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4 Evaluating Plasma GFAP for the Detection of Alzheimer’s Disease Dementia
- Madeline Ally, Henrik Zetterberg, Kaj Blennow, Nicholas J. Ashton, Thomas K. Karikari, Hugo Aparicio, Michael A. Sugarman, Brandon Frank, Yorghos Tripodis, Ann C. McKee, Thor D. Stein, Brett Martin, Joseph N. Palmisano, Eric G. Steinberg, Irene Simkina, Lindsay Farrer, Gyungah Jun, Katherine W. Turk, Andrew E. Budson, Maureen K. O’Connor, Rhoda Au, Wei Qiao Qiu, Lee E. Goldstein, Ronald Killiany, Neil W. Kowall, Robert A. Stern, Jesse Mez, Michael L. Alosco
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 408-409
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Objective:
Blood-based biomarkers represent a scalable and accessible approach for the detection and monitoring of Alzheimer’s disease (AD). Plasma phosphorylated tau (p-tau) and neurofilament light (NfL) are validated biomarkers for the detection of tau and neurodegenerative brain changes in AD, respectively. There is now emphasis to expand beyond these markers to detect and provide insight into the pathophysiological processes of AD. To this end, a reactive astrocytic marker, namely plasma glial fibrillary acidic protein (GFAP), has been of interest. Yet, little is known about the relationship between plasma GFAP and AD. Here, we examined the association between plasma GFAP, diagnostic status, and neuropsychological test performance. Diagnostic accuracy of plasma GFAP was compared with plasma measures of p-tau181 and NfL.
Participants and Methods:This sample included 567 participants from the Boston University (BU) Alzheimer’s Disease Research Center (ADRC) Longitudinal Clinical Core Registry, including individuals with normal cognition (n=234), mild cognitive impairment (MCI) (n=180), and AD dementia (n=153). The sample included all participants who had a blood draw. Participants completed a comprehensive neuropsychological battery (sample sizes across tests varied due to missingness). Diagnoses were adjudicated during multidisciplinary diagnostic consensus conferences. Plasma samples were analyzed using the Simoa platform. Binary logistic regression analyses tested the association between GFAP levels and diagnostic status (i.e., cognitively impaired due to AD versus unimpaired), controlling for age, sex, race, education, and APOE e4 status. Area under the curve (AUC) statistics from receiver operating characteristics (ROC) using predicted probabilities from binary logistic regression examined the ability of plasma GFAP to discriminate diagnostic groups compared with plasma p-tau181 and NfL. Linear regression models tested the association between plasma GFAP and neuropsychological test performance, accounting for the above covariates.
Results:The mean (SD) age of the sample was 74.34 (7.54), 319 (56.3%) were female, 75 (13.2%) were Black, and 223 (39.3%) were APOE e4 carriers. Higher GFAP concentrations were associated with increased odds for having cognitive impairment (GFAP z-score transformed: OR=2.233, 95% CI [1.609, 3.099], p<0.001; non-z-transformed: OR=1.004, 95% CI [1.002, 1.006], p<0.001). ROC analyses, comprising of GFAP and the above covariates, showed plasma GFAP discriminated the cognitively impaired from unimpaired (AUC=0.75) and was similar, but slightly superior, to plasma p-tau181 (AUC=0.74) and plasma NfL (AUC=0.74). A joint panel of the plasma markers had greatest discrimination accuracy (AUC=0.76). Linear regression analyses showed that higher GFAP levels were associated with worse performance on neuropsychological tests assessing global cognition, attention, executive functioning, episodic memory, and language abilities (ps<0.001) as well as higher CDR Sum of Boxes (p<0.001).
Conclusions:Higher plasma GFAP levels differentiated participants with cognitive impairment from those with normal cognition and were associated with worse performance on all neuropsychological tests assessed. GFAP had similar accuracy in detecting those with cognitive impairment compared with p-tau181 and NfL, however, a panel of all three biomarkers was optimal. These results support the utility of plasma GFAP in AD detection and suggest the pathological processes it represents might play an integral role in the pathogenesis of AD.
5 Antemortem Plasma GFAP Predicts Alzheimer’s Disease Neuropathological Changes
- Madeline Ally, Henrik Zetterberg, Kaj Blennow, Nicholas J. Ashton, Thomas K. Karikari, Hugo Aparicio, Michael A. Sugarman, Brandon Frank, Yorghos Tripodis, Brett Martin, Joseph N. Palmisano, Eric G. Steinberg, Irene Simkina, Lindsay Farrer, Gyungah Jun, Katherine W. Turk, Andrew E. Budson, Maureen K. O’Connor, Rhoda Au, Wei Qiao Qiu, Lee E. Goldstein, Ronald Killiany, Neil W. Kowall, Robert A. Stern, Jesse Mez, Bertran R. Huber, Ann C. McKee, Thor D. Stein, Michael L. Alosco
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 409-410
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Objective:
Blood-based biomarkers offer a more feasible alternative to Alzheimer’s disease (AD) detection, management, and study of disease mechanisms than current in vivo measures. Given their novelty, these plasma biomarkers must be assessed against postmortem neuropathological outcomes for validation. Research has shown utility in plasma markers of the proposed AT(N) framework, however recent studies have stressed the importance of expanding this framework to include other pathways. There is promising data supporting the usefulness of plasma glial fibrillary acidic protein (GFAP) in AD, but GFAP-to-autopsy studies are limited. Here, we tested the association between plasma GFAP and AD-related neuropathological outcomes in participants from the Boston University (BU) Alzheimer’s Disease Research Center (ADRC).
