furthermore, the bilateral orbital prefrontal gyrus, inferior temporal gyrus, medial superior frontal gyrus, and right inferior occipital gyrus may be potential brain stimulation sites for NIBS treatment of MCI.ConclusionOur results provide several potential sites for NIBS, such as the DLFPC and IFG, and may shed light on the locations of NIBS sites in the treatment of patients with MCI.
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- 2019
- Full Text
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4. Performing Sparse Regularization and Dimension Reduction Simultaneously in Multimodal Data Fusion
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Zhengshi Yang, Xiaowei Zhuang, Christopher Bird, Karthik Sreenivasan, Virendra Mishra, Sarah Banks, Dietmar Cordes, the Alzheimer's Disease Neuroimaging Initiative, Michael W. Weiner, Paul Aisen, Michael Weiner, Ronald Petersen, Clifford R. Jack, William Jagust, John Q. Trojanowki, Arthur W. Toga, Laurel Beckett, Robert C. Green, Andrew J. Saykin, John Morris, Leslie M. Shaw, Zaven Khachaturian, Greg Sorensen, Maria Carrillo, Lew Kuller, Marc Raichle, Steven Paul, Peter Davies, Howard Fillit, Franz Hefti, David Holtzman, M. Marcel Mesulam, William Potter, Peter Snyder, Adam Schwartz, Tom Montine, Ronald G. Thomas, Michael Donohue, Sarah Walter, Devon Gessert, Tamie Sather, Gus Jiminez, Archana B. Balasubramanian, Jennifer Mason, Iris Sim, Danielle Harvey, Matthew Bernstein, Nick Fox, Paul Thompson, Norbert Schuff, Charles DeCArli, Bret Borowski, Jeff Gunter, Matt Senjem, Prashanthi Vemuri, David Jones, Kejal Kantarci, Chad Ward, Robert A. Koeppe, Norm Foster, Eric M. Reiman, Kewei Chen, Chet Mathis, Susan Landau, John C. Morris, Nigel J. Cairns, Erin Franklin, Lisa Taylor-Reinwald, Virginia Lee, Magdalena Korecka, Michal Figurski, Karen Crawford, Scott Neu, Tatiana M. Foroud, Steven Potkin, Li Shen, Kelley Faber, Sungeun Kim, Kwangsik Nho, Lean Thal, Leon Thal, Neil Buckholtz, Peter J. Snyder, Marilyn Albert, Richard Frank, John Hsiao, Jeffrey Kaye, Joseph Quinn, Lisa Silbert, Betty Lind, Raina Carter, Sara Dolen, Lon S. Schneider, Sonia Pawluczyk, Mauricio Becerra, Liberty Teodoro, Bryan M. Spann, James Brewer, Helen Vanderswag, Adam Fleisher, Judith L. Heidebrink, Joanne L. Lord, Sara S. Mason, Colleen S. Albers, David Knopman, Kris Johnson, Rachelle S. Doody, Javier Villanueva-Meyer, Valory Pavlik, Victoria Shibley, Munir Chowdhury, Susan Rountree, Mimi Dang, Yaakov Stern, Lawrence S. Honig, Karen L. Bell, Beau Ances, Maria Carroll, Mary L. Creech, Mark A. Mintun, Stacy Schneider, Angela Oliver, Daniel Marson, David Geldmacher, Marissa Natelson Love, Randall Griffith, David Clark, John Brockington, Erik Roberson, Hillel Grossman, Effie Mitsis, Raj C. Shah, Leyla deToledo-Morrell, Ranjan Duara, Maria T. Greig-Custo, Warren Barker, Chiadi Onyike, Daniel D'Agostino, Stephanie Kielb, Martin Sadowski, Mohammed O. Sheikh, Ulysse Anaztasia, Gaikwad Mrunalini, P. Murali Doraiswamy, Jeffrey R. Petrella, Salvador Borges-Neto, Terence Z. Wong, Edward Coleman, Steven E. Arnold, Jason H. Karlawish, David A. Wolk, Christopher M. Clark, Charles D. Smith, Greg Jicha, Peter Hardy, Partha Sinha, Elizabeth Oates, Gary Conrad, Oscar L. Lopez, MaryAnn Oakley, Donna M. Simpson, Anton P. Porsteinsson, Bonnie S. Goldstein, Kim Martin, Kelly M. Makino, M. Saleem Ismail, Connie Brand, Steven G. Potkin, Adrian Preda, Dana Nguyen, Kyle Womack, Dana Mathews, Mary Quiceno, Allan I. Levey, James J. Lah, Janet S. Cellar, Jeffrey M. Burns, Russell H. Swerdlow, William M. Brooks, Liana Apostolova, Kathleen Tingus, Ellen Woo, Daniel H.S. Silverman, Po H. Lu, George Bartzokis, Neill R Graff-Radford, Francine Parfitt, Kim Poki-Walker, Martin R. Farlow, Ann Marie Hake, Brandy R. Matthews, Jared R. Brosch, Scott Herring, Christopher H. van Dyck, Richard E. Carson, Martha G. MacAvoy, Pradeep Varma, Howard Chertkow, Howard Bergman, Chris Hosein, Sandra Black, Bojana Stefanovic, Curtis Caldwell, Ging-Yuek Robin Hsiung, Benita Mudge, Vesna Sossi, Howard Feldman, Michele Assaly, Elizabeth Finger, Stephen Pasternack, Irina Rachisky, Dick Trost, Andrew Kertesz, Charles Bernick, Donna Munic, Marek-Marsel Mesulam, Emily Rogalski, Kristine Lipowski, Sandra Weintraub, Borna Bonakdarpour, Diana Kerwin, Chuang-Kuo Wu, Nancy Johnson, Carl Sadowsky, Teresa Villena, Raymond Scott Turner, Kathleen Johnson, Brigid Reynolds, Reisa A. Sperling, Keith A. Johnson, Gad Marshall, Jerome Yesavage, Joy L. Taylor, Barton Lane, Allyson Rosen, Jared Tinklenberg, Marwan N. Sabbagh, Christine M. Belden, Sandra A. Jacobson, Sherye A. Sirrel, Neil Kowall, Ronald Killiany, Andrew E. Budson, Alexander Norbash, Patricia Lynn Johnson, Thomas O. Obisesan, Saba Wolday, Joanne Allard, Alan Lerner, Paula Ogrocki, Curtis Tatsuoka, Parianne Fatica, Evan Fletcher, Pauline Maillard, John Olichney, Charles DeCarli, Owen Carmichael, Smita Kittur, Michael Borrie, T-Y Lee, Rob Bartha, Sterling Johnson, Sanjay Asthana, Cynthia M. Carlsson, Pierre Tariot, Anna Burke, Ann Marie Milliken, Nadira Trncic, Stephanie Reeder, Vernice Bates, Horacio Capote, Michelle Rainka, Douglas W. Scharre, Maria Kataki, Brendan Kelley, Earl A. Zimmerman, Dzintra Celmins, Alice D. Brown, Godfrey D. Pearlson, Karen Blank, Karen Anderson, Laura A. Flashman, Marc Seltzer, Mary L. Hynes, Robert B. Santulli, Kaycee M. Sink, Gordineer Leslie, Jeff D. Williamson, Pradeep Garg, Franklin Watkins, Brian R. Ott, Geoffrey Tremont, Lori A. Daiello, Stephen Salloway, Paul Malloy, Stephen Correia, Howard J. Rosen, Bruce L. Miller, David Perry, Jacobo Mintzer, Kenneth Spicer, David Bachman, Stephen Pasternak, Irina Rachinsky, John Rogers, Dick Drost, Nunzio Pomara, Raymundo Hernando, Antero Sarrael, Susan K. Schultz, Karen Ekstam Smith, Hristina Koleva, Ki Won Nam, Hyungsub Shim, Norman Relkin, Gloria Chiang, Michael Lin, Lisa Ravdin, Amanda Smith, Balebail Ashok Raj, Kristin Fargher, Thomas Neylan, Jordan Grafman, Gessert Devon, Davis Melissa, Rosemary Morrison, Hayes Jacqueline, Finley Shannon, Kantarci Kejal, Ward Chad, Erin Householder, Crawford Karen, Neu Scott, Friedl Karl, Becerra Mauricio, Debra Fleischman, Konstantinos Arfanakis, Daniel Varon, Maria T Greig, Olga James, Bonnie Goldstein, Kimberly S. Martin, Dino Massoglia, Olga Brawman-Mintzer, Walter Martinez, Howard Rosen, Kelly Behan, Sterling C. Johnson, J. Jay Fruehling, Sandra Harding, Elaine R. Peskind, Eric C. Petrie, Gail Li, Jerome A. Yesavage, Ansgar J. Furst, Steven Chao, Scott Mackin, Rema Raman, Erin Drake, Mike Donohue, Gustavo Jimenez, Kelly Harless, Jennifer Salazar, Yuliana Cabrera, Lindsey Hergesheimer, Elizabeth Shaffer, Craig Nelson, David Bickford, Meryl Butters, Michelle Zmuda, Denise Reyes, Kelley M. Faber, Kelly N. Nudelman, Yiu Ho Au, Kelly Scherer, Daniel Catalinotto, Samuel Stark, Elise Ong, and Dariella Fernandez
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sparse principal component analysis ,PCA ,canonical correlation analysis ,CCA ,data fusion ,mild cognitive impairment ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
Collecting multiple modalities of neuroimaging data on the same subject is increasingly becoming the norm in clinical practice and research. Fusing multiple modalities to find related patterns is a challenge in neuroimaging analysis. Canonical correlation analysis (CCA) is commonly used as a symmetric data fusion technique to find related patterns among multiple modalities. In CCA-based data fusion, principal component analysis (PCA) is frequently applied as a preprocessing step to reduce data dimension followed by CCA on dimension-reduced data. PCA, however, does not differentiate between informative voxels from non-informative voxels in the dimension reduction step. Sparse PCA (sPCA) extends traditional PCA by adding sparse regularization that assigns zero weights to non-informative voxels. In this study, sPCA is incorporated into CCA-based fusion analysis and applied on neuroimaging data. A cross-validation method is developed and validated to optimize the parameters in sPCA. Different simulations are carried out to evaluate the improvement by introducing sparsity constraint to PCA. Four fusion methods including sPCA+CCA, PCA+CCA, parallel ICA and sparse CCA were applied on structural and functional magnetic resonance imaging data of mild cognitive impairment subjects and normal controls. Our results indicate that sPCA significantly can reduce the impact of non-informative voxels and lead to improved statistical power in uncovering disease-related patterns by a fusion analysis.
