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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.
A causal roadmap for generating high-quality real-world evidence
- Lauren E. Dang, Susan Gruber, Hana Lee, Issa J. Dahabreh, Elizabeth A. Stuart, Brian D. Williamson, Richard Wyss, Iván Díaz, Debashis Ghosh, Emre Kıcıman, Demissie Alemayehu, Katherine L. Hoffman, Carla Y. Vossen, Raymond A. Huml, Henrik Ravn, Kajsa Kvist, Richard Pratley, Mei-Chiung Shih, Gene Pennello, David Martin, Salina P. Waddy, Charles E. Barr, Mouna Akacha, John B. Buse, Mark van der Laan, Maya Petersen
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- Journal of Clinical and Translational Science / Volume 7 / Issue 1 / 2023
- Published online by Cambridge University Press:
- 22 September 2023, e212
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Increasing emphasis on the use of real-world evidence (RWE) to support clinical policy and regulatory decision-making has led to a proliferation of guidance, advice, and frameworks from regulatory agencies, academia, professional societies, and industry. A broad spectrum of studies use real-world data (RWD) to produce RWE, ranging from randomized trials with outcomes assessed using RWD to fully observational studies. Yet, many proposals for generating RWE lack sufficient detail, and many analyses of RWD suffer from implausible assumptions, other methodological flaws, or inappropriate interpretations. The Causal Roadmap is an explicit, itemized, iterative process that guides investigators to prespecify study design and analysis plans; it addresses a wide range of guidance within a single framework. By supporting the transparent evaluation of causal assumptions and facilitating objective comparisons of design and analysis choices based on prespecified criteria, the Roadmap can help investigators to evaluate the quality of evidence that a given study is likely to produce, specify a study to generate high-quality RWE, and communicate effectively with regulatory agencies and other stakeholders. This paper aims to disseminate and extend the Causal Roadmap framework for use by clinical and translational researchers; three companion papers demonstrate applications of the Causal Roadmap for specific use cases.
426 Datathon Revisited: Implementation of Lesson Learned
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- Andrew J. Zimolzak, Katherine Sippel, Jessica A. Davila, Michael E. DeBakey, Vamshi Punugoti, Paul E. Klotman, Laura A. Petersen, Michael E. DeBakey, Gloria Liao, Lee Leiber, Christopher I. Amos
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- Journal of Clinical and Translational Science / Volume 7 / Issue s1 / April 2023
- Published online by Cambridge University Press:
- 24 April 2023, pp. 127-128
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OBJECTIVES/GOALS: In 2020, Baylor College of Medicine held a datathon to introduce a data warehouse, identify its capabilities/limitations, foster collaborations, and engage trainees. The event was held again in 2022, and lessons learned (e.g., tools for data self-service or team communication) were applied. METHODS/STUDY POPULATION: Senior faculty reviewed proposals with an emphasis on feasibility, impact, and relevance to quality improvement or population health. Selected teams worked with Information Technology (IT) for 2 months and presented findings at a 1-day event. Surveys were administered to participants before and after the event to evaluate their background, team characteristics, collaborations, knowledge before and after the datathon, perceived value of the datathon, and plans for future work. Descriptive statistics of respondents’ self-reports were tabulated. RESULTS/ANTICIPATED RESULTS: In 2022, 19 of 36 projects were accepted (13/33 in 2020). At both events, most projects studied quality improvement or clinical outcomes. Of 82 participants in 2022, 54 completed surveys. In 2022, 72% had no datathon experience (48% in 2020). Median effort was 10 person-hours; median IT time was 20% (20 and 10%, in 2020). Seven respondents finished and 21 partially finished their projects (1 and 11, in 2020); 92% made new collaborations (91% in 2020). Respondents strongly agreed that: the experience was valuable (n=28), they would participate in future datathons (n=30), and they would use the warehouse for future work (n=25). Twenty-seven have planned abstracts; 25 have planned manuscripts. DISCUSSION/SIGNIFICANCE: The 2022 datathon had more participants with less experience, potentially due to improved promotion and training opportunities. Fewer person-hours and a higher percentage of IT time were required as compared to 2020, and more projects were completed, possibly due to increased IT efficiency.