Participants and Methods:This sample included 45 participants from the BU ADRC who had a plasma sample within 5 years of death and donated their brain for neuropathological examination. Most recent plasma samples were analyzed using the Simoa platform. Neuropathological examinations followed the National Alzheimer’s Coordinating Center procedures and diagnostic criteria. The NIA-Reagan Institute criteria were used for the neuropathological diagnosis of AD. Measures of GFAP were log-transformed. Binary logistic regression analyses tested the association between GFAP and autopsy-confirmed AD status, as well as with semi-quantitative ratings of regional atrophy (none/mild versus moderate/severe) using binary logistic regression. Ordinal logistic regression analyses tested the association between plasma GFAP and Braak stage and CERAD neuritic plaque score. Area under the curve (AUC) statistics from receiver operating characteristics (ROC) using predicted probabilities from binary logistic regression examined the ability of plasma GFAP to discriminate autopsy-confirmed AD status. All analyses controlled for sex, age at death, years between last blood draw and death, and APOE e4 status.
Results:Of the 45 brain donors, 29 (64.4%) had autopsy-confirmed AD. The mean (SD) age of the sample at the time of blood draw was 80.76 (8.58) and there were 2.80 (1.16) years between the last blood draw and death. The sample included 20 (44.4%) females, 41 (91.1%) were White, and 20 (44.4%) were APOE e4 carriers. Higher GFAP concentrations were associated with increased odds for having autopsy-confirmed AD (OR=14.12, 95% CI [2.00, 99.88], p=0.008). ROC analysis showed plasma GFAP accurately discriminated those with and without autopsy-confirmed AD on its own (AUC=0.75) and strengthened as the above covariates were added to the model (AUC=0.81). Increases in GFAP levels corresponded to increases in Braak stage (OR=2.39, 95% CI [0.71-4.07], p=0.005), but not CERAD ratings (OR=1.24, 95% CI [0.004, 2.49], p=0.051). Higher GFAP levels were associated with greater temporal lobe atrophy (OR=10.27, 95% CI [1.53,69.15], p=0.017), but this was not observed with any other regions.
Conclusions:The current results show that antemortem plasma GFAP is associated with non-specific AD neuropathological changes at autopsy. Plasma GFAP could be a useful and practical biomarker for assisting in the detection of AD-related changes, as well as for study of disease mechanisms.
VistoSeg: Processing utilities for high-resolution images for spatially resolved transcriptomics data
- Madhavi Tippani, Heena R. Divecha, Joseph L. Catallini II, Sang H. Kwon, Lukas M. Weber, Abby Spangler, Andrew E. Jaffe, Thomas M. Hyde, Joel E. Kleinman, Stephanie C. Hicks, Keri Martinowich, Leonardo Collado-Torres, Stephanie C. Page, Kristen R. Maynard
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- Biological Imaging / Volume 3 / 2023
- Published online by Cambridge University Press:
- 13 November 2023, e23
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Spatially resolved transcriptomics (SRT) is a growing field that links gene expression to anatomical context. SRT approaches that use next-generation sequencing (NGS) combine RNA sequencing with histological or fluorescent imaging to generate spatial maps of gene expression in intact tissue sections. These technologies directly couple gene expression measurements with high-resolution histological or immunofluorescent images that contain rich morphological information about the tissue under study. While broad access to NGS-based spatial transcriptomic technology is now commercially available through the Visium platform from the vendor 10× Genomics, computational tools for extracting image-derived metrics for integration with gene expression data remain limited. We developed VistoSeg as a MATLAB pipeline to process, analyze and interactively visualize the high-resolution images generated in the Visium platform. VistoSeg outputs can be easily integrated with accompanying transcriptomic data to facilitate downstream analyses in common programing languages including R and Python. VistoSeg provides user-friendly tools for integrating image-derived metrics from histological and immunofluorescent images with spatially resolved gene expression data. Integration of this data enhances the ability to understand the transcriptional landscape within tissue architecture. VistoSeg is freely available at http://research.libd.org/VistoSeg/.
Decoding neural reactivation of threat during fear learning, extinction, and recall in a randomized clinical trial of L-DOPA among women with PTSD
- Josh M. Cisler, Joseph E. Dunsmoor, Anthony A. Privratsky, G. Andrew James
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- Journal:
- Psychological Medicine / Volume 54 / Issue 6 / April 2024
- Published online by Cambridge University Press:
- 09 October 2023, pp. 1091-1101
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Background
Laboratory paradigms are widely used to study fear learning in posttraumatic stress disorder (PTSD). Recent basic science models demonstrate that, during fear learning, patterns of activity in large neuronal ensembles for the conditioned stimuli (CS) begin to reinstate neural activity patterns for the unconditioned stimuli (US), suggesting a direct way of quantifying fear memory strength for the CS. Here, we translate this concept to human neuroimaging and test the impact of post-learning dopaminergic neurotransmission on fear memory strength during fear acquisition, extinction, and recall among women with PTSD in a re-analysis of previously reported data.
MethodsParticipants (N = 79) completed a context-dependent fear acquisition and extinction task on day 1 and extinction recall tests 24 h later. We decoded activity patterns in large-scale functional networks for the US, then applied this decoder to activity patterns toward the CS on day 1 and day 2.
ResultsUS decoder output for the CS+ increased during acquisition and decreased during extinction in networks traditionally implicated in human fear learning. The strength of US neural reactivation also predicted individuals skin conductance responses. Participants randomized to receive L-DOPA (n = 43) following extinction on day 1 demonstrated less US neural reactivation on day 2 relative to the placebo group (n = 28).
ConclusionThese results support neural reactivation as a measure of memory strength between competing memories of threat and safety and further demonstrate the role of dopaminergic neurotransmission in the consolidation of fear extinction memories.
Choosing with confidence: Self-efficacy and preferences for choice
- Andrew E. Reed, Joseph A. Mikels, Corinna E. Löckenhoff
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- Judgment and Decision Making / Volume 7 / Issue 2 / March 2012
- Published online by Cambridge University Press:
- 01 January 2023, pp. 173-180
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Previous research on the role of choice set size in decision making has focused on decision outcomes and satisfaction. In contrast, little is known about interindividual differences in preferences for larger versus smaller choice sets, let alone the causes of such differences. Drawing on self-efficacy theory, two studies examined the role of decision-making self-efficacy in preferences for choice. Using a correlational approach, Study 1 (n = 89) found that decision-making self-efficacy was positively associated with preferences for choice across a range of consumer decisions. This association was found both between- and within-subjects. Study 2 (n = 65) experimentally manipulated decision-making self-efficacy for an incentive-compatible choice among photo printers. Preferences for choice and pre-choice information seeking were significantly lower in a low-efficacy condition compared to a high-efficacy condition and a control group. Future research directions and implications for decision-making theory and public policy are discussed.