- Published
- 2019
- Full Text
- View/download PDF
5. Quantitative 18F-AV1451 Brain Tau PET Imaging in Cognitively Normal Older Adults, Mild Cognitive Impairment, and Alzheimer's Disease Patients
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Qian Zhao, Min Liu, Lingxia Ha, Yun Zhou, Alzheimer's Disease Neuroimaging Initiative, Michael W. Weiner, Paul Aisen, Michael Weiner, Ronald Petersen, Clifford R. Jack, William Jagust, John Q. Trojanowki, Arthur W. Toga, Laurel Beckett, Robert C. Green, Andrew J. Saykin, John Morris, Leslie M. Shaw, Zaven Khachaturian, Greg Sorensen, Maria Carrillo, Lew Kuller, Marc Raichle, Steven Paul, Peter Davies, Howard Fillit, Franz Hefti, David Holtzman, M. Marcel Mesulam, William Potter, Peter Snyder, Adam Schwartz, Tom Montine, Ronald G. Thomas, Michael Donohue, Sarah Walter, Devon Gessert, Tamie Sather, Gus Jiminez, Archana B. Balasubramanian, Jennifer Mason, Iris Sim, Danielle Harvey, Matthew Bernstein, Nick Fox, Paul Thompson, Norbert Schuff, Charles DeCArli, Bret Borowski, Jeff Gunter, Matt Senjem, Prashanthi Vemuri, David Jones, Kejal Kantarci, Chad Ward, Robert A. Koeppe, Norm Foster, Eric M. Reiman, Kewei Chen, Chet Mathis, Susan Landau, John C. Morris, Nigel J. Cairns, Erin Franklin, Lisa Taylor-Reinwald, Virginia Lee, Magdalena Korecka, Michal Figurski, Karen Crawford, Scott Neu, Tatiana M. Foroud, Steven Potkin, Li Shen, Kelley Faber, Sungeun Kim, Kwangsik Nho, Lean Thal, Leon Thal, Neil Buckholtz, Peter J. Snyder, Marilyn Albert, Richard Frank, John Hsiao, Jeffrey Kaye, Joseph Quinn, Lisa Silbert, Betty Lind, Raina Carter, Sara Dolen, Lon S. Schneider, Sonia Pawluczyk, Mauricio Becerra, Liberty Teodoro, Bryan M. Spann, James Brewer, Helen Vanderswag, Adam Fleisher, Judith L. Heidebrink, Joanne L. Lord, Sara S. Mason, Colleen S. Albers, David Knopman, Kris Johnson, Rachelle S. Doody, Javier Villanueva-Meyer, Valory Pavlik, Victoria Shibley, Munir Chowdhury, Susan Rountree, Mimi Dang, Yaakov Stern, Lawrence S. Honig, Karen L. Bell, Beau Ances, Maria Carroll, Mary L. Creech, Mark A. Mintun, Stacy Schneider, Angela Oliver, Daniel Marson, David Geldmacher, Marissa Natelson Love, Randall Griffith, David Clark, John Brockington, Erik Roberson, Hillel Grossman, Effie Mitsis, Raj C. Shah, Leyla deToledo-Morrell, Ranjan Duara, Maria T. Greig-Custo, Warren Barker, Chiadi Onyike, Daniel D'Agostino, Stephanie Kielb, Martin Sadowski, Mohammed O. Sheikh, Ulysse Anaztasia, Gaikwad Mrunalini, P. Murali Doraiswamy, Jeffrey R. Petrella, Salvador Borges-Neto, Terence Z. Wong, Edward Coleman, Steven E. Arnold, Jason H. Karlawish, David A. Wolk, Christopher M. Clark, Charles D. Smith, Greg Jicha, Peter Hardy, Partha Sinha, Elizabeth Oates, Gary Conrad, Oscar L. Lopez, MaryAnn Oakley, Donna M. Simpson, Anton P. Porsteinsson, Bonnie S. Goldstein, Kim Martin, Kelly M. Makino, M. Saleem Ismail, Connie Brand, Steven G. Potkin, Adrian Preda, Dana Nguyen, Kyle Womack, Dana Mathews, Mary Quiceno, Allan I. Levey, James J. Lah, Janet S. Cellar, Jeffrey M. Burns, Russell H. Swerdlow, William M. Brooks, Liana Apostolova, Kathleen Tingus, Ellen Woo, Daniel H.S. Silverman, Po H. Lu, George Bartzokis, Neill R Graff-Radford, Francine Parfitt, Kim Poki-Walker, Martin R. Farlow, Ann Marie Hake, Brandy R. Matthews, Jared R. Brosch, Scott Herring, Christopher H. van Dyck, Richard E. Carson, Martha G. MacAvoy, Pradeep Varma, Howard Chertkow, Howard Bergman, Chris Hosein, Sandra Black, Bojana Stefanovic, Curtis Caldwell, Ging-Yuek Robin Hsiung, Benita Mudge, Vesna Sossi, Howard Feldman, Michele Assaly, Elizabeth Finger, Stephen Pasternack, Irina Rachisky, Dick Trost, Andrew Kertesz, Charles Bernick, Donna Munic, Marek-Marsel Mesulam, Emily Rogalski, Kristine Lipowski, Sandra Weintraub, Borna Bonakdarpour, Diana Kerwin, Chuang-Kuo Wu, Nancy Johnson, Carl Sadowsky, Teresa Villena, Raymond Scott Turner, Kathleen Johnson, Brigid Reynolds, Reisa A. Sperling, Keith A. Johnson, Gad Marshall, Jerome Yesavage, Joy L. Taylor, Barton Lane, Allyson Rosen, Jared Tinklenberg, Marwan N. Sabbagh, Christine M. Belden, Sandra A. Jacobson, Sherye A. Sirrel, Neil Kowall, Ronald Killiany, Andrew E. Budson, Alexander Norbash, Patricia Lynn Johnson, Thomas O. Obisesan, Saba Wolday, Joanne Allard, Alan Lerner, Paula Ogrocki, Curtis Tatsuoka, Parianne Fatica, Evan Fletcher, Pauline Maillard, John Olichney, Charles DeCarli, Owen Carmichael, Smita Kittur, Michael Borrie, T-Y Lee, Rob Bartha, Sterling Johnson, Sanjay Asthana, Cynthia M. Carlsson, Pierre Tariot, Anna Burke, Ann Marie Milliken, Nadira Trncic, Stephanie Reeder, Vernice Bates, Horacio Capote, Michelle Rainka, Douglas W. Scharre, Maria Kataki, Brendan Kelley, Earl A. Zimmerman, Dzintra Celmins, Alice D. Brown, Godfrey D. Pearlson, Karen Blank, Karen Anderson, Laura A. Flashman, Marc Seltzer, Mary L. Hynes, Robert B. Santulli, Kaycee M. Sink, Gordineer Leslie, Jeff D. Williamson, Pradeep Garg, Franklin Watkins, Brian R. Ott, Geoffrey Tremont, Lori A. Daiello, Stephen Salloway, Paul Malloy, Stephen Correia, Howard J. Rosen, Bruce L. Miller, David Perry, Jacobo Mintzer, Kenneth Spicer, David Bachman, Stephen Pasternak, Irina Rachinsky, John Rogers, Dick Drost, Nunzio Pomara, Raymundo Hernando, Antero Sarrael, Susan K. Schultz, Karen Ekstam Smith, Hristina Koleva, Ki Won Nam, Hyungsub Shim, Norman Relkin, Gloria Chiang, Michael Lin, Lisa Ravdin, Amanda Smith, Balebail Ashok Raj, Kristin Fargher, Thomas Neylan, Jordan Grafman, Gessert Devon, Davis Melissa, Rosemary Morrison, Hayes Jacqueline, Finley Shannon, Kantarci Kejal, Ward Chad, Erin Householder, Crawford Karen, Neu Scott, Friedl Karl, Becerra Mauricio, Debra Fleischman, Konstantinos Arfanakis, Daniel Varon, Maria T Greig, Olga James, Bonnie Goldstein, Kimberly S. Martin, Dino Massoglia, Olga Brawman-Mintzer, Walter Martinez, Howard Rosen, Kelly Behan, Sterling C. Johnson, J. Jay Fruehling, Sandra Harding, Elaine R. Peskind, Eric C. Petrie, Gail Li, Jerome A. Yesavage, Ansgar J. Furst, Steven Chao, Scott Mackin, Rema Raman, Erin Drake, Mike Donohue, Gustavo Jimenez, Kelly Harless, Jennifer Salazar, Yuliana Cabrera, Lindsey Hergesheimer, Elizabeth Shaffer, Craig Nelson, David Bickford, Meryl Butters, Michelle Zmuda, Denise Reyes, Kelley M. Faber, Kelly N. Nudelman, Yiu Ho Au, Kelly Scherer, Daniel Catalinotto, Samuel Stark, Elise Ong, and Dariella Fernandez
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18F-AV1451 ,Tau PET ,cognitively normal ,mild cognition impairment ,Alzheimer's disease ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Recent developments of tau Positron Emission Tomography (PET) allows assessment of regional neurofibrillary tangles (NFTs) deposition in human brain. Among the tau PET molecular probes, 18F-AV1451 is characterized by high selectivity for pathologic tau aggregates over amyloid plaques, limited non-specific binding in white and gray matter, and confined off-target binding. The objectives of the study are (1) to quantitatively characterize regional brain tau deposition measured by 18F-AV1451 PET in cognitively normal older adults (CN), mild cognitive impairment (MCI), and AD participants; (2) to evaluate the correlations between cerebrospinal fluid (CSF) biomarkers or Mini-Mental State Examination (MMSE) and 18F-AV1451 PET standardized uptake value ratio (SUVR); and (3) to evaluate the partial volume effects on 18F-AV1451 brain uptake.Methods: The study included total 115 participants (CN = 49, MCI = 58, and AD = 8) from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Preprocessed 18F-AV1451 PET images, structural MRIs, and demographic and clinical assessments were downloaded from the ADNI database. A reblurred Van Cittertiteration method was used for voxelwise partial volume correction (PVC) on PET images. Structural MRIs were used for PET spatial normalization and region of interest (ROI) definition in standard space. The parametric images of 18F-AV1451 SUVR relative to cerebellum were calculated. The ROI SUVR measurements from PVC and non-PVC SUVR images were compared. The correlation between ROI 18F-AV1451 SUVR and the measurements of MMSE, CSF total tau (t-tau), and phosphorylated tau (p-tau) were also assessed.Results:18F-AV1451 prominently specific binding was found in the amygdala, entorhinal cortex, parahippocampus, fusiform, posterior cingulate, temporal, parietal, and frontal brain regions. Most regional SUVRs showed significantly higher uptake of 18F-AV1451 in AD than MCI and CN participants. SUVRs of small regions like amygdala, entorhinal cortex and parahippocampus were statistically improved by PVC in all groups (p < 0.01). Although there was an increasing tendency of 18F-AV-1451 SUVRs in MCI group compared with CN group, no significant difference of 18F-AV1451 deposition was found between CN and MCI brains with or without PVC (p > 0.05). Declined MMSE score was observed with increasing 18F-AV1451 binding in amygdala, entorhinal cortex, parahippocampus, and fusiform. CSF p-tau was positively correlated with 18F-AV1451 deposition. PVC improved the results of 18F-AV-1451 tau deposition and correlation studies in small brain regions.Conclusion: The typical deposition of 18F-AV1451 tau PET imaging in AD brain was found in amygdala, entorhinal cortex, fusiform and parahippocampus, and these regions were strongly associated with cognitive impairment and CSF biomarkers. Although more deposition was observed in MCI group, the 18F-AV-1451 PET imaging could not differentiate the MCI patients from CN population. More tau deposition related to decreased MMSE score and increased level of CSF p-tau, especially in ROIs of amygdala, entorhinal cortex and parahippocampus. PVC did improve the results of tau deposition and correlation studies in small brain regions and suggest to be routinely used in 18F-AV1451 tau PET quantification.
- Published
- 2019
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6. Corrigendum: Conversion Discriminative Analysis on Mild Cognitive Impairment Using Multiple Cortical Features from MR Images
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Shengwen Guo, Chunren Lai, Congling Wu, Guiyin Cen, The Alzheimer's Disease Neuroimaging Initiative, Michael W. Weiner, Paul Aisen, Michael Weiner, Ronald Petersen, Clifford R. Jack, William Jagust, John Q. Trojanowki, Arthur W. Toga, Laurel Beckett, Robert C. Green, Andrew J. Saykin, John Morris, Leslie M. Shaw, Zaven Khachaturian, Greg Sorensen, Maria Carrillo, Lew Kuller, Marc Raichle, Steven Paul, Peter Davies, Howard Fillit, Franz Hefti, David Holtzman, M. Marcel Mesulam, William Potter, Peter Snyder, Adam Schwartz, Tom Montine, Ronald G. Thomas, Michael Donohue, Sarah Walter, Devon Gessert, Tamie Sather, Gus Jiminez, Archana B. Balasubramanian, Jennifer Mason, Iris Sim, Danielle Harvey, Matthew Bernstein, Nick Fox, Paul Thompson, Norbert Schuff, Charles DeCArli, Bret Borowski, Jeff Gunter, Matt Senjem, Prashanthi Vemuri, David Jones, Kejal Kantarci, Chad Ward, Robert A. Koeppe, Norm Foster, Eric M. Reiman, Kewei Chen, Chet Mathis, Susan Landau, John C. Morris, Nigel J. Cairns, Erin Franklin, Lisa Taylor-Reinwald, Virginia Lee, Magdalena Korecka, Michal Figurski, Karen Crawford, Scott Neu, Tatiana M. Foroud, Steven Potkin, Li Shen, Kelley Faber, Sungeun Kim, Kwangsik Nho, Lean Thal, Leon Thal, Neil Buckholtz, Peter J. Snyder, Marilyn Albert, Richard Frank, John Hsiao, Jeffrey Kaye, Joseph Quinn, Lisa Silbert, Betty Lind, Raina Carter, Sara Dolen, Lon S. Schneider, Sonia Pawluczyk, Mauricio Becerra, Liberty Teodoro, Bryan M. Spann, James Brewer, Helen Vanderswag, Adam Fleisher, Judith L. Heidebrink, Joanne L. Lord, Sara S. Mason, Colleen S. Albers, David Knopman, Kris Johnson, Rachelle S. Doody, Javier Villanueva-Meyer, Valory Pavlik, Victoria Shibley, Munir Chowdhury, Susan Rountree, Mimi Dang, Yaakov Stern, Lawrence S. Honig, Karen L. Bell, Beau Ances, Maria Carroll, Mary L. Creech, Mark A. Mintun, Stacy Schneider, Angela Oliver, Daniel Marson, David Geldmacher, Marissa Natelson Love, Randall Griffith, David Clark, John Brockington, Erik Roberson, Hillel Grossman, Effie Mitsis, Raj C. Shah, Leyla deToledo-Morrell, Ranjan Duara, Maria