GASKAP-HI Pilot Survey Science III: An unbiased view of cold gas in the Small Magellanic Cloud
- James Dempsey, N. M. McClure-Griffiths, Claire Murray, John M. Dickey, Nickolas M. Pingel, Katherine Jameson, Helga Dénes, Jacco Th. van Loon, D. Leahy, Min-Young Lee, S. Stanimirović, Shari Breen, Frances Buckland-Willis, Steven J. Gibson, Hiroshi Imai, Callum Lynn, C. D. Tremblay
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- Publications of the Astronomical Society of Australia / Volume 39 / 2022
- Published online by Cambridge University Press:
- 05 August 2022, e034
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We present the first unbiased survey of neutral hydrogen absorption in the Small Magellanic Cloud. The survey utilises pilot neutral hydrogen observations with the Australian Square Kilometre Array Pathfinder telescope as part of the Galactic Australian Square Kilometre Array Pathfinder neutral hydrogen project whose dataset has been processed with the Galactic Australian Square Kilometre Array Pathfinder-HI absorption pipeline, also described here. This dataset provides absorption spectra towards 229 continuum sources, a 275% increase in the number of continuum sources previously published in the Small Magellanic Cloud region, as well as an improvement in the quality of absorption spectra over previous surveys of the Small Magellanic Cloud. Our unbiased view, combined with the closely matched beam size between emission and absorption, reveals a lower cold gas faction (11%) than the 2019 ATCA survey of the Small Magellanic Cloud and is more representative of the Small Magellanic Cloud as a whole. We also find that the optical depth varies greatly between the Small Magellanic Cloud’s bar and wing regions. In the bar we find that the optical depth is generally low (correction factor to the optically thin column density assumption of $\mathcal{R}_{\mathrm{HI}} \sim 1.04$ ) but increases linearly with column density. In the wing however, there is a wide scatter in optical depth despite a tighter range of column densities.
Mental health in young adults born extremely preterm or extremely low birthweight with contemporary neonatal intensive care
- Alice C. Burnett, Rheanna M. Mainzer, Lex W. Doyle, Katherine J. Lee, Peter J. Anderson, Diana Zannino, Julianne Duff, George C. Patton, Jeanie L. Y. Cheong, for the Victorian Infant Collaborative Study Group
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- Psychological Medicine / Volume 53 / Issue 11 / August 2023
- Published online by Cambridge University Press:
- 22 July 2022, pp. 5227-5234
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Background
For infants born in the contemporary era of neonatal care, little is known about adult mental health outcomes of extremely preterm birth (EP; <28 weeks' gestation) or extremely low birthweight (ELBW; <1000 g). This study aimed to compare attention deficit hyperactivity disorder (ADHD), anxiety, mood, and substance use disorder prevalence in young adults born EP/ELBW and normal birthweight (NBW; >2499 g) controls, and to compare change in prevalence of mental health symptoms and disorders from 18 to 25 years.
MethodsParticipants were a prospective geographical cohort of 297 consecutive survivors born EP/ELBW during 1991–1992 and 260 NBW controls. At age 25 years, 174 EP/ELBW and 139 NBW participants completed the Adult ADHD Rating Scale, Structured Clinical Interview for DSM-IV Disorders, Beck Anxiety Inventory, and Center for Epidemiologic Studies Depression Scale-Revised. Data from follow-up at 18 years were also utilized. Multiple imputation was used to account for attrition.
ResultsMental health outcomes at 25 years were similar between groups: prevalence rates were ADHD 7% v. 5%; anxiety 32% v. 27%; mood 38% v. 35%; substance use 12% v. 14% in the EP/ELBW and NBW groups, respectively. In both groups, ADHD declined between 18 and 25 years [odds ratio (OR) per year = 0.87, 95% confidence interval (CI) 0.79–0.95], and generalized anxiety disorder and major depressive episode became more common (OR 1.22, 95% CI 1.10–1.35 per year; OR 1.20, 95% CI 1.10–1.30 respectively).
ConclusionsThis contemporary EP/ELBW cohort has comparable young adult mental health outcomes to controls, and similar patterns of change in mental health from late adolescence.
Conducting Clinical Trials in Twin Populations: A Review of Design, Analysis, Recruitment and Ethical Issues for Twin-Only Trials
- Lisa N. Yelland, Katrina J. Scurrah, Paulo Ferreira, Lucas Calais-Ferreira, Monica Rankin, Jane Denton, Merryl Harvey, Katherine J. Lee, Evie Kendal, Jeffrey M. Craig
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- Twin Research and Human Genetics / Volume 24 / Issue 6 / December 2021
- Published online by Cambridge University Press:
- 25 January 2022, pp. 359-364
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Although twins often participate in medical research, few clinical trials are conducted entirely in twin populations. The purpose of this review is to demonstrate the substantial benefits and address the key challenges of conducting clinical trials in twin populations, or ‘twin-only trials’. We consider the unique design, analysis, recruitment and ethical issues that arise in such trials. In particular, we describe the different approaches available for randomizing twin pairs, highlight the similarity or correlation that exists between outcomes of twins, and discuss the impact of this correlation on sample size calculations and statistical analysis methods for estimating treatment effects. We also consider the role of both monozygotic and dizygotic twins for studying variation in outcomes, the factors that may affect recruitment of twins, and the ethics of conducting trials entirely in twin populations. The advantages and disadvantages of conducting twin-only trials are also discussed. Finally, we recommend that twin-only trials should be considered more often.
