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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.
Advocacy at the Eighth World Congress of Pediatric Cardiology and Cardiac Surgery
- Bistra Zheleva, Amy Verstappen, David M. Overman, Farhan Ahmad, Sulafa K.M. Ali, Zohair Y. Al Halees, Joumana Ghandour Atallah, Isabella E. Badhwar, Carissa Baker-Smith, Maria Balestrini, Amy Basken, Jonah S. Bassuk, Lee Benson, Horacio Capelli, Santo Carollo, Devyani Chowdhury, M. Sertaç Çiçek, Mitchell I. Cohen, David S. Cooper, John E. Deanfield, Joseph Dearani, Blanca del Valle, Kathryn M. Dodds, Junbao Du, Frank Edwin, Ekanem Ekure, Nurun Nahar Fatema, Anu Gomanju, Babar Hasan, Lewis Henry, Christopher Hugo-Hamman, Krishna S. Iyer, Marcelo B. Jatene, Kathy J. Jenkins, Tara Karamlou, Tom R. Karl, James K. Kirklin, Christián Kreutzer, Raman Krishna Kumar, Keila N. Lopez, Alexis Palacios Macedo, Bradley S. Marino, Eva M. Marwali, Folkert J. Meijboom, Sandra S. Mattos, Hani Najm, Dan Newlin, William M. Novick, Sir Shakeel A. Qureshi, Budi Rahmat, Robert Raylman, Irfan Levent Saltik, Craig Sable, Nestor Sandoval, Anita Saxena, Emma Scanlan, Gary F. Sholler, Jodi Smith, James D. St Louis, Christo I. Tchervenkov, Koh Ghee Tiong, Vladimiro Vida, Susan Vosloo, Douglas J. “DJ” Weinstein, James L. Wilkinson, Liesl Zuhlke, Jeffrey P. Jacobs
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- Journal:
- Cardiology in the Young / Volume 33 / Issue 8 / August 2023
- Published online by Cambridge University Press:
- 24 August 2023, pp. 1277-1287
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The Eighth World Congress of Pediatric Cardiology and Cardiac Surgery (WCPCCS) will be held in Washington DC, USA, from Saturday, 26 August, 2023 to Friday, 1 September, 2023, inclusive. The Eighth World Congress of Pediatric Cardiology and Cardiac Surgery will be the largest and most comprehensive scientific meeting dedicated to paediatric and congenital cardiac care ever held. At the time of the writing of this manuscript, The Eighth World Congress of Pediatric Cardiology and Cardiac Surgery has 5,037 registered attendees (and rising) from 117 countries, a truly diverse and international faculty of over 925 individuals from 89 countries, over 2,000 individual abstracts and poster presenters from 101 countries, and a Best Abstract Competition featuring 153 oral abstracts from 34 countries. For information about the Eighth World Congress of Pediatric Cardiology and Cardiac Surgery, please visit the following website: [www.WCPCCS2023.org]. The purpose of this manuscript is to review the activities related to global health and advocacy that will occur at the Eighth World Congress of Pediatric Cardiology and Cardiac Surgery.
Acknowledging the need for urgent change, we wanted to take the opportunity to bring a common voice to the global community and issue the Washington DC WCPCCS Call to Action on Addressing the Global Burden of Pediatric and Congenital Heart Diseases. A copy of this Washington DC WCPCCS Call to Action is provided in the Appendix of this manuscript. This Washington DC WCPCCS Call to Action is an initiative aimed at increasing awareness of the global burden, promoting the development of sustainable care systems, and improving access to high quality and equitable healthcare for children with heart disease as well as adults with congenital heart disease worldwide.