T. Greig-Custo, Warren Barker, Chiadi Onyike, Daniel D'Agostino, Stephanie Kielb, Martin Sadowski, Mohammed O. Sheikh, Ulysse Anaztasia, Gaikwad Mrunalini, P. Murali Doraiswamy, Jeffrey R. Petrella, Salvador Borges-Neto, Terence Z. Wong, Edward Coleman, Steven E. Arnold, Jason H. Karlawish, David A. Wolk, Christopher M. Clark, Charles D. Smith, Greg Jicha, Peter Hardy, Partha Sinha, Elizabeth Oates, Gary Conrad, Oscar L. Lopez, MaryAnn Oakley, Donna M. Simpson, Anton P. Porsteinsson, Bonnie S. Goldstein, Kim Martin, Kelly M. Makino, M. Saleem Ismail, Connie Brand, Steven G. Potkin, Adrian Preda, Dana Nguyen, Kyle Womack, Dana Mathews, Mary Quiceno, Allan I. Levey, James J. Lah, Janet S. Cellar, Jeffrey M. Burns, Russell H. Swerdlow, William M. Brooks, Liana Apostolova, Kathleen Tingus, Ellen Woo, Daniel H.S. Silverman, Po H. Lu, George Bartzokis, Neill R Graff-Radford, Francine Parfitt, Kim Poki-Walker, Martin R. Farlow, Ann Marie Hake, Brandy R. Matthews, Jared R. Brosch, Scott Herring, Christopher H. van Dyck, Richard E. Carson, Martha G. MacAvoy, Pradeep Varma, Howard Chertkow, Howard Bergman, Chris Hosein, Sandra Black, Bojana Stefanovic, Curtis Caldwell, Ging-Yuek Robin Hsiung, Benita Mudge, Vesna Sossi, Howard Feldman, Michele Assaly, Elizabeth Finger, Stephen Pasternack, Irina Rachisky, Dick Trost, Andrew Kertesz, Charles Bernick, Donna Munic, Marek-Marsel Mesulam, Emily Rogalski, Kristine Lipowski, Sandra Weintraub, Borna Bonakdarpour, Diana Kerwin, Chuang-Kuo Wu, Nancy Johnson, Carl Sadowsky, Teresa Villena, Raymond Scott Turner, Kathleen Johnson, Brigid Reynolds, Reisa A. Sperling, Keith A. Johnson, Gad Marshall, Jerome Yesavage, Joy L. Taylor, Barton Lane, Allyson Rosen, Jared Tinklenberg, Marwan N. Sabbagh, Christine M. Belden, Sandra A. Jacobson, Sherye A. Sirrel, Neil Kowall, Ronald Killiany, Andrew E. Budson, Alexander Norbash, Patricia Lynn Johnson, Thomas O. Obisesan, Saba Wolday, Joanne Allard, Alan Lerner, Paula Ogrocki, Curtis Tatsuoka, Parianne Fatica, Evan Fletcher, Pauline Maillard, John Olichney, Charles DeCarli, Owen Carmichael, Smita Kittur, Michael Borrie, T-Y Lee, Rob Bartha, Sterling Johnson, Sanjay Asthana, Cynthia M. Carlsson, Pierre Tariot, Anna Burke, Ann Marie Milliken, Nadira Trncic, Stephanie Reeder, Vernice Bates, Horacio Capote, Michelle Rainka, Douglas W. Scharre, Maria Kataki, Brendan Kelley, Earl A. Zimmerman, Dzintra Celmins, Alice D. Brown, Godfrey D. Pearlson, Karen Blank, Karen Anderson, Laura A. Flashman, Marc Seltzer, Mary L. Hynes, Robert B. Santulli, Kaycee M. Sink, Gordineer Leslie, Jeff D. Williamson, Pradeep Garg, Franklin Watkins, Brian R. Ott, Geoffrey Tremont, Lori A. Daiello, Stephen Salloway, Paul Malloy, Stephen Correia, Howard J. Rosen, Bruce L. Miller, David Perry, Jacobo Mintzer, Kenneth Spicer, David Bachman, Stephen Pasternak, Irina Rachinsky, John Rogers, Dick Drost, Nunzio Pomara, Raymundo Hernando, Antero Sarrael, Susan K. Schultz, Karen Ekstam Smith, Hristina Koleva, Ki Won Nam, Hyungsub Shim, Norman Relkin, Gloria Chiang, Michael Lin, Lisa Ravdin, Amanda Smith, Balebail Ashok Raj, Kristin Fargher, Thomas Neylan, Jordan Grafman, Gessert Devon, Davis Melissa, Rosemary Morrison, Hayes Jacqueline, Finley Shannon, Kantarci Kejal, Ward Chad, Erin Householder, Crawford Karen, Neu Scott, Friedl Karl, Becerra Mauricio, Debra Fleischman, Konstantinos Arfanakis, Daniel Varon, Maria T Greig, Olga James, Bonnie Goldstein, Kimberly S. Martin, Dino Massoglia, Olga Brawman-Mintzer, Walter Martinez, Howard Rosen, Kelly Behan, Sterling C. Johnson, J. Jay Fruehling, Sandra Harding, Elaine R. Peskind, Eric C. Petrie, Gail Li, Jerome A. Yesavage, Ansgar J. Furst, and Steven Chao
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mild cognitive impairment ,conversion ,cortical feature ,sparse-constrained regression ,feature reduction ,classification ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Published
- 2017
- Full Text
- View/download PDF
7. Conversion Discriminative Analysis on Mild Cognitive Impairment Using Multiple Cortical Features from MR Images
- Author
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Shengwen Guo, Chunren Lai, Congling Wu, Guiyin Cen, The Alzheimer's Disease Neuroimaging Initiative, Michael W. Weiner, Paul Aisen, Michael Weiner, Ronald Petersen, Clifford R. Jack, William Jagust, John Q. Trojanowki, Arthur W. Toga, Laurel Beckett, Robert C. Green, Andrew J. Saykin, John Morris, Leslie M. Shaw, Zaven Khachaturian, Greg Sorensen, Maria Carrillo, Lew Kuller, Marc Raichle, Steven Paul, Peter Davies, Howard Fillit, Franz Hefti, David Holtzman, M. Marcel Mesulam, William Potter, Peter Snyder, Adam Schwartz, Tom Montine, Ronald G. Thomas, Michael Donohue, Sarah Walter, Devon Gessert, Tamie Sather, Gus Jiminez, Archana B. Balasubramanian, Jennifer Mason, Iris Sim, Danielle Harvey, Matthew Bernstein, Nick Fox, Paul Thompson, Norbert Schuff, Charles DeCArli, Bret Borowski, Jeff Gunter, Matt Senjem, Prashanthi Vemuri, David Jones, Kejal Kantarci, Chad Ward, Robert A. Koeppe, Norm Foster, Eric M. Reiman, Kewei Chen, Chet Mathis, Susan Landau, John C. Morris, Nigel J. Cairns, Erin Franklin, Lisa Taylor-Reinwald, Virginia Lee, Magdalena Korecka, Michal Figurski, Karen Crawford, Scott Neu, Tatiana M. Foroud, Steven Potkin, Li Shen, Kelley Faber, Sungeun Kim, Kwangsik Nho, Lean Thal, Leon Thal, Neil Buckholtz, Peter J. Snyder, Marilyn Albert, Richard Frank, John Hsiao, Jeffrey Kaye, Joseph Quinn, Lisa Silbert, Betty Lind, Raina Carter, Sara Dolen, Lon S. Schneider, Sonia Pawluczyk, Mauricio Becerra, Liberty Teodoro, Bryan M. Spann, James Brewer, Helen Vanderswag, Adam Fleisher, Judith L. Heidebrink, Joanne L. Lord, Sara S. Mason, Colleen S. Albers, David Knopman, Kris Johnson, Rachelle S. Doody, Javier Villanueva-Meyer, Valory Pavlik, Victoria Shibley, Munir Chowdhury, Susan Rountree, Mimi Dang, Yaakov Stern, Lawrence S. Honig, Karen L. Bell, Beau Ances, Maria Carroll, Mary L. Creech, Mark A. Mintun, Stacy Schneider, Angela Oliver, Daniel Marson, David Geldmacher, Marissa Natelson Love, Randall Griffith, David Clark, John Brockington, Erik Roberson, Hillel Grossman, Effie Mitsis, Raj C. Shah, Leyla deToledo-Morrell, Ranjan Duara, Maria T. Greig-Custo, Warren Barker, Chiadi Onyike, Daniel D'Agostino, Stephanie Kielb, Martin Sadowski, Mohammed O. Sheikh, Ulysse Anaztasia, Gaikwad Mrunalini, P. Murali Doraiswamy, Jeffrey R. Petrella, Salvador Borges-Neto, Terence Z. Wong, Edward Coleman, Steven E. Arnold, Jason H. Karlawish, David A. Wolk, Christopher M. Clark, Charles D. Smith, Greg Jicha, Peter Hardy, Partha Sinha, Elizabeth Oates, Gary Conrad, Oscar L. Lopez, MaryAnn Oakley, Donna M. Simpson, Anton P. Porsteinsson, Bonnie S. Goldstein, Kim Martin, Kelly M. Makino, M. Saleem Ismail, Connie Brand, Steven G. Potkin, Adrian Preda, Dana Nguyen, Kyle Womack, Dana Mathews, Mary Quiceno, Allan I. Levey, James J. Lah, Janet S. Cellar, Jeffrey M. Burns, Russell H. Swerdlow, William M. Brooks, Liana Apostolova, Kathleen Tingus, Ellen Woo, Daniel H.S. Silverman, Po H. Lu, George Bartzokis, Neill R Graff-Radford, Francine Parfitt, Kim Poki-Walker, Martin R. Farlow, Ann Marie Hake, Brandy R. Matthews, Jared R. Brosch, Scott Herring, Christopher H. van Dyck, Richard E. Carson, Martha G. MacAvoy, Pradeep Varma, Howard Chertkow, Howard Bergman, Chris Hosein, Sandra Black, Bojana Stefanovic, Curtis Caldwell, Ging-Yuek Robin Hsiung, Benita Mudge, Vesna Sossi, Howard Feldman, Michele Assaly, Elizabeth Finger, Stephen Pasternack, Irina Rachisky, Dick Trost, Andrew Kertesz, Charles Bernick, Donna Munic, Marek-Marsel Mesulam, Emily Rogalski, Kristine Lipowski, Sandra Weintraub, Borna Bonakdarpour, Diana Kerwin, Chuang-Kuo Wu, Nancy Johnson, Carl Sadowsky, Teresa Villena, Raymond Scott Turner, Kathleen Johnson, Brigid Reynolds, Reisa A. Sperling, Keith A. Johnson, Gad Marshall, Jerome Yesavage, Joy L. Taylor, Barton Lane, Allyson Rosen, Jared Tinklenberg, Marwan N. Sabbagh, Christine M. Belden, Sandra A. Jacobson, Sherye A. Sirrel, Neil Kowall, Ronald Killiany, Andrew E. Budson, Alexander Norbash, Patricia Lynn Johnson, Thomas O. Obisesan, Saba Wolday, Joanne Allard, Alan Lerner, Paula Ogrocki, Curtis Tatsuoka, Parianne Fatica, Evan Fletcher, Pauline Maillard, John Olichney, Charles DeCarli, Owen Carmichael, Smita Kittur, Michael Borrie, T-Y Lee, Rob Bartha, Sterling Johnson, Sanjay Asthana, Cynthia M. Carlsson, Pierre Tariot, Anna Burke, Ann Marie Milliken, Nadira Trncic, Stephanie Reeder, Vernice Bates, Horacio Capote, Michelle Rainka, Douglas W. Scharre, Maria Kataki, Brendan Kelley, Earl A. Zimmerman, Dzintra Celmins, Alice D. Brown, Godfrey D. Pearlson, Karen Blank, Karen Anderson, Laura A. Flashman, Marc Seltzer, Mary L. Hynes, Robert B. Santulli, Kaycee M. Sink, Gordineer Leslie, Jeff D. Williamson, Pradeep Garg, Franklin Watkins, Brian R. Ott, Geoffrey Tremont, Lori A. Daiello, Stephen Salloway, Paul Malloy, Stephen Correia, Howard J. Rosen, Bruce L. Miller, David Perry, Jacobo Mintzer, Kenneth Spicer, David Bachman, Stephen Pasternak, Irina Rachinsky, John Rogers, Dick Drost, Nunzio Pomara, Raymundo Hernando, Antero Sarrael, Susan K. Schultz, Karen Ekstam Smith, Hristina Koleva, Ki Won Nam, Hyungsub Shim, Norman Relkin, Gloria Chiang, Michael Lin, Lisa Ravdin, Amanda Smith, Balebail Ashok Raj, Kristin Fargher, Thomas Neylan, Jordan Grafman, Gessert Devon, Davis Melissa, Rosemary Morrison, Hayes Jacqueline, Finley Shannon, Kantarci Kejal, Ward Chad, Erin Householder, Crawford Karen, Neu Scott, Friedl Karl, Becerra Mauricio, Debra Fleischman, Konstantinos Arfanakis, Daniel Varon, Maria T Greig, Olga James, Bonnie Goldstein, Kimberly S. Martin, Dino Massoglia, Olga Brawman-Mintzer, Walter Martinez, Howard Rosen, Kelly Behan, Sterling C. Johnson, J. Jay Fruehling, Sandra Harding, Elaine R. Peskind, Eric C. Petrie, Gail Li, Jerome A. Yesavage, Ansgar J. Furst, and Steven Chao
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mild cognitive impairment ,conversion ,cortical feature ,sparse-constrained regression ,feature reduction ,classification ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
Neuroimaging measurements derived from magnetic resonance imaging provide important information required for detecting changes related to the progression of mild cognitive impairment (MCI). Cortical features and changes play a crucial role in revealing unique anatomical patterns of brain regions, and further differentiate MCI patients from normal states. Four cortical features, namely, gray matter volume, cortical thickness, surface area, and mean curvature, were explored for discriminative analysis among three groups including the stable MCI (sMCI), the converted MCI (cMCI), and the normal control (NC) groups. In this study, 158 subjects (72 NC, 46 sMCI, and 40 cMCI) were selected from the Alzheimer's Disease Neuroimaging Initiative. A sparse-constrained regression model based on the l2-1-norm was introduced to reduce the feature dimensionality and retrieve essential features for the discrimination of the three groups by using a support vector machine (SVM). An optimized strategy of feature addition based on the weight of each feature was adopted for the SVM classifier in order to achieve the best classification performance. The baseline cortical features combined with the longitudinal measurements for 2 years of follow-up data yielded prominent classification results. In particular, the cortical thickness produced a classification with 98.84% accuracy, 97.5% sensitivity, and 100% specificity for the sMCI–cMCI comparison; 92.37% accuracy, 84.78% sensitivity, and 97.22% specificity for the cMCI–NC comparison; and 93.75% accuracy, 92.5% sensitivity, and 94.44% specificity for the sMCI–NC comparison. The best performances obtained by the SVM classifier using the essential features were 5–40% more than those using all of the retained features. The feasibility of the cortical features for the recognition of anatomical patterns was certified; thus, the proposed method has the potential to improve the clinical diagnosis of sub-types of MCI and predict the risk of its conversion to Alzheimer's disease.