Pain Influences Neuropsychological Performance Following Electrical Injury: A Cross-Sectional Study
- Katherine E. Dorociak, Jason R. Soble, Patricia A. Rupert, Joseph W. Fink, Raphael C. Lee, Magdalena Anitescu, David Weiss, Gerald Cooke, Zachary J. Resch, Neil H. Pliskin
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- Journal of the International Neuropsychological Society / Volume 29 / Issue 1 / January 2023
- Published online by Cambridge University Press:
- 18 January 2022, pp. 35-45
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Objective:
Electrical injury (EI) is a significant, multifaceted trauma often with multi-domain cognitive sequelae, even when the expected current path does not pass through the brain. Chronic pain (CP) research suggests pain may affect cognition directly and indirectly by influencing emotional distress which then impacts cognitive functioning. As chronic pain may be critical to understanding EI-related cognitive difficulties, the aims of the current study were: examine the direct and indirect effects of pain on cognition following EI and compare the relationship between pain and cognition in EI and CP populations.
Method:This cross-sectional study used data from a clinical sample of 50 patients with EI (84.0% male; M age = 43.7 years) administered standardized measures of pain (Pain Patient Profile), depression, and neurocognitive functioning. A CP comparison sample of 93 patients was also included.
Results:Higher pain levels were associated with poorer attention/processing speed and executive functioning performance among patients with EI. Depression was significantly correlated with pain and mediated the relationship between pain and attention/processing speed in patients with EI. When comparing the patients with EI and CP, the relationship between pain and cognition was similar for both clinical groups.
Conclusions:Findings indicate that pain impacts mood and cognition in patients with EI, and the influence of pain and its effect on cognition should be considered in the assessment and treatment of patients who have experienced an electrical injury.
Brain glutathione levels and age at onset of illness in chronic schizophrenia
- Yvonne S. Yang, Richard J. Maddock, Junghee Lee, Huailin Zhang, Gerhard Hellemann, Katherine L. Narr, Stephen R. Marder, Michael F. Green
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- Acta Neuropsychiatrica / Volume 31 / Issue 6 / December 2019
- Published online by Cambridge University Press:
- 27 August 2019, pp. 343-347
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Objective:
Oxidative stress is implicated in the aetiology of schizophrenia, and the antioxidant defence system (AODS) may be protective in this illness. We examined the major antioxidant glutathione (GSH) in prefrontal brain and its correlates with clinical and demographic variables in schizophrenia.
Methods:GSH levels were measured in the dorsolateral prefrontal region of 28 patients with chronic schizophrenia using a magnetic resonance spectroscopy sequence specifically adapted for GSH. We examined correlations of GSH levels with age, age at onset of illness, duration of illness, and clinical symptoms.
Results:We found a negative correlation between GSH levels and age at onset (r = −0.46, p = 0.015), and a trend-level positive relationship between GSH and duration of illness (r = 0.34, p = 0.076).
Conclusion:Our findings are consistent with a possible compensatory upregulation of the AODS with longer duration of illness and suggest that the AODS may play a role in schizophrenia.
Neurodevelopmental Outcomes and Neural Mechanisms Associated with Non-right Handedness in Children Born Very Preterm
- Leona Pascoe, Shannon E. Scratch, Alice C. Burnett, Deanne K. Thompson, Katherine J. Lee, Lex W. Doyle, Jeanie L.Y. Cheong, Terrie E. Inder, Peter J. Anderson
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- Journal of the International Neuropsychological Society / Volume 21 / Issue 8 / September 2015
- Published online by Cambridge University Press:
- 02 September 2015, pp. 610-621
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Non-right handedness (NRH) is reportedly more common in very preterm (VPT; <32 weeks’ gestation) children compared with term-born peers, but it is unclear whether neonatal brain injury or altered brain morphology and microstructure underpins NRH in this population. Given that NRH has been inconsistently reported to be associated with cognitive and motor difficulties, this study aimed to examine associations between handedness and neurodevelopmental outcomes in VPT 7-year-olds. Furthermore, the relationship between neonatal brain injury and integrity of motor tracts (corpus callosum and corticospinal tract) with handedness at age 7 years in VPT children was explored. One hundred seventy-five VPT and 69 term-born children completed neuropsychological and motor assessments and a measure of handedness at 7 years’ corrected age. At term-equivalent age, brain injury on MRI was assessed and diffusion tensor measures were obtained for the corpus callosum and posterior limb of the internal capsule. There was little evidence of stronger NRH in the VPT group compared with term controls (regression coefficient [b] −1.95, 95% confidence interval [−5.67, 1.77]). Poorer academic and working memory outcomes were associated with stronger NRH in the VPT group. While there was little evidence that neonatal unilateral brain injury was associated with stronger NRH, increased area and fractional anisotropy of the corpus callosum splenium were predictive of stronger NRH in the VPT group. VPT birth may alter the relationship between handedness and academic outcomes, and neonatal corpus callosum integrity predicts hand preference in VPT children at school age. (JINS, 2015, 21, 610–621)
The Farm Level Effects of Better Access to Information: The Case of Dart
- Darrell J. Bosch, Katherine L. Lee
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- Journal of Agricultural and Applied Economics / Volume 20 / Issue 2 / December 1988
- Published online by Cambridge University Press:
- 28 April 2015, pp. 109-118
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In this study, two methods of entering and accessing dairy herd records are compared: the traditional mail-in Dairy Herd Improvement (DHI) system and the Direct Access to Records by Telephone (DART) system, which provides more timely and convenient access to records. An evaluation of DART was carried out using mail survey responses from 117 DART users and telephone surveys of 40 randomly selected users. Results indicate that DART users are generally satisfied with the system and feel that it improves their herd management. Variations in use of the DART system by DART users are explained by herd, cost, and management variables. DART users and comparable non-DART, DHI users are compared with respect to gains in herd production efficiency. Results indicate that DART users made somewhat better gains in most efficiency measures but that the differences were generally not statistically significant.