A New Radiocarbon Database for the Lower 48 States
- Robert L. Kelly, Madeline E. Mackie, Erick Robinson, Jack Meyer, Michael Berry, Matthew Boulanger, Brian F. Codding, Jacob Freeman, Carey James Garland, Joseph Gingerich, Robert Hard, James Haug, Andrew Martindale, Scott Meeks, Myles Miller, Shane Miller, Timothy Perttula, Jim A. Railey, Ken Reid, Ian Scharlotta, Jerry Spangler, David Hurst Thomas, Victor Thompson, Andrew White
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- Journal:
- American Antiquity / Volume 87 / Issue 3 / July 2022
- Published online by Cambridge University Press:
- 07 February 2022, pp. 581-590
- Print publication:
- July 2022
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From 2014 to 2020, we compiled radiocarbon ages from the lower 48 states, creating a database of more than 100,000 archaeological, geological, and paleontological ages that will be freely available to researchers through the Canadian Archaeological Radiocarbon Database. Here, we discuss the process used to compile ages, general characteristics of the database, and lessons learned from this exercise in “big data” compilation.
Trust in Government Agencies in the Time of COVID-19
- Scott E. Robinson, Kuhika Gupta, Joseph Ripberger, Jennifer A. Ross, Andrew Fox, Hank Jenkins-Smith, Carol Silva
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- 21 October 2021
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- 11 November 2021
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As the US faced its lowest levels of reported trust in government, the COVID-19 crisis revealed the essential service that various federal agencies provide as sources of information. This Element explores variations in trust across various levels of government and government agencies based on a nationally-representative survey conducted in March of 2020. First, it examines trust in agencies including the Department of Health and Human Services, state health departments, and local health care providers. This includes variation across key characteristics including party identification, age, and race. Second, the Element explores the evolution of trust in health-related organizations throughout 2020 as the pandemic continued. The Element concludes with a discussion of the implications for agency-specific assessments of trust and their importance as we address historically low levels of trust in government. This title is also available as Open Access on Cambridge Core.
Lumateperone (ITI−007) in the Treatment of Bipolar Depression: Results from a Randomized Clinical Trial
- Ian D’Souza, Suresh Durgam, Andrew Satlin, Robert E. Davis, Susan G. Kozauer, Richard Chen, Sharon Mates, Joseph R Calabrese
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- CNS Spectrums / Volume 26 / Issue 2 / April 2021
- Published online by Cambridge University Press:
- 10 May 2021, p. 150
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Study Objective
Approved treatments for bipolar depression are limited and associated with a spectrum of undesirable side effects. Lumateperone (lumateperone tosylate, ITI−007), a mechanistically novel antipsychotic that simultaneously modulates serotonin, dopamine, and glutamate neurotransmission, is FDA-approved for the treatment of schizophrenia. Lumateperone is currently being investigated for the treatment of bipolar depression (major depressive episodes [MDE] associated with bipolar I and bipolar II disorder). This Phase 3 randomized, double-blind, parallel-group, placebo-controlled multinational study (NCT03249376) investigated the efficacy and safety of lumateperone in patients with bipolar I or bipolar II disorder experiencing a MDE.
MethodPatients (18 75 years) with a clinical diagnosis of bipolar I or bipolar II disorder who were experiencing a MDE (Montgomery-Åsberg Depression Rating Scale [MADRS] Total score =20 and a Clinical Global Impression Scale-Bipolar Version-Severity [CGI-BP-S] score =4 at screening and baseline) were randomized to lumateperone 42mg or placebo for 6 weeks. The primary and key secondary efficacy endpoints were change from baseline to Day 43 in MADRS total score and CGI-BP-S scores, respectively. Secondary efficacy outcomes included response (MADRS improvement = 50%) and remission (MADRS total score =12) at Day 43. Safety assessments included treatment emergent adverse events, laboratory parameters, vital signs, extrapyramidal symptoms (EPS), and suicidality.
ResultsIn this study, 377 patients received treatment (placebo, n=189; lumateperone 42mg, n=188) and 333 completed treatment. Patients in the lumateperone 42-mg group had significantly greater mean improvement on MADRS total score change from baseline to Day 43 compared with placebo (least squares mean difference [LSMD]=-4.6; 95% confidence interval [CI]=-6.34, −2.83; effect size vs placebo [ES]=-0.56; P<.0001). Lumateperone treatment was associated with significant MADRS improvement in both patients with bipolar I (LSMD=-4.0; 95% CI=-5.92, −1.99; ES=-0.49; P<.0001) and bipolar II (LSMD=-7.0; 95% CI=-10.92, −3.16; ES=-0.81; P=.0004). The lumateperone 42-mg group also had significantly greater mean improvement in CGI-BP-S total score compared with placebo (LSMD=-0.9; 95% CI=-1.37, −0.51; ES=-0.46; P<.001). Lumateperone compared with placebo had significantly greater MADRS response rate (51.1% vs 36.7%; odds ratio=2.98; P<.001) and remission rates (P=.02) at Day 43. Lumateperone treatment was well tolerated, with minimal risk of EPS, metabolic, and prolactin side effects.
ConclusionsLumateperone 42 mg significantly improved depression symptoms in both patients with bipolar I and bipolar II depression. Lumateperone was generally well tolerated. These results suggest that lumateperone 42 mg may be a promising new treatment for bipolar depression associated with bipolar I or bipolar II disorder.
FundingIntra-Cellular Therapies, Inc.