- Published
- 2017
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8. Serum per- and polyfluoroalkyl substance (PFAS) levels and health-related biomarkers in a pilot study of skiers in New England.
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Claus Henn B, Leonard ER, Doherty BT, Byrne S, Hartmann N, Ptolemy AS, Ayanian S, and Crawford KA
- Abstract
Background: Per- and polyfluoroalkyl substances (PFAS), synthetic chemicals with adverse health effects, are used extensively in consumer products. Ski waxes, applied to the base of skis, contain up to 100% PFAS by mass, but exposure and health effects are poorly characterized., Objectives: Our objectives were to quantify serum PFAS concentrations among skiers and explore associations with reported ski wax use and biomarkers of cardiometabolic, thyroid, and immune health., Methods: We recruited 30 active adult skiers to provide non-fasting blood samples and complete questionnaires. We quantified 18 PFAS using mass spectrometry, and measured serum lipids, thyroid hormones, and immunoglobulins. We explored associations of individual and aggregate measures of serum PFAS with wax use indicators and health biomarkers using multivariable regression models, adjusted for age and gender identity., Results: Nine PFAS (PFBS, PFHpS, PFHxS, Sm-PFOS, n-PFOS, PFDA, PFNA, PFUnDA, n-PFOA) were detected in 100% of participants, and MeFOSAA in 93%. Compared to NHANES, median serum concentrations (ng/ml) were similar, but higher in coaches (e.g., PFOA
all : 1.1, PFOAcoaches : 2.7, PFOANHANES : 1.2; PFNAall : 0.5, PFNAcoaches : 1.7, PFNANHANES : 0.4). Factors reflecting wax exposure were positively associated with PFAS: e.g., >10 years as a snow sport athlete, compared to <10 years, was associated with 3.2 (95% CI: 0.7, 5.6) ng/ml higher aggregate PFAS, as defined by National Academies of Science, Engineering, and Medicine (NASEM). An IQR (6.3 ng/ml) increase in NASEM PFAS was associated with 32.1 (95% CI: 7.0, 57.2), 35.5 (13.5, 57.5), and 12.8 (0.6, 25.1) mg/dl higher total cholesterol, LDL-C, and sdLDL-C, respectively., Discussion: Our study provides early evidence that recreational skiers, particularly coaches, are exposed to PFAS through ski wax. Several PFAS were associated with higher serum lipids among these physically active adults. Interventions to remove PFAS from fluorinated wax could decrease direct exposure to skiers and reduce PFAS release into the environment., Competing Interests: Declaration of Competing Interest ☒ The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. ☐ The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:, (Copyright © 2024. Published by Elsevier Inc.)- Published
- 2024
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9. Considerations and challenges in support of science and communication of fish consumption advisories for per- and polyfluoroalkyl substances.
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Petali JM, Pulster EL, McCarthy C, Pickard HM, Sunderland EM, Bangma J, Carignan CC, Robuck A, Crawford KA, Romano ME, Lohmann R, and von Stackelburg K
- Abstract
Federal, state, tribal, or local entities in the United States issue fish consumption advisories (FCAs) as guidance for safer consumption of locally caught fish containing contaminants. Fish consumption advisories have been developed for commonly detected compounds such as mercury and polychlorinated biphenyls. The existing national guidance does not specifically address the unique challenges associated with bioaccumulation and consumption risk related to per- and polyfluoroalkyl substances (PFAS). As a result, several states have derived their own PFAS-related consumption guidelines, many of which focus on one frequently detected PFAS, known as perfluorooctane sulfonic acid (PFOS). However, there can be significant variation between tissue concentrations or trigger concentrations (TCs) of PFOS that support the individual state-issued FCAs. This variation in TCs can create challenges for risk assessors and risk communicators in their efforts to protect public health. The objective of this article is to review existing challenges, knowledge gaps, and needs related to issuing PFAS-related FCAs and to provide key considerations for the development of protective fish consumption guidance. The current state of the science and variability in FCA derivation, considerations for sampling and analytical methodologies, risk management, risk communication, and policy challenges are discussed. How to best address PFAS mixtures in the development of FCAs, in risk assessment, and establishment of effect thresholds remains a major challenge, as well as a source of uncertainty and scrutiny. This includes developments better elucidating toxicity factors, exposures to PFAS mixtures, community fish consumption behaviors, and evolving technology and analytical instrumentation, methods, and the associated detection limits. Given the evolving science and public interests informing PFAS-related FCAs, continued review and revision of FCA approaches and best practices are vital. Nonetheless, consistent, widely applicable, PFAS-specific approaches informing methods, critical concentration thresholds, and priority compounds may assist practitioners in PFAS-related FCA development and possibly reduce variability between states and jurisdictions. Integr Environ Assess Manag 2024;00:1-20. © 2024 SETAC., (© 2024 SETAC.)
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- 2024
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10. Plasma per- and polyfluoroalkyl substance mixtures during pregnancy and duration of breastfeeding in the New Hampshire birth cohort study.
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Romano ME, Gallagher LG, Price G, Crawford KA, Criswell R, Baker E, Botelho JC, Calafat AM, and Karagas MR
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- Pregnancy, Female, Humans, Cohort Studies, Breast Feeding, Bayes Theorem, New Hampshire, Alkanesulfonates, Environmental Pollutants, Fluorocarbons, Alkanesulfonic Acids, Caprylates
- Abstract
Background: Prior studies suggest that prenatal per- and polyfluoroalkyl substances (PFAS) exposures are associated with shorter breastfeeding duration. Studies assessing PFAS mixtures and populations in North America are sparse., Methods: We quantified PFAS concentrations in maternal plasma collected during pregnancy in the New Hampshire Birth Cohort Study (2010-2017). Participants completed standardized breastfeeding surveys at regular intervals until weaning (n = 813). We estimated associations between mixtures of 5 PFAS and risk of stopping exclusive breastfeeding before 6 months or any breastfeeding before 12 months using probit Bayesian kernel machine regression. For individual PFAS, we calculated the relative risk and hazard ratio (HR) of stopping breastfeeding using modified Poisson regression and accelerated failure time models respectively., Results: PFAS mixtures were associated with stopping exclusive breastfeeding before 6 months, primarily driven by perfluorooctanoate (PFOA). We observed statistically significant trends in the association of perfluorohexane sulfonate (PFHxS), PFOA, and perfluorononanoate (PFNA) (p-trends≤0.02) with stopping exclusive breastfeeding. Participants in the highest PFOA quartile had a 28% higher risk of stopping exclusive breastfeeding before 6 months compared to those in the lowest quartile (95% Confidence Interval: 1.04, 1.56). Similar trends were observed for PFHxS and PFNA with exclusive breastfeeding (p-trends≤0.05). PFAS were not associated with stopping any breastfeeding before 12 months., Conclusions: In this cohort, we observed that participants with greater overall plasma PFAS concentrations had greater risk of stopping exclusive breastfeeding before 6 months and associations were driven largely by PFOA. These findings further support the growing literature indicating that PFAS may be associated with shorter duration of breastfeeding., (Copyright © 2024 Elsevier GmbH. All rights reserved.)
- Published
- 2024
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11. Respiratory Exposure to Highly Fluorinated Chemicals via Application of Ski Wax and Related Health Effects.
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Crawford KA and Hartmann N
- Subjects
- Humans, Industry, Kidney, Waxes, Carboxylic Acids, Fluorocarbons toxicity
- Abstract
Purpose: Waxes containing per- and polyfluoroalkyl substances (PFAS) are applied to the base of skis and snowboards ("skis") to reduce friction with the snow surface and improve glide. PFAS exposure can adversely impact cardiometabolic, thyroid, liver, kidney, reproductive, and immune health and are associated with increased risk of certain cancers. In the present review, we summarize the state of the science on PFAS exposure from fluorinated ski wax use, including acute respiratory health effects and PFAS concentrations in biological and environmental media collected from ski waxing settings., Recent Findings: Perfluoroalkyl carboxylic acid (PFCA) concentrations in serum and air collected from professional wax technicians and the rooms where waxes are applied are among the highest of any occupation investigated to date, including the fluorochemical industry. High airborne concentrations of fluorotelomer alcohols contribute to high body burdens of certain PFCAs among ski waxers. Fluorinated ski waxes are a significant source of PFAS exposure for people waxing skis and/or spending time in areas where waxing occurs. We highlight recommendations for future research, policy, and technologies needed to address PFAS exposures from fluorinated wax use., (© 2024. The Author(s).)
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- 2024
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12. Non-chemotherapy adjuvant agents in TP53 mutant Ewing sarcoma.
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Kim JA, Crawford KA, Spada PA, Martin LR, Zhang J, Wong R, Reid JM, Stewart CF, Frank TM, Liu Q, Michalek JE, and Keller C
- Subjects
- Humans, Animals, Mice, Enoxacin, Benzamides, Adjuvants, Immunologic, Adjuvants, Pharmaceutic, Disease Models, Animal, Tumor Suppressor Protein p53, Sarcoma, Ewing drug therapy, Neuroectodermal Tumors, Primitive, Peripheral
- Abstract
Ewing sarcoma (EWS) is a malignant tumor arising in bone or soft tissue that occurs in adolescent and young adult patients as well as adults later in life. Although non-metastatic EWS is typically responsive to treatment when newly diagnosed, relapsed cases have an unmet need for which no standard treatment approach exists. Recent phase III clinical trials for EWS comparing 7 vs 5 chemotherapy drugs have failed to improve survival. To extend the durability of remission for EWS, we investigated 3 non-chemotherapy adjuvant therapy drug candidates to be combined with chemotherapy. The efficacy of these adjuvant drugs was investigated via anchorage-dependent growth assays, anchorage-independent soft-agar colony formation assays and EWS xenograft mouse models. Enoxacin and entinostat were the most effective adjuvant drug in both long-term in vitro and in vivo adjuvant studies. In the context that enoxacin is an FDA-approved antibiotic, and that entinostat is an investigational agent not yet FDA-approved, we propose enoxacin as an adjuvant drug for further preclinical and clinical investigation in EWS patients., (© 2023. Springer Nature Limited.)
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- 2023
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13. Predictors of Breastfeeding Duration in the New Hampshire Birth Cohort Study.
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Crawford KA, Gallagher LG, Baker ER, Karagas MR, and Romano ME
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- Infant, Pregnancy, Female, Humans, Child, Adolescent, Young Adult, Adult, Middle Aged, Cohort Studies, New Hampshire, Postpartum Period, Breast Feeding, Cesarean Section
- Abstract
Introduction: Breastfeeding has significant health benefits for infants and birthing persons, including reduced risk of chronic disease. The American Academy of Pediatrics recommends exclusively breastfeeding infants for 6 months and recently extended its recommendation for continuing to breastfeed with supplementation of solid foods from one to two years. Studies consistently identify lower breastfeeding rates among US infants, with regional and demographic variability. We examined breastfeeding in birthing person-infant pairs among healthy, term pregnancies enrolled in the New Hampshire Birth Cohort Study between 2010 and 2017 (n = 1176)., Methods: Birthing persons 18-45 years old were enrolled during prenatal care visits at ~ 24-28 weeks gestation and have been followed since enrollment. Breastfeeding status was obtained from postpartum questionnaires. Birthing person and infant health and sociodemographic information was abstracted from medical records and prenatal and postpartum questionnaires. We evaluated the effects of birthing person age, education, relationship status, pre-pregnancy body mass index, gestational weight gain (GWG), smoking and parity, and infant sex, ponderal index, gestational age and delivery mode on breastfeeding initiation and duration using modified Poisson and multivariable linear regression., Results: Among healthy, term pregnancies, 96% of infants were breastfed at least once. Only 29% and 28% were exclusively breastfed at 6-months or received any breastmilk at 12-months, respectively. Higher birthing person age, education, and parity, being married, excessive GWG, and older gestational age at delivery were associated with better breastfeeding outcomes. Smoking, obesity, and cesarean delivery were negatively associated with breastfeeding outcomes., Conclusions: Given the public health importance of breastfeeding for infants and birthing persons, interventions are needed to support birthing persons to extend their breastfeeding duration., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
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- 2023
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14. Waxing activity as a potential source of exposure to per- and polyfluoroalkyl substances (PFAS) and other environmental contaminants among the US ski and snowboard community.