Contributors
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- By Mitchell Aboulafia, Frederick Adams, Marilyn McCord Adams, Robert M. Adams, Laird Addis, James W. Allard, David Allison, William P. Alston, Karl Ameriks, C. Anthony Anderson, David Leech Anderson, Lanier Anderson, Roger Ariew, David Armstrong, Denis G. Arnold, E. J. Ashworth, Margaret Atherton, Robin Attfield, Bruce Aune, Edward Wilson Averill, Jody Azzouni, Kent Bach, Andrew Bailey, Lynne Rudder Baker, Thomas R. Baldwin, Jon Barwise, George Bealer, William Bechtel, Lawrence C. Becker, Mark A. Bedau, Ernst Behler, José A. Benardete, Ermanno Bencivenga, Jan Berg, Michael Bergmann, Robert L. Bernasconi, Sven Bernecker, Bernard Berofsky, Rod Bertolet, Charles J. Beyer, Christian Beyer, Joseph Bien, Joseph Bien, Peg Birmingham, Ivan Boh, James Bohman, Daniel Bonevac, Laurence BonJour, William J. Bouwsma, Raymond D. Bradley, Myles Brand, Richard B. Brandt, Michael E. Bratman, Stephen E. Braude, Daniel Breazeale, Angela Breitenbach, Jason Bridges, David O. Brink, Gordon G. Brittan, Justin Broackes, Dan W. Brock, Aaron Bronfman, Jeffrey E. Brower, Bartosz Brozek, Anthony Brueckner, Jeffrey Bub, Lara Buchak, Otavio Bueno, Ann E. Bumpus, Robert W. Burch, John Burgess, Arthur W. Burks, Panayot Butchvarov, Robert E. Butts, Marina Bykova, Patrick Byrne, David Carr, Noël Carroll, Edward S. Casey, Victor Caston, Victor Caston, Albert Casullo, Robert L. Causey, Alan K. L. Chan, Ruth Chang, Deen K. Chatterjee, Andrew Chignell, Roderick M. Chisholm, Kelly J. Clark, E. J. Coffman, Robin Collins, Brian P. Copenhaver, John Corcoran, John Cottingham, Roger Crisp, Frederick J. Crosson, Antonio S. Cua, Phillip D. Cummins, Martin Curd, Adam Cureton, Andrew Cutrofello, Stephen Darwall, Paul Sheldon Davies, Wayne A. Davis, Timothy Joseph Day, Claudio de Almeida, Mario De Caro, Mario De Caro, John Deigh, C. F. Delaney, Daniel C. Dennett, Michael R. DePaul, Michael Detlefsen, Daniel Trent Devereux, Philip E. Devine, John M. Dillon, Martin C. Dillon, Robert DiSalle, Mary Domski, Alan Donagan, Paul Draper, Fred Dretske, Mircea Dumitru, Wilhelm Dupré, Gerald Dworkin, John Earman, Ellery Eells, Catherine Z. Elgin, Berent Enç, Ronald P. Endicott, Edward Erwin, John Etchemendy, C. Stephen Evans, Susan L. Feagin, Solomon Feferman, Richard Feldman, Arthur Fine, Maurice A. Finocchiaro, William FitzPatrick, Richard E. Flathman, Gvozden Flego, Richard Foley, Graeme Forbes, Rainer Forst, Malcolm R. Forster, Daniel Fouke, Patrick Francken, Samuel Freeman, Elizabeth Fricker, Miranda Fricker, Michael Friedman, Michael Fuerstein, Richard A. Fumerton, Alan Gabbey, Pieranna Garavaso, Daniel Garber, Jorge L. A. Garcia, Robert K. Garcia, Don Garrett, Philip Gasper, Gerald Gaus, Berys Gaut, Bernard Gert, Roger F. Gibson, Cody Gilmore, Carl Ginet, Alan H. Goldman, Alvin I. Goldman, Alfonso Gömez-Lobo, Lenn E. Goodman, Robert M. Gordon, Stefan Gosepath, Jorge J. E. Gracia, Daniel W. Graham, George A. Graham, Peter J. Graham, Richard E. Grandy, I. Grattan-Guinness, John Greco, Philip T. Grier, Nicholas Griffin, Nicholas Griffin, David A. Griffiths, Paul J. Griffiths, Stephen R. Grimm, Charles L. Griswold, Charles B. Guignon, Pete A. Y. Gunter, Dimitri Gutas, Gary Gutting, Paul Guyer, Kwame Gyekye, Oscar A. Haac, Raul Hakli, Raul Hakli, Michael Hallett, Edward