Septic Shock: A Genomewide Association Study and Polygenic Risk Score Analysis
- Shannon D’Urso, Dorrilyn Rajbhandari, Elizabeth Peach, Erika de Guzman, Qiang Li, Sarah E. Medland, Scott D. Gordon, Nicholas G. Martin, CHARGE Inflammation Working Group, Symen Ligthart, Matthew A. Brown, Joseph Powell, Colin McArthur, Andrew Rhodes, Jason Meyer, Simon Finfer, John Myburgh, Antje Blumenthal, Jeremy Cohen, Balasubramanian Venkatesh, Gabriel Cuellar-Partida, David M. Evans
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- Journal:
- Twin Research and Human Genetics / Volume 23 / Issue 4 / August 2020
- Published online by Cambridge University Press:
- 05 August 2020, pp. 204-213
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Previous genetic association studies have failed to identify loci robustly associated with sepsis, and there have been no published genetic association studies or polygenic risk score analyses of patients with septic shock, despite evidence suggesting genetic factors may be involved. We systematically collected genotype and clinical outcome data in the context of a randomized controlled trial from patients with septic shock to enrich the presence of disease-associated genetic variants. We performed genomewide association studies of susceptibility and mortality in septic shock using 493 patients with septic shock and 2442 population controls, and polygenic risk score analysis to assess genetic overlap between septic shock risk/mortality with clinically relevant traits. One variant, rs9489328, located in AL589740.1 noncoding RNA, was significantly associated with septic shock (p = 1.05 × 10–10); however, it is likely a false-positive. We were unable to replicate variants previously reported to be associated (p < 1.00 × 10–6 in previous scans) with susceptibility to and mortality from sepsis. Polygenic risk scores for hematocrit and granulocyte count were negatively associated with 28-day mortality (p = 3.04 × 10–3; p = 2.29 × 10–3), and scores for C-reactive protein levels were positively associated with susceptibility to septic shock (p = 1.44 × 10–3). Results suggest that common variants of large effect do not influence septic shock susceptibility, mortality and resolution; however, genetic predispositions to clinically relevant traits are significantly associated with increased susceptibility and mortality in septic individuals.
The 4D Camera: Very High Speed Electron Counting for 4D-STEM
- Jim Ciston, Ian J. Johnson, Brent R. Draney, Peter Ercius, Erin Fong, Azriel Goldschmidt, John M. Joseph, Jason R. Lee, Alexander Mueller, Colin Ophus, Ashwin Selvarajan, David E. Skinner, Thorsten Stezelberger, Craig S. Tindall, Andrew M. Minor, Peter Denes
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- Journal:
- Microscopy and Microanalysis / Volume 25 / Issue S2 / August 2019
- Published online by Cambridge University Press:
- 05 August 2019, pp. 1930-1931
- Print publication:
- August 2019
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The Comprehensive Assessment of Neurodegeneration and Dementia: Canadian Cohort Study
- Howard Chertkow, Michael Borrie, Victor Whitehead, Sandra E. Black, Howard H. Feldman, Serge Gauthier, David B. Hogan, Mario Masellis, Katherine McGilton, Kenneth Rockwood, Mary C. Tierney, Melissa Andrew, Ging-Yuek R. Hsiung, Richard Camicioli, Eric E. Smith, Jennifer Fogarty, Joseph Lindsay, Sarah Best, Alan Evans, Samir Das, Zia Mohaddes, Randi Pilon, Judes Poirier, Natalie A. Phillips, Elizabeth MacNamara, Roger A. Dixon, Simon Duchesne, Ian MacKenzie, R. Jane Rylett
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- Journal:
- Canadian Journal of Neurological Sciences / Volume 46 / Issue 5 / September 2019
- Published online by Cambridge University Press:
- 16 July 2019, pp. 499-511
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Background:
The Comprehensive Assessment of Neurodegeneration and Dementia (COMPASS-ND) cohort study of the Canadian Consortium on Neurodegeneration in Aging (CCNA) is a national initiative to catalyze research on dementia, set up to support the research agendas of CCNA teams. This cross-country longitudinal cohort of 2310 deeply phenotyped subjects with various forms of dementia and mild memory loss or concerns, along with cognitively intact elderly subjects, will test hypotheses generated by these teams.
Methods:The COMPASS-ND protocol, initial grant proposal for funding, fifth semi-annual CCNA Progress Report submitted to the Canadian Institutes of Health Research December 2017, and other documents supplemented by modifications made and lessons learned after implementation were used by the authors to create the description of the study provided here.
Results:The CCNA COMPASS-ND cohort includes participants from across Canada with various cognitive conditions associated with or at risk of neurodegenerative diseases. They will undergo a wide range of experimental, clinical, imaging, and genetic investigation to specifically address the causes, diagnosis, treatment, and prevention of these conditions in the aging population. Data derived from clinical and cognitive assessments, biospecimens, brain imaging, genetics, and brain donations will be used to test hypotheses generated by CCNA research teams and other Canadian researchers. The study is the most comprehensive and ambitious Canadian study of dementia. Initial data posting occurred in 2018, with the full cohort to be accrued by 2020.
Conclusion:Availability of data from the COMPASS-ND study will provide a major stimulus for dementia research in Canada in the coming years.
Correlation between white blood cell count and mood-stabilising treatment response in two bipolar disorder trials
- Ole Köhler-Forsberg, Louisa G. Sylvia, Charles L. Bowden, Joseph R. Calabrese, Michael E. Thase, Richard C. Shelton, Melvin McInnis, Mauricio Tohen, James H. Kocsis, Terence A. Ketter, Edward S. Friedman, Thilo Deckersbach, Michael J. Ostacher, Dan V. Iosifescu, Susan McElroy, Andrew A. Nierenberg
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- Acta Neuropsychiatrica / Volume 31 / Issue 4 / August 2019
- Published online by Cambridge University Press:
- 06 June 2019, pp. 230-234
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Background:
Immune system markers may predict affective disorder treatment response, but whether an overall immune system marker predicts bipolar disorder treatment effect is unclear.
Methods:Bipolar CHOICE (N = 482) and LiTMUS (N = 283) were similar comparative effectiveness trials treating patients with bipolar disorder for 24 weeks with four different treatment arms (standard-dose lithium, quetiapine, moderate-dose lithium plus optimised personalised treatment (OPT) and OPT without lithium). We performed secondary mixed effects linear regression analyses adjusted for age, gender, smoking and body mass index to investigate relationships between pre-treatment white blood cell (WBC) levels and clinical global impression scale (CGI) response.