VERTICO V: The environmentally driven evolution of the inner cold gas discs of Virgo cluster galaxies
- Adam B. Watts, Luca Cortese, Barbara Catinella, Toby Brown, Christine D. Wilson, Nikki Zabel, Ian D. Roberts, Timothy A. Davis, Mallory Thorp, Aeree Chung, Adam R.H. Stevens, Sara L. Ellison, Kristine Spekkens, Laura C. Parker, Yannick M. Bahé, Vicente Villanueva, María Jiménez-Donaire, Dhruv Bisaria, Alessandro Boselli, Alberto D. Bolatto, Bumhyun Lee
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- Journal:
- Publications of the Astronomical Society of Australia / Volume 40 / 2023
- Published online by Cambridge University Press:
- 27 April 2023, e017
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The quenching of cluster satellite galaxies is inextricably linked to the suppression of their cold interstellar medium (ISM) by environmental mechanisms. While the removal of neutral atomic hydrogen (H i) at large radii is well studied, how the environment impacts the remaining gas in the centres of galaxies, which are dominated by molecular gas, is less clear. Using new observations from the Virgo Environment traced in CO survey (VERTICO) and archival H i data, we study the H i and molecular gas within the optical discs of Virgo cluster galaxies on 1.2-kpc scales with spatially resolved scaling relations between stellar ($\Sigma_{\star}$), H i ($\Sigma_{\text{H}\,{\small\text{I}}}$), and molecular gas ($\Sigma_{\text{mol}}$) surface densities. Adopting H i deficiency as a measure of environmental impact, we find evidence that, in addition to removing the H i at large radii, the cluster processes also lower the average $\Sigma_{\text{H}\,{\small\text{I}}}$ of the remaining gas even in the central $1.2\,$kpc. The impact on molecular gas is comparatively weaker than on the H i, and we show that the lower $\Sigma_{\text{mol}}$ gas is removed first. In the most H i-deficient galaxies, however, we find evidence that environmental processes reduce the typical $\Sigma_{\text{mol}}$ of the remaining gas by nearly a factor of 3. We find no evidence for environment-driven elevation of $\Sigma_{\text{H}\,{\small\text{I}}}$ or $\Sigma_{\text{mol}}$ in H i-deficient galaxies. Using the ratio of $\Sigma_{\text{mol}}$-to-$\Sigma_{\text{H}\,{\small\text{I}}}$ in individual regions, we show that changes in the ISM physical conditions, estimated using the total gas surface density and midplane hydrostatic pressure, cannot explain the observed reduction in molecular gas content. Instead, we suggest that direct stripping of the molecular gas is required to explain our results.
Educational initiative in an NCATS TL1 training program to address the impact of systemic racism on human health, biomedical research, and the translational scientist
- Martha D. Gay, Kimberly A. Bell, Emily A. Bujold, Marilla Geraci, Dexter L. Lee, Kathryn Sandberg, Robert C. Speth
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- Journal:
- Journal of Clinical and Translational Science / Volume 6 / Issue 1 / 2022
- Published online by Cambridge University Press:
- 14 November 2022, e145
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Introduction:
The goal of clinical and translational science (CTS) is to fill gaps in medical knowledge toward improving human health. However, one of our most pressing challenges does not reside within the biological map we navigate to find sustainable cures but rather the moral compass to recognize and overcome racial and ethnic injustices that continue to influence our society and hinder diverse research rigor. The Georgetown-Howard Universities Center for Clinical and Translational Science includes an inter-institutional TL1-funded training program for predoctoral/postdoctoral trainees in Translational Biomedical Science (TBS).
Methods:In the fall of 2020, the TBS program responded to the national social justice crisis by incorporating a curriculum focused on structural racism in biomedical research. Educational platforms, including movie reviews, Journal Clubs, and other workshops, were threaded throughout the curriculum by ensuring safe spaces to discuss racial and ethnic injustices and providing trainees with practical steps to recognize, approach, and respond to these harmful biases in the CTS. Workshops also focused on why individuals underrepresented in science are vital for addressing and closing gaps in CTS.
Results:Paring analysis using REDCap software de-identified participants after invitations were sent and collected in the system to maintain anonymity for pre- and post-analysis. The Likert scale evaluated respondents’ understanding of diverse scientific circumstances. The pre/Fall and post/Spring surveys suggested this curriculum was successful at raising institutional awareness of racial and ethnic biases. Evaluating the effectiveness of our program with other training Clinical and Translational Science Awards (CTSA) consortiums will strengthen both the academic and professional TBS programs.
Derivation and validation of risk prediction for posttraumatic stress symptoms following trauma exposure
- Raphael Kim, Tina Lin, Gehao Pang, Yufeng Liu, Andrew S. Tungate, Phyllis L. Hendry, Michael C. Kurz, David A. Peak, Jeffrey Jones, Niels K. Rathlev, Robert A. Swor, Robert Domeier, Marc-Anthony Velilla, Christopher Lewandowski, Elizabeth Datner, Claire Pearson, David Lee, Patricia M. Mitchell, Samuel A. McLean, Sarah D. Linnstaedt
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- Psychological Medicine / Volume 53 / Issue 11 / August 2023
- Published online by Cambridge University Press:
- 01 July 2022, pp. 4952-4961
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Background
Posttraumatic stress symptoms (PTSS) are common following traumatic stress exposure (TSE). Identification of individuals with PTSS risk in the early aftermath of TSE is important to enable targeted administration of preventive interventions. In this study, we used baseline survey data from two prospective cohort studies to identify the most influential predictors of substantial PTSS.