C. Halper, Jean Hampton, R. James Hankinson, K. R. Hanley, Russell Hardin, Robert M. Harnish, William Harper, David Harrah, Kevin Hart, Ali Hasan, William Hasker, John Haugeland, Roger Hausheer, William Heald, Peter Heath, Richard Heck, John F. Heil, Vincent F. Hendricks, Stephen Hetherington, Francis Heylighen, Kathleen Marie Higgins, Risto Hilpinen, Harold T. Hodes, Joshua Hoffman, Alan Holland, Robert L. Holmes, Richard Holton, Brad W. Hooker, Terence E. Horgan, Tamara Horowitz, Paul Horwich, Vittorio Hösle, Paul Hoβfeld, Daniel Howard-Snyder, Frances Howard-Snyder, Anne Hudson, Deal W. Hudson, Carl A. Huffman, David L. Hull, Patricia Huntington, Thomas Hurka, Paul Hurley, Rosalind Hursthouse, Guillermo Hurtado, Ronald E. Hustwit, Sarah Hutton, Jonathan Jenkins Ichikawa, Harry A. Ide, David Ingram, Philip J. Ivanhoe, Alfred L. Ivry, Frank Jackson, Dale Jacquette, Joseph Jedwab, Richard Jeffrey, David Alan Johnson, Edward Johnson, Mark D. Jordan, Richard Joyce, Hwa Yol Jung, Robert Hillary Kane, Tomis Kapitan, Jacquelyn Ann K. Kegley, James A. Keller, Ralph Kennedy, Sergei Khoruzhii, Jaegwon Kim, Yersu Kim, Nathan L. King, Patricia Kitcher, Peter D. Klein, E. D. Klemke, Virginia Klenk, George L. Kline, Christian Klotz, Simo Knuuttila, Joseph J. Kockelmans, Konstantin Kolenda, Sebastian Tomasz Kołodziejczyk, Isaac Kramnick, Richard Kraut, Fred Kroon, Manfred Kuehn, Steven T. Kuhn, Henry E. Kyburg, John Lachs, Jennifer Lackey, Stephen E. Lahey, Andrea Lavazza, Thomas H. Leahey, Joo Heung Lee, Keith Lehrer, Dorothy Leland, Noah M. Lemos, Ernest LePore, Sarah-Jane Leslie, Isaac Levi, Andrew Levine, Alan E. Lewis, Daniel E. Little, Shu-hsien Liu, Shu-hsien Liu, Alan K. L. Chan, Brian Loar, Lawrence B. Lombard, John Longeway, Dominic McIver Lopes, Michael J. Loux, E. J. Lowe, Steven Luper, Eugene C. Luschei, William G. Lycan, David Lyons, David Macarthur, Danielle Macbeth, Scott MacDonald, Jacob L. Mackey, Louis H. Mackey, Penelope Mackie, Edward H. Madden, Penelope Maddy, G. B. Madison, Bernd Magnus, Pekka Mäkelä, Rudolf A. Makkreel, David Manley, William E. Mann (W.E.M.), Vladimir Marchenkov, Peter Markie, Jean-Pierre Marquis, Ausonio Marras, Mike W. Martin, A. P. Martinich, William L. McBride, David McCabe, Storrs McCall, Hugh J. McCann, Robert N. McCauley, John J. McDermott, Sarah McGrath, Ralph McInerny, Daniel J. McKaughan, Thomas McKay, Michael McKinsey, Brian P. McLaughlin, Ernan McMullin, Anthonie Meijers, Jack W. Meiland, William Jason Melanson, Alfred R. Mele, Joseph R. Mendola, Christopher Menzel, Michael J. Meyer, Christian B. Miller, David W. Miller, Peter Millican, Robert N. Minor, Phillip Mitsis, James A. Montmarquet, Michael S. Moore, Tim Moore, Benjamin Morison, Donald R. Morrison, Stephen J. Morse, Paul K. Moser, Alexander P. D. Mourelatos, Ian Mueller, James Bernard Murphy, Mark C. Murphy, Steven Nadler, Jan Narveson, Alan Nelson, Jerome Neu, Samuel Newlands, Kai Nielsen, Ilkka Niiniluoto, Carlos G. Noreña, Calvin G. Normore, David Fate Norton, Nikolaj Nottelmann, Donald Nute, David S. Oderberg, Steve Odin, Michael O’Rourke, Willard G. Oxtoby, Heinz Paetzold, George S. Pappas, Anthony J. Parel, Lydia Patton, R. P. Peerenboom, Francis Jeffry Pelletier, Adriaan T. Peperzak, Derk Pereboom, Jaroslav Peregrin, Glen Pettigrove, Philip Pettit, Edmund L. Pincoffs, Andrew Pinsent, Robert