Results:Compared to participants with WBC counts of 4.5–10 × 109/l, participants with WBC < 4.5 or WBC ≥ 10 showed similar improvement within each specific treatment arm and in gender-stratified analyses.
Conclusions:An overall immune system marker did not predict differential treatment response to four different treatment approaches for bipolar disorder all lasting 24 weeks.
3265 Analysis of High-Dimensional Patient Data in Characterizing Alzheimer’s Disease Progression
- Daniel Baer, Andrew B. Lawson, Brandon Vaughan, Jane E. Joseph
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- Journal:
- Journal of Clinical and Translational Science / Volume 3 / Issue s1 / March 2019
- Published online by Cambridge University Press:
- 26 March 2019, p. 3
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OBJECTIVES/SPECIFIC AIMS: Our research hypothesis is that resting state fMRI (rsfMRI) data can be used to identify regions of the brain which are associated with cognitive decline in patients – thereby providing a tool by which to characterize AD progression in patients. METHODS/STUDY POPULATION: We used data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) to analyze Mini-Mental State Examination (MMSE) questionnaire scores from 14 patients diagnosed with AD at two measurement occasions. RsfMRI data was available at the first of these occasions for these patients. These rsfMRI data were summarized into 264 node-based graph theory measures of clustering coefficient and eigenvector centrality. To address our research hypothesis, we modeled changes in patient MMSE scores over time as a function of these rsfMRI data, controlling for relevant confounding factors. This model accounted for the high-dimensionality of our predictor data, the longitudinal nature of the outcome, and our desire to identify a subset of regions in the brain most associated with the MMSE outcome. RESULTS/ANTICIPATED RESULTS: The use of either the clustering coefficient or eigenvector centrality rsfMRI predictors in modeling MMSE scores for patients over time resulted in the identification of different subsets of brain regions associated with cognitive decline. This suggests that these predictors capture different information on patient propensity for cognitive decline. Further work is warranted to validate these results on a larger sample of ADNI patients. DISCUSSION/SIGNIFICANCE OF IMPACT: We conclude that different rsfMRI graph theory measures capture different aspects of cognitive function and decline in patients, which could be a future consideration in clinical practice.
Delivery of the research participant perception survey through the patient portal
- Issis J. Kelly-Pumarol, Perrin Q. Henderson, Julia T. Rushing, Joseph E. Andrews, Rhonda G. Kost, Lynne E. Wagenknecht
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- Journal:
- Journal of Clinical and Translational Science / Volume 2 / Issue 3 / June 2018
- Published online by Cambridge University Press:
- 21 September 2018, pp. 163-168
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Introduction
The patient portal may be an effective method for administering surveys regarding participant research experiences but has not been systematically studied.
MethodsWe evaluated 4 methods of delivering a research participant perception survey: mailing, phone, email, and patient portal. Participants of research studies were identified (n=4013) and 800 were randomly selected to receive a survey, 200 for each method. Outcomes included response rate, survey completeness, and cost.
ResultsAmong those aged <65 years, response rates did not differ between mail, phone, and patient portal (22%, 29%, 30%, p>0.07). Among these methods, the patient portal was the lowest-cost option. Response rates were significantly lower using email (10%, p<0.01), the lowest-cost option. In contrast, among those aged 65+ years, mail was superior to the electronic methods (p<0.02).
ConclusionsThe patient portal was among the most effective ways to reach research participants, and was less expensive than surveys administered by mail or telephone.
A Next Generation Electron Microscopy Detector Aimed at Enabling New Scanning Diffraction Techniques and Online Data Reconstruction
- Ian J. Johnson, Karen C. Bustillo, Jim Ciston, Brent R. Draney, Peter Ercius, Erin Fong, Azriel Goldschmidt, John M. Joseph, Jason R. Lee, Andrew M. Minor, Colin Ophus, Ashwin Selvarajan, David E. Skinner, Thorsten Stezelberger, Craig S. Tindall, Peter Denes
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- Journal:
- Microscopy and Microanalysis / Volume 24 / Issue S1 / August 2018
- Published online by Cambridge University Press:
- 01 August 2018, pp. 166-167
- Print publication:
- August 2018
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Disease and Non-Battle Traumatic Injuries Evaluated by Emergency Physicians in a US Tertiary Combat Hospital
- Vikhyat S. Bebarta, Alejandra G. Mora, Patrick C. Ng, Phillip E. Mason, Andrew Muck, Joseph K. Maddry
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- Journal:
- Prehospital and Disaster Medicine / Volume 33 / Issue 1 / February 2018
- Published online by Cambridge University Press:
- 13 December 2017, pp. 53-57
- Print publication:
- February 2018
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Introduction
Analysis of injuries during military operations has focused on those related to combat. Non-combat complaints have received less attention, despite the need for many troops to be evacuated for non-battle illnesses in Iraq. This study aims to further characterize the disease and non-battle injuries (DNBIs) seen at a tertiary combat hospital and to describe the types of procedures and medications used in the management of these cases.
MethodsIn this observational study, patients were enrolled from a convenience sample with non-combat-related diseases and injuries who were evaluated in the emergency department (ED) of a US military tertiary hospital in Iraq from 2007-2008. The treating emergency physician (EP) used a data collection form to enroll patients that arrived to the ED whose injury or illness was unrelated to combat.
ResultsData were gathered on 1,745 patients with a median age of 30 years; 84% of patients were male and 85% were US military personnel. The most common diagnoses evaluated in the ED were abdominal disorders, orthopedic injuries, and headache. Many cases involved intravenous access, laboratory testing, and radiographic testing. Procedures performed included electrocardiogram, lumbar puncture, and intubation.
ConclusionDisease and non-battle traumatic injuries are common in a tertiary combat hospital. Emergency providers working in austere settings should have the diagnostic and procedural skills to evaluate and treat DNBIs.