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Crawford KA, Doherty BT, Gilbert-Diamond D, Romano ME, and Claus Henn B
- Subjects
- Humans, Particulate Matter, Solvents, Waxes toxicity, Fluorocarbons analysis, Skiing
- Abstract
Background: Skiers and snowboarders apply waxes and solvents to their equipment to enhance glide across the snow. Waxing results in exposures to per- and polyfluoroalkyl substances (PFAS) and particulate matter, which have been associated with adverse health effects among professional wax technicians in Scandinavia. However, little is known about exposure among people who participate at other levels of sport, including recreationally, in other regions., Objective: We sought to characterize wax-related exposures among US skiers and snowboarders who participate across numerous levels of sport to expand scientific understanding of environmental health risks among this population., Methods: We used an anonymous electronic survey to evaluate wax-related exposures among US cross-country and downhill skiers and snowboarders. Specifically, we assessed (Fang et al., 2020): duration of time involved with each sport in any role (Freberg et al., 2013), intensity of wax-related exposures based on time spent in waxing areas, wax use, and wax type (Rogowski et al., 2007), frequency of fluorinated wax application, and (Freberg et al., 2010) use of exposure interventions., Results: Participants tended to be long-term winter sports enthusiasts (e.g., median downhill skiing duration: 31 years). Nearly all (92%) participants personally applied some wax to their skis/snowboards and most applied waxes containing PFAS (67%) and solvents (62%). Ski professionals waxed the most pairs of skis with fluorinated waxes annually (median (IQR): 20 (1, 100)), though individuals participating recreationally also applied fluorinated waxes regularly. Exposure interventions were not widely used., Significance: Waxing activities may pose significant risk of exposure to PFAS and other environmental contaminants among the US ski and snowboard community. Efforts are needed to reduce these exposures through changes to wax use patterns and broader adoption of exposure reduction strategies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2022
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15. Functional genomic analysis of epithelioid sarcoma reveals distinct proximal and distal subtype biology.
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Rasmussen SV, Jin JX, Bickford LR, Woods AD, Sahm F, Crawford KA, Nagamori K, Goto H, Torres KE, Sidoni A, Rudzinski ER, Thway K, Jones RL, Ciulli A, Wright H, Lathara M, Srinivasa G, Kannan K, Huang PH, Grünewald TGP, Berlow NE, and Keller C
- Subjects
- Adolescent, Child, Chromosomal Proteins, Non-Histone genetics, Chromosomal Proteins, Non-Histone metabolism, Chromosomal Proteins, Non-Histone therapeutic use, Genomics, Humans, Transcription Factors genetics, Transcription Factors metabolism, Transcription Factors therapeutic use, Young Adult, DNA-Binding Proteins genetics, DNA-Binding Proteins metabolism, DNA-Binding Proteins therapeutic use, Sarcoma drug therapy, Sarcoma genetics, Sarcoma pathology
- Abstract
Background: Metastatic epithelioid sarcoma (EPS) remains a largely unmet clinical need in children, adolescents and young adults despite the advent of EZH2 inhibitor tazemetostat., Methods: In order to realise consistently effective drug therapies, a functional genomics approach was used to identify key signalling pathway vulnerabilities in a spectrum of EPS patient samples. EPS biopsies/surgical resections and cell lines were studied by next-generation DNA exome and RNA deep sequencing, then EPS cell cultures were tested against a panel of chemical probes to discover signalling pathway targets with the most significant contributions to EPS tumour cell maintenance., Results: Other biologically inspired functional interrogations of EPS cultures using gene knockdown or chemical probes demonstrated only limited to modest efficacy in vitro. However, our molecular studies uncovered distinguishing features (including retained dysfunctional SMARCB1 expression and elevated GLI3, FYN and CXCL12 expression) of distal, paediatric/young adult-associated EPS versus proximal, adult-associated EPS., Conclusions: Overall results highlight the complexity of the disease and a limited chemical space for therapeutic advancement. However, subtle differences between the two EPS subtypes highlight the biological disparities between younger and older EPS patients and emphasise the need to approach the two subtypes as molecularly and clinically distinct diseases., (© 2022 The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.)
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- 2022
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16. SMARCA4 biology in alveolar rhabdomyosarcoma.
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Bharathy N, Cleary MM, Kim JA, Nagamori K, Crawford KA, Wang E, Saha D, Settelmeyer TP, Purohit R, Skopelitis D, Chang K, Doran JA, Kirschbaum CW, Bharathy S, Crews DW, Randolph ME, Karnezis AN, Hudson-Price L, Dhawan J, Michalek JE, Ciulli A, Vakoc CR, and Keller C
- Subjects
- Biology, Child, DNA Helicases genetics, Humans, Nuclear Proteins genetics, Transcription Factors genetics, Neoplasms, Rhabdomyosarcoma, Alveolar genetics, Rhabdomyosarcoma, Embryonal
- Abstract
Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children and phenocopies a muscle precursor that fails to undergo terminal differentiation. The alveolar subtype (ARMS) has the poorest prognosis and represents the greatest unmet medical need for RMS. Emerging evidence supports the role of epigenetic dysregulation in RMS. Here we show that SMARCA4/BRG1, an ATP-dependent chromatin remodeling enzyme of the SWI/SNF complex, is prominently expressed in primary tumors from ARMS patients and cell cultures. Our validation studies for a CRISPR screen of 400 epigenetic targets identified SMARCA4 as a unique factor for long-term (but not short-term) tumor cell survival in ARMS. A SMARCA4/SMARCA2 protein degrader (ACBI-1) demonstrated similar long-term tumor cell dependence in vitro and in vivo. These results credential SMARCA4 as a tumor cell dependency factor and a therapeutic target in ARMS., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)
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- 2022
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17. Current Marijuana Use and Alcohol Consumption Among Adults Following the Legalization of Nonmedical Retail Marijuana Sales - Colorado, 2015-2019.
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Crawford KA, Gardner JA, Meyer EA, Hall KE, Gary DS, and Esser MB
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- Adolescent, Adult, Aged, Behavioral Risk Factor Surveillance System, Colorado epidemiology, Female, Humans, Male, Middle Aged, Young Adult, Alcohol Drinking epidemiology, Commerce legislation & jurisprudence, Legislation, Drug, Marijuana Use epidemiology
- Abstract
In Colorado, excessive alcohol use* contributed to $5 billion in economic costs in 2010 (1) and >1,800 deaths annually during 2011-2015 (2). The most common pattern of excessive drinking is binge drinking (consumption of four or more drinks on an occasion for women or five or more drinks for men) (3), which is associated with increased likelihood of using other substances, including marijuana (4). Retail (i.e., nonmedical) marijuana sales began in Colorado on January 1, 2014. The Colorado Department of Public Health and Environment (CDPHE) and CDC used data from Colorado's 2015-2019 Behavioral Risk Factor Surveillance System (BRFSS) to examine current use of marijuana (including hashish) by drinking patterns among 45,991 persons aged ≥18 years who responded to questions about alcohol and marijuana use. The age-standardized, weighted prevalence of current marijuana use among persons who reported binge drinking (34.4%) was significantly higher than the prevalence among current non-binge drinkers (14.8%) and nondrinkers (9.9%). Evidence-based strategies recommended by the Community Preventive Services Task Force to reduce excessive alcohol use and tobacco use (e.g., increasing prices or reducing access) can reduce alcohol- and tobacco-related harms. Similar strategies might be effective in reducing marijuana use and its potential harms as well., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.
- Published
- 2021
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18. The Citizen Psychologist Curriculum-Preparing psychologists for public service: The 2018 American Psychological Association Presidential Initiative.
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Henderson Daniel J, Rozensky RH, Grus CL, Brown KS, Gómez CA, Bruner L, Crawford KA, Hewitt A, McQuaid EL, Mio JS, Montalvan C, Reeb RN, Ruiz A, Sheras P, Siegel W, Taylor JM, Williams W, Ameen EJ, and Andrade J
- Subjects
- Aged, Child, Humans, Curriculum, Societies, Scientific
- Abstract
This article describes a curriculum developed as part of the American Psychological Association President Jessica Henderson Daniel's, 2018 Presidential Initiative-The Citizen Psychologist. The curriculum is designed to prepare the next generation of Citizen Psychologists to provide the broadest sense of service as leaders in their communities and in public service psychology. The curriculum prepares the learner to bring psychological knowledge, science, and expertise to bear on existing challenges to improve community well-being locally, nationally, and globally. This includes addressing the services needs of various vulnerable populations such as veterans, prisoners, the seriously mentally ill, those with substance abuse problems, children, and older adults. Competency-based curricula are presented in a series of modules, each dedicated to a level of education and training from high school through lifelong learning. Each module presents learning outcomes, activities, and resources designed to develop level-specific competencies. Steps for implementation and recommendations at the local and national level are provided. Implications of incorporating the Citizen Psychologist curriculum in education and training programs are discussed including encouraging students to explore volunteer and career opportunities in public service psychology. (PsycInfo Database Record (c) 2021 APA, all rights reserved).
- Published
- 2021
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19. Functional impact of a germline RET mutation in alveolar rhabdomyosarcoma.
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Berlow NE, Crawford KA, Bult CJ, Noakes C, Sloma I, Rudzinski ER, and Keller C
- Subjects
- Animals, Cell Line, Tumor, DNA Mutational Analysis, Genotype, Humans, Mice, Multiple Endocrine Neoplasia Type 2a genetics, Multiple Endocrine Neoplasia Type 2a pathology, Phenotype, Rhabdomyosarcoma, Alveolar drug therapy, Xenograft Model Antitumor Assays, Germ Cells physiology, Germ-Line Mutation, Proto-Oncogene Proteins c-ret genetics, Proto-Oncogene Proteins c-ret metabolism, Rhabdomyosarcoma, Alveolar genetics
- Abstract
Specific mutations in the RET proto-oncogene are associated with multiple endocrine neoplasia type 2A, a hereditary syndrome characterized by tumorigenesis in multiple glandular elements. In rare instances, MEN2A-associated germline RET mutations have also occurred with non-MEN2A associated cancers. One such germline mutant RET mutation occurred concomitantly in a young adult diagnosed with alveolar rhabdomyosarcoma, a pediatric and young adult soft-tissue cancer with a generally poor prognosis. Although tumor tissue samples were initially unable to provide a viable cell culture for study, tumor tissues were sequenced for molecular characteristics. Through a hierarchical clustering approach, the index case sample was matched to several genetically similar cell models, which were transformed to express the same mutant RET as the index case and used to explore potential therapeutic options for mutant RET -bearing alveolar rhabdomyosarcoma. We also determined whether the RET mutation associated with the index case caused synthetic lethality to select clinical agents. From our investigation, we did not identify synthetic lethality associated with the expression of that patient's RET variant, and overall we did not find experimental evidence for the role of RET in rhabdomyosarcoma progression., (© 2021 Berlow et al.; Published by Cold Spring Harbor Laboratory Press.)
- Published
- 2021
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20. Comparison of Recreational Fish Consumption Advisories Across the USA.
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Cleary BM, Romano ME, Chen CY, Heiger-Bernays W, and Crawford KA
- Subjects
- Animals, Fishes, Food Contamination, Humans, Methylmercury Compounds, Polychlorinated Biphenyls
- Abstract
Purpose of Review: Our comparative analysis sought to understand the factors which drive differences in fish consumption advisories across the USA - including exposure scenarios (acute and chronic health risk, non-cancer and cancer health endpoints), toxicity values (reference dose, cancer slope factor, acute tolerance level), and meal size and bodyweight assumptions., Recent Findings: Fish consumption provides essential nutrients but also results in exposure to contaminants such as PCBs and methylmercury. To protect consumers from the risks of fish contaminants, fish consumption advisories are established, most often by state jurisdictions, to estimate the amount of a certain fish species a person could consume throughout their lifetime without harm. However, inconsistencies in advisories across the USA confuse consumers and undermine the public health goals of fish advisory programs. To date, no rigorous comparison of state and national fish consumption advisories has been reported. Our work identifies discrepancies in key assumptions used to derive risk-based advisories between US states, reflecting differences in the interpretation of toxicity science. We also address the implications for these differences by reviewing advisories issued by contiguous states bordering two waterbodies: Lake Michigan and the Lower Mississippi River. Our findings highlight the importance of regional collaboration when issuing advisories, so that consumers of self-caught fish are equipped with clear knowledge to make decisions to protect their health.
- Published
- 2021
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21. The persistence of ancient settlements and urban sustainability.
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Smith ME, Lobo J, Peeples MA, York AM, Stanley BW, Crawford KA, Gauthier N, and Huster AC
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- Agriculture methods, Agriculture trends, Archaeology statistics & numerical data, Cities classification, Cities economics, Emigration and Immigration trends, Environment, Geography, Humans, Models, Theoretical, Population Dynamics trends, Socioeconomic Factors, Urban Population trends, Urban Renewal methods, Urban Renewal statistics & numerical data, Urban Renewal trends, Emigration and Immigration statistics & numerical data, Population Dynamics statistics & numerical data, Sustainable Growth, Urban Population statistics & numerical data, Urbanization
- Abstract
We propose a dedicated research effort on the determinants of settlement persistence in the ancient world, with the potential to significantly advance the scientific understanding of urban sustainability today. Settlements (cities, towns, villages) are locations with two key attributes: They frame human interactions and activities in space, and they are where people dwell or live. Sustainability, in this case, focuses on the capacity of structures and functions of a settlement system (geography, demography, institutions) to provide for continuity of safe habitation. The 7,000-y-old experience of urbanism, as revealed by archaeology and history, includes many instances of settlements and settlement systems enduring, adapting to, or generating environmental, institutional, and technological changes. The field of urban sustainability lacks a firm scientific foundation for understanding the long durée, relying instead on narratives of collapse informed by limited case studies. We argue for the development of a new interdisciplinary research effort to establish scientific understanding of settlement and settlement system persistence. Such an effort would build upon the many fields that study human settlements to develop new theories and databases from the extensive documentation of ancient and premodern urban systems. A scientific foundation will generate novel insights to advance the field of urban sustainability., Competing Interests: The authors declare no competing interest.