B. Pippin, Alvin Plantinga, Louis P. Pojman, Richard H. Popkin, John F. Post, Carl J. Posy, William J. Prior, Richard Purtill, Michael Quante, Philip L. Quinn, Philip L. Quinn, Elizabeth S. Radcliffe, Diana Raffman, Gerard Raulet, Stephen L. Read, Andrews Reath, Andrew Reisner, Nicholas Rescher, Henry S. Richardson, Robert C. Richardson, Thomas Ricketts, Wayne D. Riggs, Mark Roberts, Robert C. Roberts, Luke Robinson, Alexander Rosenberg, Gary Rosenkranz, Bernice Glatzer Rosenthal, Adina L. Roskies, William L. Rowe, T. M. Rudavsky, Michael Ruse, Bruce Russell, Lilly-Marlene Russow, Dan Ryder, R. M. Sainsbury, Joseph Salerno, Nathan Salmon, Wesley C. Salmon, Constantine Sandis, David H. Sanford, Marco Santambrogio, David Sapire, Ruth A. Saunders, Geoffrey Sayre-McCord, Charles Sayward, James P. Scanlan, Richard Schacht, Tamar Schapiro, Frederick F. Schmitt, Jerome B. Schneewind, Calvin O. Schrag, Alan D. Schrift, George F. Schumm, Jean-Loup Seban, David N. Sedley, Kenneth Seeskin, Krister Segerberg, Charlene Haddock Seigfried, Dennis M. Senchuk, James F. Sennett, William Lad Sessions, Stewart Shapiro, Tommie Shelby, Donald W. Sherburne, Christopher Shields, Roger A. Shiner, Sydney Shoemaker, Robert K. Shope, Kwong-loi Shun, Wilfried Sieg, A. John Simmons, Robert L. Simon, Marcus G. Singer, Georgette Sinkler, Walter Sinnott-Armstrong, Matti T. Sintonen, Lawrence Sklar, Brian Skyrms, Robert C. Sleigh, Michael Anthony Slote, Hans Sluga, Barry Smith, Michael Smith, Robin Smith, Robert Sokolowski, Robert C. Solomon, Marta Soniewicka, Philip Soper, Ernest Sosa, Nicholas Southwood, Paul Vincent Spade, T. L. S. Sprigge, Eric O. Springsted, George J. Stack, Rebecca Stangl, Jason Stanley, Florian Steinberger, Sören Stenlund, Christopher Stephens, James P. Sterba, Josef Stern, Matthias Steup, M. A. Stewart, Leopold Stubenberg, Edith Dudley Sulla, Frederick Suppe, Jere Paul Surber, David George Sussman, Sigrún Svavarsdóttir, Zeno G. Swijtink, Richard Swinburne, Charles C. Taliaferro, Robert B. Talisse, John Tasioulas, Paul Teller, Larry S. Temkin, Mark Textor, H. S. Thayer, Peter Thielke, Alan Thomas, Amie L. Thomasson, Katherine Thomson-Jones, Joshua C. Thurow, Vzalerie Tiberius, Terrence N. Tice, Paul Tidman, Mark C. Timmons, William Tolhurst, James E. Tomberlin, Rosemarie Tong, Lawrence Torcello, Kelly Trogdon, J. D. Trout, Robert E. Tully, Raimo Tuomela, John Turri, Martin M. Tweedale, Thomas Uebel, Jennifer Uleman, James Van Cleve, Harry van der Linden, Peter van Inwagen, Bryan W. Van Norden, René van Woudenberg, Donald Phillip Verene, Samantha Vice, Thomas Vinci, Donald Wayne Viney, Barbara Von Eckardt, Peter B. M. Vranas, Steven J. Wagner, William J. Wainwright, Paul E. Walker, Robert E. Wall, Craig Walton, Douglas Walton, Eric Watkins, Richard A. Watson, Michael V. Wedin, Rudolph H. Weingartner, Paul Weirich, Paul J. Weithman, Carl Wellman, Howard Wettstein, Samuel C. Wheeler, Stephen A. White, Jennifer Whiting, Edward R. Wierenga, Michael Williams, Fred Wilson, W. Kent Wilson, Kenneth P. Winkler, John F. Wippel, Jan Woleński, Allan B. Wolter, Nicholas P. Wolterstorff, Rega Wood, W. Jay Wood, Paul Woodruff, Alison Wylie, Gideon Yaffe, Takashi Yagisawa, Yutaka Yamamoto, Keith E. Yandell, Xiaomei Yang, Dean Zimmerman, Günter Zoller, Catherine Zuckert, Michael Zuckert, Jack A. Zupko (J.A.Z.)