,Bebarta VS ,Mora AG ,Ng PC ,Mason PE ,Muck A .Maddry JK Disease and Non-Battle Traumatic Injuries Evaluated by Emergency Physicians in a US Tertiary Combat Hospital . Prehosp Disaster Med.2018 ;33 (1 ):53 –57 .
The Last Interglacial Ocean
- Rose Marie L. Cline, James D. Hays, Warren L. Prell, William F. Ruddiman, Ted C. Moore, Nilva G. Kipp, Barbara E. Molfino, George H. Denton, Terence J. Hughes, William L. Balsam, Charlotte A. Brunner, Jean-Claude Duplessy, Ann G. Esmay, James L. Fastook, John Imbrie, Lloyd D. Keigwin, Thomas B. Kellogg, Andrew McIntyre, Robley K. Matthews, Alan C. Mix, Joseph J. Morley, Nicholas J. Shackleton, S. Stephen Streeter, Peter R. Thompson
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- Quaternary Research / Volume 21 / Issue 2 / February 1984
- Published online by Cambridge University Press:
- 20 January 2017, pp. 123-224
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The final effort of the CLIMAP project was a study of the last interglaciation, a time of minimum ice volume some 122,000 yr ago coincident with the Substage 5e oxygen isotopic minimum. Based on detailed oxygen isotope analyses and biotic census counts in 52 cores across the world ocean, last interglacial sea-surface temperatures (SST) were compared with those today. There are small SST departures in the mid-latitude North Atlantic (warmer) and the Gulf of Mexico (cooler). The eastern boundary currents of the South Atlantic and Pacific oceans are marked by large SST anomalies in individual cores, but their interpretations are precluded by no-analog problems and by discordancies among estimates from different biotic groups. In general, the last interglacial ocean was not significantly different from the modern ocean. The relative sequencing of ice decay versus oceanic warming on the Stage 6/5 oxygen isotopic transition and of ice growth versus oceanic cooling on the Stage 5e/5d transition was also studied. In most of the Southern Hemisphere, the oceanic response marked by the biotic census counts preceded (led) the global ice-volume response marked by the oxygen-isotope signal by several thousand years. The reverse pattern is evident in the North Atlantic Ocean and the Gulf of Mexico, where the oceanic response lagged that of global ice volume by several thousand years. As a result, the very warm temperatures associated with the last interglaciation were regionally diachronous by several thousand years. These regional lead-lag relationships agree with those observed on other transitions and in long-term phase relationships; they cannot be explained simply as artifacts of bioturbational translations of the original signals.
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- By Mitchell Aboulafia, Frederick Adams, Marilyn McCord Adams, Robert M. Adams, Laird Addis, James W. Allard, David Allison, William P. Alston, Karl Ameriks, C. Anthony Anderson, David Leech Anderson, Lanier Anderson, Roger Ariew, David Armstrong, Denis G. Arnold, E. J. Ashworth, Margaret Atherton, Robin Attfield, Bruce Aune, Edward Wilson Averill, Jody Azzouni, Kent Bach, Andrew Bailey, Lynne Rudder Baker, Thomas R. Baldwin, Jon Barwise, George Bealer, William Bechtel, Lawrence C. Becker, Mark A. Bedau, Ernst Behler, José A. Benardete, Ermanno Bencivenga, Jan Berg, Michael Bergmann, Robert L. Bernasconi, Sven Bernecker, Bernard Berofsky, Rod Bertolet, Charles J. Beyer, Christian Beyer, Joseph Bien, Joseph Bien, Peg Birmingham, Ivan Boh, James Bohman, Daniel Bonevac, Laurence BonJour, William J. Bouwsma, Raymond D. Bradley, Myles Brand, Richard B. Brandt, Michael E. Bratman, Stephen E. Braude, Daniel Breazeale, Angela Breitenbach, Jason Bridges, David O. Brink, Gordon G. Brittan, Justin Broackes, Dan W. Brock, Aaron Bronfman, Jeffrey E. Brower, Bartosz Brozek, Anthony Brueckner, Jeffrey Bub, Lara Buchak, Otavio Bueno, Ann E. Bumpus, Robert W. Burch, John Burgess, Arthur W. Burks, Panayot Butchvarov, Robert E. Butts, Marina Bykova, Patrick Byrne, David Carr, Noël Carroll, Edward S. Casey, Victor Caston, Victor Caston, Albert Casullo, Robert L. Causey, Alan K. L. Chan, Ruth Chang, Deen K. Chatterjee, Andrew Chignell, Roderick M. Chisholm, Kelly J. Clark, E. J. Coffman, Robin Collins, Brian P. Copenhaver, John Corcoran, John Cottingham, Roger Crisp, Frederick J. Crosson, Antonio S. Cua, Phillip D. Cummins, Martin Curd, Adam Cureton, Andrew Cutrofello, Stephen Darwall, Paul Sheldon Davies, Wayne A. Davis, Timothy Joseph Day, Claudio de Almeida, Mario De Caro, Mario De Caro, John Deigh, C. F. Delaney, Daniel C. Dennett, Michael R. DePaul, Michael Detlefsen, Daniel Trent Devereux, Philip E. Devine, John M. Dillon, Martin C. Dillon, Robert DiSalle, Mary Domski, Alan Donagan, Paul Draper, Fred Dretske, Mircea Dumitru, Wilhelm Dupré, Gerald