- Published
- 2021
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22. Endocrine-disrupting chemicals and breastfeeding duration: a review.
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Criswell R, Crawford KA, Bucinca H, and Romano ME
- Subjects
- Animals, Benzhydryl Compounds toxicity, Breast drug effects, Breast growth & development, Breast physiology, Environmental Exposure adverse effects, Environmental Exposure statistics & numerical data, Female, Humans, Lactation physiology, Mammary Glands, Animal drug effects, Mammary Glands, Animal growth & development, Mammary Glands, Animal physiology, Pesticides toxicity, Phenols toxicity, Phthalic Acids toxicity, Time Factors, Breast Feeding statistics & numerical data, Endocrine Disruptors toxicity, Lactation drug effects
- Abstract
Purpose of Review: The purpose of this review is to describe epidemiologic and toxicological literature investigating how endocrine-disrupting chemicals (EDCs) affect mammary gland development and function, thereby impacting lactation duration., Recent Findings: Perfluoroalkyl and polyfluoroalkyl substances appear to reduce breastfeeding duration through impaired mammary gland development, lactogenesis, and suppressed endocrine signaling. Halogenated aromatic hydrocarbons have differing associations with lactation duration, likely because of the variety of signaling pathways that they affect, pointing to the importance of complex mixtures in epidemiologic studies. Although epidemiologic literature suggests that pesticides and fungicides decrease or have no effect on lactation duration, toxicology literature suggests enhanced mammary gland development through estrogenic and/or antiandrogenic pathways. Toxicological studies suggest that phthalates may affect mammary gland development via estrogenic pathways but no association with lactation duration has been observed. Bisphenol A was associated with decreased duration of breastfeeding, likely through direct and indirect action on estrogenic pathways., Summary: EDCs play a role in mammary gland development, function, and lactogenesis, which can affect breastfeeding duration. Further research should explore direct mechanisms of EDCs on lactation, the significance of toxicant mixtures, and transgenerational effects of EDCs on lactation.
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- 2020
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23. Maternal urinary concentrations of organophosphate ester metabolites: associations with gestational weight gain, early life anthropometry, and infant eating behaviors among mothers-infant pairs in Rhode Island.
- Author
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Crawford KA, Hawley N, Calafat AM, Jayatilaka NK, Froehlich RJ, Has P, Gallagher LG, Savitz DA, Braun JM, Werner EF, and Romano ME
- Subjects
- Adult, Body Composition drug effects, Body Size drug effects, Esters urine, Feeding Behavior drug effects, Female, Humans, Infant, Infant, Newborn growth & development, Pregnancy, Rhode Island, Young Adult, Anthropometry, Environmental Pollutants urine, Gestational Age, Gestational Weight Gain drug effects, Infant, Newborn physiology, Maternal Exposure, Organophosphates urine
- Abstract
Background: Organophosphate esters (OPEs)-used as flame retardants and plasticizers-are associated with adverse pregnancy outcomes such as reduced fecundity and live births and increased preterm delivery. OPEs may interfere with growth and metabolism via endocrine-disruption, but few studies have investigated endocrine-related outcomes. The objective of this pilot study (n = 56 mother-infant pairs) was to evaluate associations of OPEs with gestational weight gain (GWG), gestational age at delivery, infant anthropometry, and infant feeding behaviors., Methods: We quantified OPE metabolites (bis-2-chloroethyl phosphate [BCEP], bis (1,3-dichloro-2-propyl) phosphate [BDCPP], diphenyl phosphate [DPHP]) in pooled maternal spot urine collected throughout pregnancy (~ 12, 28, and 35 weeks' gestation). We obtained maternal sociodemographic characteristics from questionnaires administered at enrollment and perinatal characteristics from medical record abstraction. Trained research assistants measured infant weight, length, head and abdominal circumferences, and skinfold thicknesses at birth and 6 weeks postpartum. Mothers reported infant feeding behavior via the Baby Eating Behavior Questionnaire (BEBQ). Using multiple linear regression, we assessed associations of log
2 -transformed maternal urinary OPE metabolites with GWG, gestational age at delivery, infant anthropometry at birth, weekly growth rate, and BEBQ scores at 6 weeks postpartum. We used linear mixed effects (LME) models to analyze overall infant anthropometry during the first 6 weeks of life. Additionally, we considered effect modification by infant sex., Results: We observed weak positive associations between all OPE metabolites and GWG. In LME models, BDCPP was associated with increased infant length (β = 0.44 cm, 95%CI = 0.01, 0.87) and weight in males (β = 0.14 kg, 95%CI = 0.03, 0.24). BDCPP was also associated with increased food responsiveness (β = 0.23, 95%CI = 0.06, 0.40). DPHP was inversely associated with infant abdominal circumference (β = - 0.50 cm, 95%CI = - 0.86, - 0.14) and female weight (β = - 0.19 kg, 95%CI = - 0.36, - 0.02), but positively associated with weekly growth in iliac skinfold thickness (β = 0.10 mm/wk., 95%CI = 0.02, 0.19). Further, DPHP was weakly associated with increased feeding speed. BCEP was associated with greater infant thigh skinfold thickness (β = 0.34 mm, 95%CI = 0.16, 0.52) and subscapular skinfold thickness in males (β = 0.14 mm, 95%CI = 0.002, 0.28)., Conclusions: Collectively, these findings suggest that select OPEs may affect infant anthropometry and feeding behavior, with the most compelling evidence for BDCPP and DPHP.- Published
- 2020
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24. Case report for an adolescent with germline RET mutation and alveolar rhabdomyosarcoma.
- Author
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Crawford KA, Berlow NE, Tsay J, Lazich M, Mancini M, Noakes C, Huang T, and Keller C
- Subjects
- Adolescent, Alleles, Amino Acid Substitution, Biopsy, DNA Mutational Analysis, Genotype, Humans, Immunohistochemistry, Male, Phenotype, Positron-Emission Tomography, Protein Kinase Inhibitors pharmacology, Proto-Oncogene Proteins c-ret metabolism, Radiography, Thoracic, Rhabdomyosarcoma, Alveolar drug therapy, Rhabdomyosarcoma, Alveolar metabolism, Genetic Association Studies, Genetic Predisposition to Disease, Germ-Line Mutation, Proto-Oncogene Proteins c-ret genetics, Rhabdomyosarcoma, Alveolar diagnosis, Rhabdomyosarcoma, Alveolar genetics
- Abstract
In this case report we evaluate the genetics of and scientific basis of therapeutic options for a 14-yr-old male patient diagnosed with metastatic PAX3-FOXO1 fusion positive alveolar rhabdomyosarcoma. A distinguishing genetic feature of this patient was a germline RET C634F mutation, which is a known driver of multiple endocrine neoplasia type 2A (MEN2A) cancer. Through sequential DNA and RNA sequencing analyses over the patient's clinical course, a set of gene mutations, amplifications, and overexpressed genes were identified and biological hypotheses generated to explore the biology of RET and coexisting signaling pathways in rhabdomyosarcoma. Somatic genetic abnormalities identified include CDK4 amplification and FGFR4 G388R polymorphism. Because of the initial lack of patient-derived primary cell cultures, these hypotheses were evaluated using several approaches including western blot analysis and pharmacological evaluation with molecularly similar alveolar rhabdomyosarcoma cell lines. Once a primary cell culture became available, the RET inhibitor cabozantinib was tested but showed no appreciable efficacy in vitro, affirming with the western blot negative for RET protein expression that RET germline mutation could be only incidental. In parallel, the patient was treated with cabozantinib without definitive clinical benefit. Parallel chemical screens identified PI3K and HSP90 as potential tumor-specific biological features. Inhibitors of PI3K and HSP90 were further validated in drug combination synergy experiments and shown to be synergistic in the patient-derived culture. We also evaluated the use of JAK/STAT pathway inhibitors in the context of rhabdomyosarcomas bearing the FGFR4 G388R coding variant. Although the patient succumbed to his disease, study of the patient's tumor has generated insights into the biology of RET and other targets in rhabdomyosarcoma., (© 2020 Crawford et al.; Published by Cold Spring Harbor Laboratory Press.)
- Published
- 2020
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25. Undifferentiated small round cell sarcoma in a young male: a case report.
- Author
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Ricker CA, Berlow NE, Crawford KA, Georgopapadakos T, Huelskamp AN, Woods AD, Dhimolea E, Ramkissoon SH, Spunt SL, Rudzinski ER, and Keller C
- Subjects
- Alleles, Biomarkers, Tumor, Biopsy, Child, Chromosome Mapping, Computational Biology, Gene Expression, Genomics, HLA Antigens genetics, Humans, Immunohistochemistry, Magnetic Resonance Imaging, Male, Neoplasm Grading, Oncogene Proteins, Fusion genetics, Sarcoma, Small Cell etiology, Symptom Assessment, Translocation, Genetic, Whole Genome Sequencing, Sarcoma, Small Cell diagnosis
- Abstract
CIC -rearranged sarcomas (CRSs) have recently been characterized as a distinct sarcoma subgroup with a less favorable prognosis compared to other small round cell sarcomas. CRSs share morphologic features with Ewing's sarcoma and prior to 2013 were grouped under undifferentiated sarcomas with round cell phenotype by the WHO classification. In this report, whole-genome sequencing and RNA sequencing were performed for an adolescent male patient with CRS who was diagnosed with undifferentiated pleomorphic sarcoma (UPS) by three contemporary institutions. Somatic mutation analysis identified mutations in IQGAP1 , CCNC , and ATXN1L in pre- and post-treatment tissue samples, as well as a CIC-DUX4 fusion that was confirmed by qPCR and DUX4 immunohistochemistry. Of particular interest was the overexpression of the translation factor eEF1A1 , which has oncogenic properties and has recently been identified as a target of the investigational agent plitidepsin. This case may provide a valuable waypoint in the understanding and classification of CRSs and may provide a rationale for targeting eEF1A1 in similar soft tissue sarcoma cases., (© 2020 Ricker et al.; Published by Cold Spring Harbor Laboratory Press.)
- Published
- 2020
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26. Tributyltin disrupts fin development in Fundulus heteroclitus from both PCB-sensitive and resistant populations: Investigations of potential interactions between AHR and PPARγ.
- Author
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Crawford KA, Clark BW, Heiger-Bernays WJ, Karchner SI, Hahn ME, Nacci DE, and Schlezinger JJ
- Subjects
- Animal Fins abnormalities, Animals, Drug Resistance drug effects, Drug Synergism, Embryo, Nonmammalian abnormalities, Embryo, Nonmammalian metabolism, Embryonic Development drug effects, Gene Expression Regulation, Developmental drug effects, Massachusetts, PPAR gamma genetics, Receptor Cross-Talk, Receptors, Aryl Hydrocarbon genetics, Signal Transduction drug effects, Animal Fins drug effects, Embryo, Nonmammalian drug effects, Fundulidae, PPAR gamma metabolism, Polychlorinated Biphenyls toxicity, Receptors, Aryl Hydrocarbon metabolism, Trialkyltin Compounds toxicity, Water Pollutants, Chemical toxicity
- Abstract
Tributyltin (TBT) and dioxin-like polychlorinated biphenyls (PCBs) are environmental contaminants that are highly toxic to fish and co-occur in New Bedford Harbor (NBH), an estuarine Superfund site located in Massachusetts, USA. Atlantic killifish (Fundulus heteroclitus) that reside in NBH (and other highly contaminated sites along the east coast of the United States) have developed resistance to activation of the aryl hydrocarbon receptor (AHR) pathway and the toxicity of dioxin-like chemicals, such as 3,3',4,4',5-pentachlorobiphenyl, PCB126. In many biological systems, TBT disregulates adipose and bone development via the PPARγ-RXR pathway; AHR activation also disrupts adipose and bone homeostasis, potentially through molecular crosstalk between AHR and PPARγ. However, little is known about how co-exposure and the interaction of these pathways modulate the toxicological effects of these contaminants. Here, we tested the hypotheses that TBT would induce teratogenesis in killifish via activation of PPARγ and that PCB126 co-exposure would suppress PPARγ pathway activation in PCB-sensitive killifish from a reference site (Scorton Creek, SC, PCB-sensitive) but not in PCB-tolerant NBH killifish. Killifish embryos from both populations exposed to TBT (50 and 100 nM) displayed caudal fin deformities. TBT did not change the expression of pparg or its target genes related to adipogenesis (fabp11a and fabp1b) in either population. However, expression of osx/sp7, an osteoblast marker gene, and col2a1b, a chondroblast marker gene, was significantly suppressed by TBT only in SC killifish. An RXR-specific agonist, but not a PPARγ-specific agonist, induced caudal fin deformities like those observed in TBT-treated embryos. PCB126 did not induce caudal fin deformities and did not exacerbate TBT-induced fin deformities. Further, PCB126 increased expression of pparg in SC embryos and not NBH embryos, but did not change the expression of fabp1b. Taken together, these results suggest that in killifish embryos the PPARγ pathway is regulated in part by AHR, but is minimally active at least in this early life stage. In killifish, RXR activation, rather than PPARγ activation, appears to be the mechanism by which TBT induces caudal fin teratogenicity, which is not modulated by AHR responsiveness., (Copyright © 2019 Elsevier B.V. All rights reserved.)