- Edited by Robert Audi, University of Notre Dame, Indiana
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- Book:
- The Cambridge Dictionary of Philosophy
- Published online:
- 05 August 2015
- Print publication:
- 27 April 2015, pp ix-xxx
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- By Naila A. Ahmad, Dua M. Anderson, Jennifer Aunspaugh, Sabrina T. Bent, Adam Broussard, Staci Cameron, Rahul Dasgupta, Ravinder Devgun, Ofer N. Eytan, Sean H. Flack, Terry G. Fletcher, Charles James Fox, Mary Elise Fox, Scott Friedman, Louise K. Furukawa, Sonja Gennuso, Stanley M. Hall, Hani Hanna, Jacob Hummel, James E. Hunt, Ranu Jain, Joe R. Jansen, Deepa Kattail, Alan David Kaye, David J. Krodel, Gregory J. Latham, Sungeun Lee, Michael G. Levitzky, Alexander Y. Lin, Carl Lo, Hoa N. Luu, Camila Lyon, Kelly A. Machovec, Lizabeth D. Martin, Maria Matuszczak, Patrick S. McCarty, Brenda C. McClain, J. Grant McFadyen, Helen Nazareth, Dolores B. Njoku, Christina M. Pabelick, Shannon M. Peters, Amit Prabhakar, Michael Richards, Kasia Rubin, Joel A. Saltzman, Lisgelia Santana, Gabriel Sarah, Katherine Stammen, John Stork, Kim M. Strupp, Lalitha V. Sundararaman, Rosalie F. Tassone, Douglas R. Thompson, Nicole C. P. Thompson, Paul A. Tripi, Jacqueline L. Tutiven, Navyugjit Virk, Stacey Watt, B. Craig Weldon, Maria Zestus
- Edited by Alan David Kaye, Louisiana State University, Charles James Fox, Tulane University School of Medicine, Louisiana, James H. Diaz, Louisiana State University
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- Essentials of Pediatric Anesthesiology
- Published online:
- 05 November 2014
- Print publication:
- 16 October 2014, pp ix-xii
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Hippocampal Volume and Memory and Learning Outcomes at 7 Years in Children Born Very Preterm
- Cristina Omizzolo, Deanne K. Thompson, Shannon E. Scratch, Robyn Stargatt, Katherine J. Lee, Jeanie Cheong, Gehan Roberts, Lex W. Doyle, Peter J. Anderson
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- Journal:
- Journal of the International Neuropsychological Society / Volume 19 / Issue 10 / November 2013
- Published online by Cambridge University Press:
- 15 August 2013, pp. 1065-1075
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Using magnetic resonance imaging, this study compared hippocampal volume between 145 very preterm children and 34 children born full-term at 7 years of age. The relationship between hippocampal volume and memory and learning impairments at 7 years was also investigated. Manual hippocampal segmentation and subsequent three-dimensional volumetric analysis revealed reduced hippocampal volumes in very preterm children compared with term peers. However, this relationship did not remain after correcting for whole brain volume and neonatal brain abnormality. Contrary to expectations, hippocampal volume in the very preterm cohort was not related to memory and learning outcomes. Further research investigating the effects of very preterm birth on more extensive networks in the brain that support memory and learning in middle childhood is needed. (JINS, 2013, 19, 1–11)
Contributors
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- By Robert C. Basner, Carl Bazil, Lee J. Brooks, Sean M. Caples, Kelly A. Carden, Ronald D. Chervin, Christopher Cielo, David G. Davila, Katherine A. Dudley, Judy Fetterolf, W. Ward Flemons, Neil Freedman, Christian Guilleminault, Fauziya Hassan, Shelley Hershner, David M. Hiestand, Mithri Junna, Kristen Kelly-Pieper, Douglas Kirsch, Brian B. Koo, Carin Lamm, Raman Malhotra, Meghna P. Mansukhani, Carole L. Marcus, B. Marshall, Jean K. Matheson, Timothy I. Morgenthaler, Gökhan M. Mutlu, Irina Ok, Vidya Pai, Winnie C. Pao, Sairam Parthasarathy, Shalini Paruthi, Nimesh Patel, Sachin R. Pendharkar, Ravi K. Persaud, Bharati Prasad, Stuart F. Quan, Satish C. Rao, Patti Reed, Alcibiades Rodriguez, Dennis Rosen, Vijay Seelall, Anita Valanju Shelgikar, Jeffrey J. Stanley, Kingman Strohl, Shannon S. Sullivan, Kevin A. Thomas, Robert Thomas, John R. Wheatley, Lisa Wolfe, Peter J.-C. Wu, Motoo Yamauchi
- Edited by Robert C. Basner
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- Case Studies in Polysomnography Interpretation