MethodsSelf-identifying black and white American women and men (n = 1546) presenting to one of 16 emergency departments (EDs) within 24 h of motor vehicle collision (MVC) TSE were enrolled. Individuals with substantial PTSS (⩾33, Impact of Events Scale – Revised) 6 months after MVC were identified via follow-up questionnaire. Sociodemographic, pain, general health, event, and psychological/cognitive characteristics were collected in the ED and used in prediction modeling. Ensemble learning methods and Monte Carlo cross-validation were used for feature selection and to determine prediction accuracy. External validation was performed on a hold-out sample (30% of total sample).
ResultsTwenty-five percent (n = 394) of individuals reported PTSS 6 months following MVC. Regularized linear regression was the top performing learning method. The top 30 factors together showed good reliability in predicting PTSS in the external sample (Area under the curve = 0.79 ± 0.002). Top predictors included acute pain severity, recovery expectations, socioeconomic status, self-reported race, and psychological symptoms.
ConclusionsThese analyses add to a growing literature indicating that influential predictors of PTSS can be identified and risk for future PTSS estimated from characteristics easily available/assessable at the time of ED presentation following TSE.
The characteristics of patients requiring readmission to an Australian forensic psychiatric intensive care unit
- T. Jones, E. Harris, M. Roberts, D. Mawren, S. Lee
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- European Psychiatry / Volume 64 / Issue S1 / April 2021
- Published online by Cambridge University Press:
- 13 August 2021, p. S377
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Introduction
Psychiatric intensive care units (or PICU’s) emerged to manage high acuity patients outside the justice system. Studies have sought to better understand characteristics of those admitted to forensic or civilian PICU’s. Few, in contrast, have explored the frequency and contributors to readmission. The following study was conducted on Apsley unit, a Forensic PICU based in Melbourne, Australia, and seeks to understand the differences which would allow early identification of patients likely to require readmission and the provision of targeted interventions.
ObjectivesExamine rates of and contributors to forensic PICU readmission over a 6-month period.
MethodsA retrospective audit was conducted to collect clinical, problem behaviour (and strategies to manage), forensic history and demographic information for consecutively admitted patients to an 8-bed forensic PICU between March-September 2019.
ResultsData analysis is ongoing. Interim analysis found that 96 patients were admitted during the 6-month study period: 74 (77.1%) had a single admission; 22 (22.9%) required readmission. Almost all were admitted from prison (96.9%), most had a psychosis diagnosis (80.2%) and substance abuse history (96.9%), and many had a personality disorder (24.0%) and history of adolescent antisocial behaviour (46.5%). Patients requiring readmission were significantly more likely to have been previously under compulsory mental health treatment (95.5% vs 75.3%, p=.039) and have a Positive Behaviour Support Plan developed during admission (85.7% vs 54.8%, p=.010).
ConclusionsInterim analysis highlighted the multicomplexity for forensic PICU patients alongside the occurrence of problem behaviour during admission and history of compulsory treatment as indicators of increased risk for re-admission.
Prenatal maternal transdiagnostic, RDoC-informed predictors of newborn neurobehavior: Differences by sex
- Mengyu (Miranda) Gao, Brendan Ostlund, Mindy A. Brown, Parisa R. Kaliush, Sarah Terrell, Robert D. Vlisides-Henry, K. Lee Raby, Sheila E. Crowell, Elisabeth Conradt
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- Journal:
- Development and Psychopathology / Volume 33 / Issue 5 / December 2021
- Published online by Cambridge University Press:
- 29 March 2021, pp. 1554-1565
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We examined whether Research Domain Criteria (RDoC)-informed measures of prenatal stress predicted newborn neurobehavior and whether these effects differed by newborn sex. Multilevel, prenatal markers of prenatal stress were obtained from 162 pregnant women. Markers of the Negative Valence System included physiological functioning (respiratory sinus arrhythmia [RSA] and electrodermal [EDA] reactivity to a speech task, hair cortisol), self-reported stress (state anxiety, pregnancy-specific anxiety, daily stress, childhood trauma, economic hardship, and family resources), and interviewer-rated stress (episodic stress, chronic stress). Markers of the Arousal/Regulatory System included physiological functioning (baseline RSA, RSA, and EDA responses to infant cries) and self-reported affect intensity, urgency, emotion regulation strategies, and dispositional mindfulness. Newborns’ arousal and attention were assessed via the Neonatal Intensive Care Unit (NICU) Network Neurobehavioral Scale. Path analyses showed that high maternal episodic and daily stress, low economic hardship, few emotion regulation strategies, and high baseline RSA predicted female newborns’ low attention; maternal mindfulness predicted female newborns’ high arousal. As for male newborns, high episodic stress predicted low arousal, and high pregnancy-specific anxiety predicted high attention. Findings suggest that RDoC-informed markers of prenatal stress could aid detection of variance in newborn neurobehavioral outcomes within hours after birth. Implications for intergenerational transmission of risk for psychopathology are discussed.