Dworkin, John Earman, Ellery Eells, Catherine Z. Elgin, Berent Enç, Ronald P. Endicott, Edward Erwin, John Etchemendy, C. Stephen Evans, Susan L. Feagin, Solomon Feferman, Richard Feldman, Arthur Fine, Maurice A. Finocchiaro, William FitzPatrick, Richard E. Flathman, Gvozden Flego, Richard Foley, Graeme Forbes, Rainer Forst, Malcolm R. Forster, Daniel Fouke, Patrick Francken, Samuel Freeman, Elizabeth Fricker, Miranda Fricker, Michael Friedman, Michael Fuerstein, Richard A. Fumerton, Alan Gabbey, Pieranna Garavaso, Daniel Garber, Jorge L. A. Garcia, Robert K. Garcia, Don Garrett, Philip Gasper, Gerald Gaus, Berys Gaut, Bernard Gert, Roger F. Gibson, Cody Gilmore, Carl Ginet, Alan H. Goldman, Alvin I. Goldman, Alfonso Gömez-Lobo, Lenn E. Goodman, Robert M. Gordon, Stefan Gosepath, Jorge J. E. Gracia, Daniel W. Graham, George A. Graham, Peter J. Graham, Richard E. Grandy, I. Grattan-Guinness, John Greco, Philip T. Grier, Nicholas Griffin, Nicholas Griffin, David A. Griffiths, Paul J. Griffiths, Stephen R. Grimm, Charles L. Griswold, Charles B. Guignon, Pete A. Y. Gunter, Dimitri Gutas, Gary Gutting, Paul Guyer, Kwame Gyekye, Oscar A. Haac, Raul Hakli, Raul Hakli, Michael Hallett, Edward C. Halper, Jean Hampton, R. James Hankinson, K. R. Hanley, Russell Hardin, Robert M. Harnish, William Harper, David Harrah, Kevin Hart, Ali Hasan, William Hasker, John Haugeland, Roger Hausheer, William Heald, Peter Heath, Richard Heck, John F. Heil, Vincent F. Hendricks, Stephen Hetherington, Francis Heylighen, Kathleen Marie Higgins, Risto Hilpinen, Harold T. Hodes, Joshua Hoffman, Alan Holland, Robert L. Holmes, Richard Holton, Brad W. Hooker, Terence E. Horgan, Tamara Horowitz, Paul Horwich, Vittorio Hösle, Paul Hoβfeld, Daniel Howard-Snyder, Frances Howard-Snyder, Anne Hudson, Deal W. Hudson, Carl A. Huffman, David L. Hull, Patricia Huntington, Thomas Hurka, Paul Hurley, Rosalind Hursthouse, Guillermo Hurtado, Ronald E. Hustwit, Sarah Hutton, Jonathan Jenkins Ichikawa, Harry A. Ide, David Ingram, Philip J. Ivanhoe, Alfred L. Ivry, Frank Jackson, Dale Jacquette, Joseph Jedwab, Richard Jeffrey, David Alan Johnson, Edward Johnson, Mark D. Jordan, Richard Joyce, Hwa Yol Jung, Robert Hillary Kane, Tomis Kapitan, Jacquelyn Ann K. Kegley, James A. Keller, Ralph Kennedy, Sergei Khoruzhii, Jaegwon Kim, Yersu Kim, Nathan L. King, Patricia Kitcher, Peter D. Klein, E. D. Klemke, Virginia Klenk, George L. Kline, Christian Klotz, Simo Knuuttila, Joseph J. Kockelmans, Konstantin Kolenda, Sebastian Tomasz Kołodziejczyk, Isaac Kramnick, Richard Kraut, Fred Kroon, Manfred Kuehn, Steven T. Kuhn, Henry E. Kyburg, John Lachs, Jennifer Lackey, Stephen E. Lahey, Andrea Lavazza, Thomas H. Leahey, Joo Heung Lee, Keith Lehrer, Dorothy Leland, Noah M. Lemos, Ernest LePore, Sarah-Jane Leslie, Isaac Levi, Andrew Levine, Alan E. Lewis, Daniel E. Little, Shu-hsien Liu, Shu-hsien Liu, Alan K. L. Chan, Brian Loar, Lawrence B. Lombard, John Longeway, Dominic McIver Lopes, Michael J. Loux, E. J. Lowe, Steven Luper, Eugene C. Luschei, William G. Lycan, David Lyons, David Macarthur, Danielle Macbeth, Scott MacDonald, Jacob L. Mackey, Louis H. Mackey, Penelope Mackie, Edward H. Madden, Penelope Maddy, G. B. Madison, Bernd Magnus, Pekka Mäkelä, Rudolf A. Makkreel, David Manley, William E. Mann (W.E.M.), Vladimir Marchenkov, Peter Markie, Jean-Pierre Marquis, Ausonio Marras, Mike W. Martin, A. P. Martinich, William L. McBride, David McCabe, Storrs McCall, Hugh J. McCann, Robert N. McCauley, John J. McDermott, Sarah McGrath, Ralph McInerny, Daniel J. McKaughan, Thomas McKay, Michael McKinsey, Brian P. McLaughlin, Ernan McMullin, Anthonie Meijers, Jack W. Meiland, William Jason Melanson, Alfred R. Mele, Joseph R. Mendola, Christopher Menzel, Michael J. Meyer, Christian B. Miller, David W. Miller, Peter Millican, Robert N. Minor, Phillip Mitsis, James A. Montmarquet, Michael S. Moore, Tim Moore, Benjamin Morison, Donald R. Morrison, Stephen J. Morse, Paul K. Moser, Alexander P. D. Mourelatos, Ian Mueller, James Bernard Murphy, Mark C. Murphy, Steven Nadler, Jan Narveson, Alan Nelson, Jerome Neu, Samuel Newlands, Kai Nielsen, Ilkka Niiniluoto, Carlos G. Noreña, Calvin G. Normore, David Fate Norton, Nikolaj Nottelmann, Donald Nute, David S. Oderberg, Steve Odin, Michael O’Rourke, Willard G. Oxtoby, Heinz Paetzold, George S. Pappas, Anthony J. Parel, Lydia Patton, R. P. Peerenboom, Francis Jeffry Pelletier, Adriaan T. Peperzak, Derk Pereboom, Jaroslav Peregrin, Glen Pettigrove, Philip Pettit, Edmund L. Pincoffs, Andrew Pinsent, Robert B. Pippin, Alvin Plantinga, Louis P. Pojman, Richard H. Popkin, John F. Post, Carl J. Posy, William J. Prior, Richard Purtill, Michael Quante, Philip L. Quinn, Philip L. Quinn, Elizabeth S. Radcliffe, Diana Raffman, Gerard Raulet, Stephen