- Published online:
- 05 August 2015
- Print publication:
- 18 October 2012, pp x-xii
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- By Kumar Alagappan, Janet G. Alteveer, Kim Askew, Paul S. Auerbach, Katherine Bakes, Kip Benko, Paul D. Biddinger, Victoria Brazil, Anthony FT Brown, Andrew K. Chang, Alice Chiao, Wendy C. Coates, Jamie Collings, Gilbert Abou Dagher, Jonathan E. Davis, Peter DeBlieux, Alessandro Dellai, Emily Doelger, Pamela L. Dyne, Gino Farina, Robert Galli, Gus M. Garmel, Daniel Garza, Laleh Gharahbaghian, Gregory H. Gilbert, Michael A. Gisondi, Steven Go, Jeffrey M. Goodloe, Swaminatha V. Gurudevan, Micelle J. Haydel, Stephen R. Hayden, Corey R. Heitz, Gregory W. Hendey, Mel Herbert, Cherri Hobgood, Michelle Huston, Loretta Jackson-Williams, Anja K. Jaehne, Mary Beth Johnson, H. Brendan Kelleher, Peter G Kumasaka, Melissa J. Lamberson, Mary Lanctot-Herbert, Erik Laurin, Brian Lin, Michelle Lin, Douglas Lowery-North, Sharon E. Mace, S. V. Mahadevan, Thomas M. Mailhot, Diku Mandavia, David E. Manthey, Jorge A. Martinez, Amal Mattu, Lynne McCullough, Steve McLaughlin, Timothy Meyers, Gregory J. Moran, Randall T. Myers, Christopher R.H. Newton, Flavia Nobay, Robert L. Norris, Catherine Oliver, Jennifer A. Oman, Rita Oregon, Phillips Perera, Susan B. Promes, Emanuel P. Rivers, John S. Rose, Carolyn J. Sachs, Jairo I. Santanilla, Rawle A. Seupaul, Fred A. Severyn, Ghazala Q. Sharieff, Lee W. Shockley, Stefanie Simmons, Barry C. Simon, Shannon Sovndal, George Sternbach, Matthew Strehlow, Eustacia (Jo) Su, Stuart P. Swadron, Jeffrey A. Tabas, Sophie Terp, R. Jason Thurman, David A. Wald, Sarah R. Williams, Teresa S. Wu, Ken Zafren
- Edited by S. V. Mahadevan, Stanford University School of Medicine, California, Gus M. Garmel
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- Book:
- An Introduction to Clinical Emergency Medicine
- Published online:
- 05 May 2012
- Print publication:
- 10 April 2012, pp xi-xvi
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Pump Wavelength Tuning of Optical Pumping Injection Cavity Lasers for Enhancing Mid-Infrared Operation
- Todd C. McAlpine, Katherine R. Greene, Michael R. Santilli, Linda J. Olafsen, William W. Bewley, Christopher L. Felix, Igor Vurgaftman, Jerry R. Meyer, M. J. Yang, Hao Lee, Ramon U. Martinelli
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- Journal:
- MRS Online Proceedings Library Archive / Volume 799 / 2003
- Published online by Cambridge University Press:
- 01 February 2011, Z4.7
- Print publication:
- 2003
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Recent efforts to improve the performance of mid-infrared antimonide-based semiconductor lasers have focused on enhancing the absorption of the pump beam to maximize power conversion efficiencies and minimize threshold intensities. One successful approach has been the optical pumping injection cavity (OPIC) laser, in which a type-II W active region is enclosed between distributed Bragg reflector (DBR) mirrors in order to achieve multiple passes of the pump beam and thereby to enhance absorption.
Previously, fixed wavelength sources have been used for optical pumping of OPIC laser structures, with limited tuning available by adjusting the incident angle. By tuning the pump wavelength using an optical parametric oscillator, we demonstrate minimum threshold intensities and maximum slope efficiencies at the resonance of the DBR cavity surrounding the active region, further demonstrating the potential of OPIC lasers. A 3.2 μm OPIC laser operated at 350 K in pulsed mode (at the highest operating temperature of the dewar), with a characteristic temperature of 50 K. The power conversion efficiency for a single facet at 300 K was the highest ever observed in the mid-IR, at approximately 4%.
Results are presented for two OPIC samples (emitting at ∼3.2 μm and 4.3 μm at high temperature), one of which was designed with a broadened cavity resonance, suitable for pumping with a multi-mode source. Threshold intensities and slope efficiencies measured as a function of pump wavelength demonstrate the strong resonance effect, and that the “broadened OPIC” does in fact manifest a much wider resonance than the non-broadened resonance cavity design.