Australian square kilometre array pathfinder: I. system description
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- A. W. Hotan, J. D. Bunton, A. P. Chippendale, M. Whiting, J. Tuthill, V. A. Moss, D. McConnell, S. W. Amy, M. T. Huynh, J. R. Allison, C. S. Anderson, K. W. Bannister, E. Bastholm, R. Beresford, D. C.-J. Bock, R. Bolton, J. M. Chapman, K. Chow, J. D. Collier, F. R. Cooray, T. J. Cornwell, P. J. Diamond, P. G. Edwards, I. J. Feain, T. M. O. Franzen, D. George, N. Gupta, G. A. Hampson, L. Harvey-Smith, D. B. Hayman, I. Heywood, C. Jacka, C. A. Jackson, S. Jackson, K. Jeganathan, S. Johnston, M. Kesteven, D. Kleiner, B. S. Koribalski, K. Lee-Waddell, E. Lenc, E. S. Lensson, S. Mackay, E. K. Mahony, N. M. McClure-Griffiths, R. McConigley, P. Mirtschin, A. K. Ng, R. P. Norris, S. E. Pearce, C. Phillips, M. A. Pilawa, W. Raja, J. E. Reynolds, P. Roberts, D. N. Roxby, E. M. Sadler, M. Shields, A. E. T. Schinckel, P. Serra, R. D. Shaw, T. Sweetnam, E. R. Troup, A. Tzioumis, M. A. Voronkov, T. Westmeier
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- Publications of the Astronomical Society of Australia / Volume 38 / 2021
- Published online by Cambridge University Press:
- 05 March 2021, e009
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In this paper, we describe the system design and capabilities of the Australian Square Kilometre Array Pathfinder (ASKAP) radio telescope at the conclusion of its construction project and commencement of science operations. ASKAP is one of the first radio telescopes to deploy phased array feed (PAF) technology on a large scale, giving it an instantaneous field of view that covers $31\,\textrm{deg}^{2}$ at $800\,\textrm{MHz}$. As a two-dimensional array of 36$\times$12 m antennas, with baselines ranging from 22 m to 6 km, ASKAP also has excellent snapshot imaging capability and 10 arcsec resolution. This, combined with 288 MHz of instantaneous bandwidth and a unique third axis of rotation on each antenna, gives ASKAP the capability to create high dynamic range images of large sky areas very quickly. It is an excellent telescope for surveys between 700 and $1800\,\textrm{MHz}$ and is expected to facilitate great advances in our understanding of galaxy formation, cosmology, and radio transients while opening new parameter space for discovery of the unknown.
Socio-demographic and trauma-related predictors of depression within eight weeks of motor vehicle collision in the AURORA study
- Jutta Joormann, Samuel A. McLean, Francesca L. Beaudoin, Xinming An, Jennifer S. Stevens, Donglin Zeng, Thomas C. Neylan, Gari Clifford, Sarah D. Linnstaedt, Laura T. Germine, Scott L. Rauch, Paul I. Musey, Phyllis L. Hendry, Sophia Sheikh, Christopher W. Jones, Brittany E. Punches, Gregory Fermann, Lauren A. Hudak, Kamran Mohiuddin, Vishnu Murty, Meghan E. McGrath, John P. Haran, Jose Pascual, Mark Seamon, David A. Peak, Claire Pearson, Robert M. Domeier, Paulina Sergot, Roland Merchant, Leon D. Sanchez, Niels K. Rathlev, William F. Peacock, Steven E. Bruce, Deanna Barch, Diego A. Pizzagalli, Beatriz Luna, Steven E. Harte, Irving Hwang, Sue Lee, Nancy Sampson, Karestan C. Koenen, Kerry J. Ressler, Ronald C. Kessler
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- Journal:
- Psychological Medicine / Volume 52 / Issue 10 / July 2022
- Published online by Cambridge University Press:
- 29 October 2020, pp. 1934-1947
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Background
This is the first report on the association between trauma exposure and depression from the Advancing Understanding of RecOvery afteR traumA(AURORA) multisite longitudinal study of adverse post-traumatic neuropsychiatric sequelae (APNS) among participants seeking emergency department (ED) treatment in the aftermath of a traumatic life experience.