- Published
- 2020
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27. Altered lipid homeostasis in a PCB-resistant Atlantic killifish (Fundulus heteroclitus) population from New Bedford Harbor, MA, U.S.A.
- Author
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Crawford KA, Clark BW, Heiger-Bernays WJ, Karchner SI, Claus Henn BG, Griffith KN, Howes BL, Schlezinger DR, Hahn ME, Nacci DE, and Schlezinger JJ
- Subjects
- Animals, Environmental Exposure adverse effects, Gene Expression Regulation drug effects, Homeostasis drug effects, Homeostasis genetics, Lipid Metabolism genetics, Liver drug effects, Liver metabolism, Male, Massachusetts, Receptors, Aryl Hydrocarbon genetics, Adaptation, Physiological drug effects, Fundulidae metabolism, Lipid Metabolism drug effects, Polychlorinated Biphenyls toxicity, Receptors, Aryl Hydrocarbon metabolism, Water Pollutants, Chemical toxicity
- Abstract
Sentinel species such as the Atlantic killifish (Fundulus heteroclitus) living in urban waterways can be used as toxicological models to understand impacts of environmental metabolism disrupting compound (MDC) exposure on both wildlife and humans. Exposure to MDCs is associated with increased risk of metabolic syndrome, including impaired lipid and glucose homeostasis, adipogenesis, appetite control, and basal metabolism. MDCs are ubiquitous in the environment, including in aquatic environments. New Bedford Harbor (NBH), Massachusetts is polluted with polychlorinated biphenyls (PCBs), and, as we show for the first time, tin (Sn). PCBs and organotins are ligands for two receptor systems known to regulate lipid homeostasis, the aryl hydrocarbon receptor (AHR) and the peroxisome proliferator-activated receptors (PPARs), respectively. In the current study, we compared lipid homeostasis in laboratory-reared killifish from NBH (F2) and a reference location (Scorton Creek, Massachusetts; F1 and F2) to evaluate how adaptation to local conditions may influence responses to MDCs. Adult killifish from each population were exposed to 3,3',4,4',5-pentachlorobiphenyl (PCB126, dioxin-like), 2,2',4,4',5,5'-hexachlorobiphenyl (PCB153, non-dioxin-like), or tributyltin (TBT, a PPARγ ligand) by a single intraperitoneal injection and analyzed after 3 days. AHR activation was assessed by measuring cyp1a mRNA expression. Lipid homeostasis was evaluated phenotypically by measuring liver triglycerides and organosomatic indices, and at the molecular level by measuring the mRNA expression of pparg and ppara and a target gene for each receptor. Acute MDC exposure did not affect phenotypic outcomes. However, overall NBH killifish had higher liver triglycerides and adiposomatic indices than SC killifish. Both season and population were significant predictors of the lipid phenotype. Acute MDC exposure altered hepatic gene expression only in male killifish from SC. PCB126 exposure induced cyp1a and pparg, whereas PCB153 exposure induced ppara. TBT exposure did not induce ppar-dependent pathways. Comparison of lipid homeostasis in two killifish populations extends our understanding of how MDCs act on fish and provides a basis to infer adaptive benefits of these differences in the wild., (Copyright © 2019 Elsevier B.V. All rights reserved.)
- Published
- 2019
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28. Faculty Development- Is Some Better Than None?
- Author
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Crawford KA, Wood TJ, Lalonde KA, and Dudek N
- Abstract
This article was migrated. The article was marked as recommended. Introduction: With the advent of competency-based medical education there is an emphasis on formative workplace based assessment. The quality of these assessments is a concern for medical educators and their trainees. Faculty development (FD) strategies to improve assessment quality have resulted in some success. However, few faculty participate, and those who do are likely more motivated to improve, making it difficult to demonstrate a conclusive benefit. To address these weaknesses, we designed a FD initiative to improve the quality of completed in-training evaluation reports (ITERs). All faculty within a division participated. We hypothesized that clinical supervisors would improve their ITER quality based on feedback, regardless of their own motivation to do so, with a simple, point-in-time intervention. Methods: In this three-phase study, two independent raters used the Completed Clinical Evaluation Report Rating (CCERR) to assess the quality of ITERs completed by all faculty in the Division of Orthopedic Surgery at the University of Ottawa. In phase one, ITERs from the previous nine months were evaluated. In phase two, the participants were aware that their ITERs were being evaluated, but they did not receive feedback. In phase three, participants received regular feedback on their performance in the form of their mean CCERR scores. Mean CCERR scores from the different phases of the study were compared. Results: CCERR scores were similar for all three phases (one: 17.56 ± 1.02, two: 17.65 ± 0.96, three: 17.54 ± 0.75, p=0.98). Discussion and Conclusions: There was no evidence in our study that participants' improved their ITER quality despite being aware that they were being evaluated and/or receiving feedback. Potentially, this was related to a lack of motivation. Alternatively, the intensity and/or frequency of the feedback may have been inadequate to create change. These results raise concerns that some faculty development may not necessarily be better than none., (Copyright: © 2019 Crawford KA et al.)
- Published
- 2019
- Full Text
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29. US of Right Upper Quadrant Pain in the Emergency Department: Diagnosing beyond Gallbladder and Biliary Disease.
- Author
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Joshi G, Crawford KA, Hanna TN, Herr KD, Dahiya N, and Menias CO
- Subjects
- Contrast Media, Diagnosis, Differential, Digestive System Diseases diagnostic imaging, Humans, Thoracic Diseases diagnostic imaging, Urologic Diseases diagnostic imaging, Vascular Diseases diagnostic imaging, Abdominal Pain diagnostic imaging, Abdominal Pain etiology, Emergency Service, Hospital, Ultrasonography methods
- Abstract
Acute cholecystitis is the most common diagnosable cause for right upper quadrant abdominal (RUQ) pain in patients who present to the emergency department (ED). However, over one-third of patients initially thought to have acute cholecystitis actually have RUQ pain attributable to other causes. Ultrasonography (US) is the primary imaging modality of choice for initial imaging assessment and serves as a fast, cost-effective, and dynamic modality to provide a definitive diagnosis or a considerably narrowed list of differential possibilities. Multiple organ systems are included at standard RUQ US, and a variety of ultrasonographically diagnosable disease processes can be identified, including conditions of hepatic, pancreatic, adrenal, renal, gastrointestinal, vascular, and thoracic origin, all of which may result in RUQ pain. In certain cases, subsequent computed tomography, magnetic resonance (MR) imaging, MR cholangiopancreatography, or cholescintigraphy may be considered, depending on the clinical situation and US findings. Familiarity with the spectrum of disease processes outside of the gallbladder and biliary tree that may manifest with RUQ pain and recognition at US of these alternative conditions is pivotal for early diagnosis and appropriate management. Diagnosis at the time of initial US can reduce unnecessary imaging and its consequences, including excess cost, radiation exposure, nephrotoxic contrast medium use, and time to diagnosis, thereby translating into improved patient care and outcome. This article (a) reviews the causes of RUQ pain identifiable at US using an organ-system approach, (b) illustrates the US appearance of select conditions from each organ system with multimodality imaging correlates, and (c) discusses the relevant pathophysiology and treatment of these entities to aid in efficient direction of management. Online supplemental material is available for this article.
© RSNA, 2018.- Published
- 2018
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30. Providing 360-degree multisource feedback to nurse educators in the country of Georgia: a formative evaluation of acceptability.
- Author
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DeStephano CC, Crawford KA, Jashi M, and Wold JL
- Subjects
- Georgia (Republic), Humans, Models, Educational, Nursing Evaluation Research, Pilot Projects, Education, Nursing, Baccalaureate organization & administration, Education, Nursing, Baccalaureate standards, Faculty, Nursing standards, Feedback, International Educational Exchange
- Abstract
Background: Due to insufficient nursing education standards in the country of Georgia, 15 health professionals participated in a USAID grant-funded nurse educator faculty development program. These educators then offered continuing education courses and taught more than 1,700 practicing Georgian nurses over 3 years., Method: Using a 360-degree multisource feedback model (MSF), self, video, learner, peer, and program coordinator evaluations of teaching effectiveness were completed. After nurse educators reviewed their results and identified areas for improvement, a questionnaire about the perceived acceptability of teacher evaluations was completed., Results: Of the 15 nurse educators, 93.3% indicated that nurse educators should receive feedback through self, learner, peer, and video evaluations, and 100% indicated that nurse educators should receive feedback from the program coordinator. The accuracy and usefulness of the program coordinator evaluation was rated the highest, whereas peer evaluation was rated the lowest., Conclusion: This study revealed that MSF was acceptable to Georgian nurse educators., (Copyright 2014, SLACK Incorporated.)
- Published
- 2014
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31. Development of clinical practice guidelines.
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Hollon SD, Areán PA, Craske MG, Crawford KA, Kivlahan DR, Magnavita JJ, Ollendick TH, Sexton TL, Spring B, Bufka LF, Galper DI, and Kurtzman H
- Subjects
- Evidence-Based Practice methods, Humans, National Academies of Science, Engineering, and Medicine, U.S., Health and Medicine Division, Societies, Scientific, United States, Evidence-Based Medicine methods, Practice Guidelines as Topic standards, Psychiatry standards, Psychology standards
- Abstract
Clinical practice guidelines (CPGs) are intended to improve mental, behavioral, and physical health by promoting clinical practices that are based on the best available evidence. The American Psychological Association (APA) is committed to generating patient-focused CPGs that are scientifically sound, clinically useful, and informative for psychologists, other health professionals, training programs, policy makers, and the public. The Institute of Medicine (IOM) 2011 standards for generating CPGs represent current best practices in the field. These standards involve multidisciplinary guideline development panels charged with generating recommendations based on comprehensive systematic reviews of the evidence. The IOM standards will guide the APA as it generates CPGs that can be used to inform the general public and the practice community regarding the benefits and harms of various treatment options. CPG recommendations are advisory rather than compulsory. When used appropriately, high-quality guidelines can facilitate shared decision making and identify gaps in knowledge.
- Published
- 2014
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32. A wheelchair workshop for medical students improves knowledge and skills: a randomized controlled trial.
- Author
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Kirby RL, Crawford KA, Smith C, Thompson KJ, and Sargeant JM
- Subjects
- Adult, Curriculum, Female, Humans, Male, Attitude of Health Personnel, Clinical Competence, Education, Medical, Students, Medical, Wheelchairs
- Abstract
Objective: To test the hypothesis that a multicomponent workshop about wheelchairs, tailored for undergraduate medical students, is effective in improving medical students' wheelchair-related knowledge, skills, and attitudes., Design: A randomized controlled trial of 24 first- and second-year medical students randomly allocated into intervention and control groups was undertaken. The intervention group received a 4-hr workshop that included didactic, practical, community, and reflective elements. The educational objectives were validated by a focus group. The main outcome measures were a written knowledge test, a practical examination, the Scale of Attitudes Toward Disabled Persons, and students' perceptions., Results: The baseline characteristics of the groups were comparable. After the workshop, the mean scores on the written knowledge test and practical examination for the intervention group were higher than for the control group by 23.9% (95% confidence interval, 17.6%-30.3%; P < 0.0001) and 34.4% (95% confidence interval, 26.3%-42.5%; P < 0.0001), respectively. The difference (-1.6%) for the Scale of Attitudes Toward Disabled Persons scores was not significant (P = 0.93), but there may have been a ceiling effect (both groups' mean scores were >87%). The perceptions of the students who took the workshop were highly positive., Conclusions: A wheelchair workshop designed for medical students was practical, well received by students, and effective at improving students' knowledge and skills. Although students' attitudes were not measurably affected by the intervention, there was qualitative evidence of a positive effect.
- Published
- 2011
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33. Critical incident stress management and the Office of the Chief Medical Examiner: preliminary inquiry.
- Author
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Crawford KA and Flannery RB Jr
- Subjects
- Bereavement, Boston, Cultural Diversity, Death, Sudden, Humans, Survivors psychology, Coroners and Medical Examiners, Crisis Intervention
- Abstract
In critical incidents that involve loss of life, the Office of the Chief Medical Examiner (ME) is an integral part of the response team. It is the ME who determines the cause of death, explains the circumstances to family survivors, and releases the remains in a timely fashion. In the conduct of the ME's work, addressing the psychological needs of acutely grieving family survivors is important (Kaplan & Sadock, 1998). The importance of this support is becoming increasingly apparent both in supporting surviving family members and for ME staff in assisting families of deceased persons (Coburn, Borges, Knake, & Harper, 2000). Additionally, the work of the medical examiner is often highly stressful to the ME staff as well (Murphy, 2000). The ME staff is continuously exposed to stressful incidents and must interact with traumatized family members. This paper outlines a unique Critical Incident Stress Management (CISM) programmatic effort between Boston University School of Medicine's Center for Multicultural Mental Health and the office of the ME in Massachusetts to enhance the skills cf ME staff in working with family survivors of victims of sudden deaths (i.e., sudden accidents or suspicious deaths) and to address the emotional needs of ME staff themselves. Preliminary anecdotal findings and directions for future experimental inquiry are presented.