L. Read, Andrews Reath, Andrew Reisner, Nicholas Rescher, Henry S. Richardson, Robert C. Richardson, Thomas Ricketts, Wayne D. Riggs, Mark Roberts, Robert C. Roberts, Luke Robinson, Alexander Rosenberg, Gary Rosenkranz, Bernice Glatzer Rosenthal, Adina L. Roskies, William L. Rowe, T. M. Rudavsky, Michael Ruse, Bruce Russell, Lilly-Marlene Russow, Dan Ryder, R. M. Sainsbury, Joseph Salerno, Nathan Salmon, Wesley C. Salmon, Constantine Sandis, David H. Sanford, Marco Santambrogio, David Sapire, Ruth A. Saunders, Geoffrey Sayre-McCord, Charles Sayward, James P. Scanlan, Richard Schacht, Tamar Schapiro, Frederick F. Schmitt, Jerome B. Schneewind, Calvin O. Schrag, Alan D. Schrift, George F. Schumm, Jean-Loup Seban, David N. Sedley, Kenneth Seeskin, Krister Segerberg, Charlene Haddock Seigfried, Dennis M. Senchuk, James F. Sennett, William Lad Sessions, Stewart Shapiro, Tommie Shelby, Donald W. Sherburne, Christopher Shields, Roger A. Shiner, Sydney Shoemaker, Robert K. Shope, Kwong-loi Shun, Wilfried Sieg, A. John Simmons, Robert L. Simon, Marcus G. Singer, Georgette Sinkler, Walter Sinnott-Armstrong, Matti T. Sintonen, Lawrence Sklar, Brian Skyrms, Robert C. Sleigh, Michael Anthony Slote, Hans Sluga, Barry Smith, Michael Smith, Robin Smith, Robert Sokolowski, Robert C. Solomon, Marta Soniewicka, Philip Soper, Ernest Sosa, Nicholas Southwood, Paul Vincent Spade, T. L. S. Sprigge, Eric O. Springsted, George J. Stack, Rebecca Stangl, Jason Stanley, Florian Steinberger, Sören Stenlund, Christopher Stephens, James P. Sterba, Josef Stern, Matthias Steup, M. A. Stewart, Leopold Stubenberg, Edith Dudley Sulla, Frederick Suppe, Jere Paul Surber, David George Sussman, Sigrún Svavarsdóttir, Zeno G. Swijtink, Richard Swinburne, Charles C. Taliaferro, Robert B. Talisse, John Tasioulas, Paul Teller, Larry S. Temkin, Mark Textor, H. S. Thayer, Peter Thielke, Alan Thomas, Amie L. Thomasson, Katherine Thomson-Jones, Joshua C. Thurow, Vzalerie Tiberius, Terrence N. Tice, Paul Tidman, Mark C. Timmons, William Tolhurst, James E. Tomberlin, Rosemarie Tong, Lawrence Torcello, Kelly Trogdon, J. D. Trout, Robert E. Tully, Raimo Tuomela, John Turri, Martin M. Tweedale, Thomas Uebel, Jennifer Uleman, James Van Cleve, Harry van der Linden, Peter van Inwagen, Bryan W. Van Norden, René van Woudenberg, Donald Phillip Verene, Samantha Vice, Thomas Vinci, Donald Wayne Viney, Barbara Von Eckardt, Peter B. M. Vranas, Steven J. Wagner, William J. Wainwright, Paul E. Walker, Robert E. Wall, Craig Walton, Douglas Walton, Eric Watkins, Richard A. Watson, Michael V. Wedin, Rudolph H. Weingartner, Paul Weirich, Paul J. Weithman, Carl Wellman, Howard Wettstein, Samuel C. Wheeler, Stephen A. White, Jennifer Whiting, Edward R. Wierenga, Michael Williams, Fred Wilson, W. Kent Wilson, Kenneth P. Winkler, John F. Wippel, Jan Woleński, Allan B. Wolter, Nicholas P. Wolterstorff, Rega Wood, W. Jay Wood, Paul Woodruff, Alison Wylie, Gideon Yaffe, Takashi Yagisawa, Yutaka Yamamoto, Keith E. Yandell, Xiaomei Yang, Dean Zimmerman, Günter Zoller, Catherine Zuckert, Michael Zuckert, Jack A. Zupko (J.A.Z.)
- Edited by Robert Audi, University of Notre Dame, Indiana
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- The Cambridge Dictionary of Philosophy
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- 05 August 2015
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- 27 April 2015, pp ix-xxx
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- By Andrew Adesman, Lenard A. Adler, Samuel Alperin, Kira E. Armstrong, L. Eugene Arnold, Amy F. T. Arnsten, Russell A. Barkley, Craig W. Berridge, Joseph Biederman, F. Xavier Castellanos, Barbara J. Coffey, Alison M. Cohn, C. Keith Conners, Joan M. Daughton, Stephen V. Faraone, John Fayyad, Lisa G. Hahn, Laura Hans, Elizabeth Hurt, Gagan Joshi, Rahil Jummani, Jesse M. Jun, Ronald C. Kessler, Scott Haden Kollins, Kimberly Kovacs, Christopher J. Kratochvil, Beth Krone, Nicholas Lofthouse, Michael J. Manos, Francis Joseph McClernon, Joel E. Morgan, Nicholas R. Morrison, Sonali Nanayakkara, Jeffrey H. Newcorn, Phillip L. Pearl, Juan D. Pedraza, Guy M. L. Perry, Steven R. Pliszka, Jefferson B. Prince, J. Russell Ramsay, Anthony L. Rostain, David M. Shaw, Mary V. Solanto, Mark A. Stein, Jonathan R. Stevens, Brigette S. Vaughan, Margaret Weiss, Roy E. Weiss, Timothy E. Wilens, Janet Wozniak
- Edited by Lenard A. Adler, New York University School of Medicine, Thomas J. Spencer, Timothy E. Wilens
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- Attention-Deficit Hyperactivity Disorder in Adults and Children
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- 05 February 2015
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- 08 January 2015, pp vii-x
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