- Published
- 2002
34. Identification and cloning of a locus of serine repeat antigen (sera)-related genes from Plasmodium vivax.
- Author
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Kiefer MC, Crawford KA, Boley LJ, Landsberg KE, Gibson HL, Kaslow DC, and Barr PJ
- Subjects
- Amino Acid Sequence, Animals, Base Sequence, Cloning, Molecular, DNA Primers genetics, DNA, Complementary genetics, DNA, Protozoan genetics, Molecular Sequence Data, Multigene Family, Plasmodium vivax growth & development, Polymerase Chain Reaction, Repetitive Sequences, Nucleic Acid, Restriction Mapping, Sequence Homology, Amino Acid, Antigens, Protozoan genetics, Genes, Protozoan, Plasmodium vivax genetics, Plasmodium vivax immunology
- Abstract
Polymerase chain reaction (PCR) primers based on the cysteine proteinase-like active site regions of the Plasmodium falciparum serine repeat antigen (SERA) were used to identify related sequences within the genome of P. vivax. Molecular cloning and sequence analysis of approximately 25 kb of P. vivax genomic DNA revealed a cluster of five repeated SERA-like genes (V-SERA-1-5), each encoding a cysteine proteinase-related protein. In addition to DNA sequence homology, significant similarities in deduced intron/exon organizations were also observed. The characteristic polyserine sequence found in SERA was not present in any of the deduced V-SERA sequences. Instead, in this region of the five genes, considerable sequence differences were found, suggesting the potential for antigenic variation in the V-SERA molecules. In common with SERA, however, the codon at the position corresponding to the active site cysteine residue of active mammalian and plant cysteinyl proteinases was found to be that of a serine residue in each of the V-SERA genes. Furthermore, in four of the five genes, including the expressed V-SERA-5 gene, the codon for the active site histidine residue was changed to that of a leucine residue. These critical differences reinforce the concept that a biological activity other than proteolysis is likely to be the primary function of the proteins encoded by this family of genes.
- Published
- 1996
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35. Correlation of age-associated increases in follicle stimulating hormone secretion with decreases in antral follicles: failure of progesterone-induced acyclicity to prevent these changes.
- Author
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Crawford KA, Hirshfield AN, and De Paolo LV
- Subjects
- Aging pathology, Animals, Estrus drug effects, Estrus physiology, Female, Organ Size drug effects, Ovarian Follicle drug effects, Progesterone pharmacology, Rats, Rats, Inbred Strains, Thymus Gland drug effects, Thymus Gland pathology, Aging physiology, Follicle Stimulating Hormone metabolism, Ovarian Follicle physiology
- Abstract
It is well known that the number of follicles in the mammalian ovary decreases with age. In light of previous data from this laboratory showing age-related alterations in the secretion and production of follicle-stimulating hormone (FSH) in rats by 5-6 months of age, one objective of the present study was to determine if alterations in FSH secretion were accompanied by changes in the number of antral follicles. A second objective of this study was to determine whether or not interruption of cyclic activity by continuous progesterone (P) treatment could decelerate age-associated changes in FSH secretion possibly by retarding the depletion of follicles through ovulation. For this study, one group of 4-day cycling, 7-week-old rats received one empty Silastic implant while another group received 3-40 mm implants containing 30 mm crystalline P. Implants were replaced every 2 weeks until the animals were 5 months old. Progesterone-implanted rats were acyclic during treatment exhibiting predominantly leukocytic vaginal smears. Regular 4-day cycles resumed when P implants were withdrawn (rats approximately 5-6-months-old). A group of 2-3-month-old untreated rats were used for comparison. As expected from our previous results, serum FSH levels at 1600 h on estrus were significantly higher in 5-6-month-old rats receiving empty capsules than in younger rats. Serum FSH concentrations measured in P-treated rats at this time also were significantly higher than levels of this gonadotropin measured in younger rats. Ovaries of older control and P-treated rats contained significantly fewer medium and large antral follicles (greater than 250 microns) than the ovaries of younger rats despite the curtailment of estrous cyclicity and ovulation by continuous P treatment. Interestingly, P treatment prevented the age-associated decrease in thymus weight. Taken together, the present observations suggest that a decrease in the number of growing follicles may be a factor contributing to early age-related alterations in FSH secretion. Furthermore, the prevention (at least temporarily) of age-related thymic involution by P treatment may be indicative of an interrelationship between thymic and reproductive aging.
- Published
- 1992
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36. Evidence for immune selection of hepatitis C virus (HCV) putative envelope glycoprotein variants: potential role in chronic HCV infections.
- Author
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Weiner AJ, Geysen HM, Christopherson C, Hall JE, Mason TJ, Saracco G, Bonino F, Crawford K, Marion CD, and Crawford KA
- Subjects
- Amino Acid Sequence, Cloning, Molecular, DNA, Viral genetics, Enzyme-Linked Immunosorbent Assay, Hepacivirus genetics, Hepacivirus isolation & purification, Hepatitis C microbiology, Humans, Molecular Sequence Data, Peptides chemical synthesis, Peptides immunology, Polymerase Chain Reaction methods, Probability, Protein Conformation, RNA, Viral genetics, RNA, Viral isolation & purification, Viral Envelope Proteins genetics, Genetic Variation, Hepacivirus immunology, Hepatitis C immunology, Viral Envelope Proteins immunology
- Abstract
E2/nonstructural protein 1, the putative envelope glycoprotein (gp72) of HCV, possesses an N-terminal hypervariable (E2 HV) domain from amino acids 384 to 414 of unknown significance. The high degree of amino acid sequence variation in the E2 HV domain appears to be comparable to that observed in the human immunodeficiency virus type 1 gp120 V3 domain. This observation and the observation that the HCV E2 HV domain lacks conserved secondary structure imply that, like the V3 loop of human immunodeficiency virus 1 gp120, the N-terminal E2 region may encode protective epitopes that are subject to immune selection. Antibody-epitope binding studies revealed five isolate-specific linear epitopes located in the E2 HV region. These results suggest that the E2 HV domain is a target for the human immune response and that, in addition to the three major groups of HCV, defined by nucleotide and amino acid sequence identity among HCV isolates, E2 HV-specific subgroups also exist. Analysis of the partial or complete E2 sequences of two individuals indicated that E2 HV variants can either coexist simultaneously in a single individual or that a particular variant may predominate during different episodes of disease. In the latter situation, we found one individual who developed antibodies to a subregion of the E2 HV domain (amino acids 396-407) specific to a variant that was predominant during one major episode of hepatitis but who lacked detectable antibodies to the corresponding region of a second variant that was predominant during a later episode of disease. The data suggest that the variability in the E2 HV domain may result from immune selection. The findings of this report could impact vaccine strategies and drug therapy programs designed to control and eliminate HCV.
- Published
- 1992
- Full Text
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37. Sequence variation in hepatitis C viral isolates.
- Author
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Weiner AJ, Christopherson C, Hall JE, Bonino F, Saracco G, Brunetto MR, Crawford K, Marion CD, Crawford KA, and Venkatakrishna S
- Subjects
- Amino Acid Sequence, Capsid genetics, Hepacivirus isolation & purification, Humans, Molecular Sequence Data, Viral Core Proteins genetics, Genome, Viral, Hepacivirus genetics, Viral Proteins genetics
- Published
- 1991
- Full Text
- View/download PDF
38. Improving the visual discrimination of mentally retarded children: a training strategy.
- Author
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Crawford KA and Siegel PS
- Subjects
- Adolescent, Child, Cues, Feedback, Humans, Psychological Theory, Transfer, Psychology, Attention, Discrimination Learning, Intellectual Disability psychology, Visual Perception
- Abstract
Mentally retarded children were asked to judge whether a series of visual stimuli matched a standard. With each judgment the investigator verbalized "right" or "wrong" and then provided full feedback of particulars, indicating with gesture and words the cue similarities and differences that supported each correct and each incorrect judgment. Control subjects were either given no training (test--retest only) or were asked to make the judgments but given no feedback. Attesting to the efficacy of the training procedure, the trained subjects exhibited total intradimensional transfer; the control subjects, none. The results were related to the attention-retention theory of discrimination learning developed by Fisher and Zeaman and to the "differentiation" methodology and theory presented by Gibson and Gibson.
- Published
- 1982
39. Dopamine metabolism and receptor sensitivity in rat brain after REM sleep deprivation.
- Author
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Farber J, Miller JD, Crawford KA, and McMillen BA
- Subjects
- Animals, Cerebral Cortex metabolism, Corpus Striatum metabolism, Male, Rats, Rats, Inbred Strains, Spiperone metabolism, Synaptic Membranes metabolism, Tyrosine 3-Monooxygenase metabolism, Brain metabolism, Dopamine metabolism, Receptors, Dopamine metabolism, Sleep Deprivation physiology, Sleep, REM physiology
- Abstract
Different dopaminergic mechanisms that could explain behavioral supersensitivity to amphetamine or apomorphine in REM-deprived rats were examined. Four days of REM sleep deprivation induced a highly significant elevation in striatal DOPAC relative to normal controls, but not to stress controls. DOPAC levels in frontal cortex were not affected in any of the groups. Post synaptic D2 receptor number (Bmax) and affinity (Kd) were unchanged in both terminal regions. Similarly, no changes in pre-synaptic receptor sensitivity (apomorphine-induced inhibition of tyrosine hydroxylase) occurred in striatum. A stress control group exhibited no changes in any of the biochemical measures in comparison with either the REM deprived group or unstressed controls. Thus, the enhanced response to dopamine agonists reported previously is not due to altered dopamine receptor sensitivity. Alternative hypotheses to explain enhanced responses to direct and indirect acting dopamine agonists are discussed.
- Published
- 1983
- Full Text
- View/download PDF
40. Attention in discrimination learning in relation to certain teacher-rated behavior anomalies.
- Author
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Siegel PS, Crawford KA, and Evelsizer Z
- Subjects
- Adolescent, Child, Child Behavior, Humans, Hyperkinesis, Psychomotor Performance, Teaching, Attention, Discrimination Learning, Intellectual Disability psychology
- Abstract
Teacher ratings of the anomalous classroom behaviors hyperactivity, inattention, perceptual-motor impairment, perserveration, and stereotypy were examined as predictors of performance on a visual discrimination task. Weak but statistically reliable correlations were obtained.
- Published
- 1985
41. Efficacy of amoscanate against experimental schistosomal infections in monkeys.
- Author
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Crawford KA, Asch HL, Bruce JI, Bueding E, and Smith ER
- Subjects
- Animals, Cebus, Diphenylamine analogs & derivatives, Diphenylamine toxicity, Drug Evaluation, Preclinical, Drug Therapy, Combination, Erythromycin therapeutic use, Female, Macaca mulatta, Male, Parasite Egg Count, Schistosoma haematobium, Schistosoma japonicum, Schistosoma mansoni, Schistosomiasis pathology, Thiocyanates toxicity, Aniline Compounds therapeutic use, Diphenylamine therapeutic use, Isothiocyanates, Schistosomiasis drug therapy, Schistosomicides therapeutic use, Thiocyanates therapeutic use
- Abstract
The antischistosomal activity of oral doses of amoscanate (4-isothiocyanato-4'-nitrodiphenylamine) was determined in infected Cebus apella (capuchin monkeys) and Macaca mulatta (rhesus monkeys). In C. apella infected with Schistosoma japonicum or S. mansoni an initial dose of 10 mg/kg body weight did not alter fecal egg counts, but a subsequent dose of 25 mg/kg markedly reduced both egg counts and worm burdens; in animals infected with S. haematobium, a single dose of 25 mg/kg of amoscanate was similarly effective. Comparable schistosomicidal effects were also produced in S. japonicum- and S. mansoni-infected M. mulatta by single oral doses of 20 and 35 mg/kg, respectively. In both C. apella and M. mulatta the coadministration of single oral doses of 50 or 75 mg/kg of erythromycin attenuated the appearance of mutagenic metabolites of amoscanate in the urine but did not interfere with the antischistosomal action of amoscanate. In non-infected monkeys single oral doses of 75 mg/kg of amoscanate with or without erythromycin (50 mg/kg in C. apella or 75 mg/kg in M. mulatta) did not cause any major organ toxicity as revealed by gross and histopathologic examination, hematology, blood chemistry, electrocardiograms and urinalysis. The data indicate that in C. apella and M. mulatta, amoscanate is a relatively non-toxic antischistosomal agent effective orally against a broad spectrum of schistosome species.
- Published
- 1983
- Full Text
- View/download PDF
42. Two-year follow-up study of discrimination learning by mentally retarded children.
- Author
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Siegel PS and Crawford KA
- Subjects
- Adolescent, Child, Education of Intellectually Disabled, Feedback, Follow-Up Studies, Humans, Transfer, Psychology, Discrimination Learning, Form Perception, Intellectual Disability psychology, Pattern Recognition, Visual
- Abstract
Mentally retarded children were taught to discriminate the dimensions of a visual display using a matching-to-sample procedure that provided full verbal feedback of the reasons for successes and failures. A control group attempted the matching procedure but received no feedback. The trained subjects exhibited marked superiority in intradimensional transfer. Two years later, the trained subjects continued their advantage but to a lesser degree.
- Published
- 1983
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