MethodsWe focus on participants presenting at EDs after a motor vehicle collision (MVC), which characterizes most AURORA participants, and examine associations of participant socio-demographics and MVC characteristics with 8-week depression as mediated through peritraumatic symptoms and 2-week depression.
ResultsEight-week depression prevalence was relatively high (27.8%) and associated with several MVC characteristics (being passenger v. driver; injuries to other people). Peritraumatic distress was associated with 2-week but not 8-week depression. Most of these associations held when controlling for peritraumatic symptoms and, to a lesser degree, depressive symptoms at 2-weeks post-trauma.
ConclusionsThese observations, coupled with substantial variation in the relative strength of the mediating pathways across predictors, raises the possibility of diverse and potentially complex underlying biological and psychological processes that remain to be elucidated in more in-depth analyses of the rich and evolving AURORA database to find new targets for intervention and new tools for risk-based stratification following trauma exposure.
Decreased Hospitalizations and Costs From Infection in Sixteen Nursing Homes in the SHIELD OC Regional Decolonization Initiative
- Gabrielle M. Gussin, James A. McKinnell, Raveena D. Singh, Ken Kleinman, Amherst Loren Miller, Raheeb Saavedra, Lauren Heim, Marlene Estevez, Tabitha D. Catuna, Eunjung Lee, Thomas Tjoa, Rachel Slayton, Nimalie Stone, John Jernigan, Matthew Zahn, Lynn Janssen, Shruti K Gohil, Philip Alan Robinson, Steven Park, Robert Weinstein, Mary Hayden, Cassiana E. Bittencourt, Ellena M. Peterson, Susan Huang
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- Journal:
- Infection Control & Hospital Epidemiology / Volume 41 / Issue S1 / October 2020
- Published online by Cambridge University Press:
- 02 November 2020, pp. s7-s8
- Print publication:
- October 2020
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Distinguished Oral
Background: Shared Healthcare Intervention to Eliminate Life-threatening Dissemination of MDROs in Orange County, California (SHIELD OC) was a CDC-funded regional decolonization intervention from April 2017 through July 2019 involving 38 hospitals, nursing homes (NHs), and long-term acute-care hospitals (LTACHs) to reduce MDROs. Decolonization in NH and LTACHs consisted of universal antiseptic bathing with chlorhexidine (CHG) for routine bathing and showering plus nasal iodophor decolonization (Monday through Friday, twice daily every other week). Hospitals used universal CHG in ICUs and provided daily CHG and nasal iodophor to patients in contact precautions. We sought to evaluate whether decolonization reduced hospitalization and associated healthcare costs due to infections among residents of NHs participating in SHIELD compared to nonparticipating NHs. Methods: Medicaid insurer data covering NH residents in Orange County were used to calculate hospitalization rates due to a primary diagnosis of infection (counts per member quarter), hospital bed days/member-quarter, and expenditures/member quarter from the fourth quarter of 2015 to the second quarter of 2019. We used a time-series design and a segmented regression analysis to evaluate changes attributable to the SHIELD OC intervention among participating and nonparticipating NHs. Results: Across the SHIELD OC intervention period, intervention NHs experienced a 44% decrease in hospitalization rates, a 43% decrease in hospital bed days, and a 53% decrease in Medicaid expenditures when comparing the last quarter of the intervention to the baseline period (Fig. 1). These data translated to a significant downward slope, with a reduction of 4% per quarter in hospital admissions due to infection (P < .001), a reduction of 7% per quarter in hospitalization days due to infection (P < .001), and a reduction of 9% per quarter in Medicaid expenditures (P = .019) per NH resident. Conclusions: The universal CHG bathing and nasal decolonization intervention adopted by NHs in the SHIELD OC collaborative resulted in large, meaningful reductions in hospitalization events, hospitalization days, and healthcare expenditures among Medicaid-insured NH residents. The findings led CalOptima, the Medicaid provider in Orange County, California, to launch an NH incentive program that provides dedicated training and covers the cost of CHG and nasal iodophor for OC NHs that enroll.
Funding: None
Disclosures: Gabrielle M. Gussin, University of California, Irvine, Stryker (Sage Products): Conducting studies in which contributed antiseptic product is provided to participating hospitals and nursing homes. Clorox: Conducting studies in which contributed antiseptic product is provided to participating hospitals and nursing homes. Medline: Conducting studies in which contributed antiseptic product is provided to participating hospitals and nursing homes. Xttrium: Conducting studies in which contributed antiseptic product is provided to participating hospitals and nursing homes.
Methods for training collaborative biostatisticians
- Gina-Maria Pomann, L. Ebony Boulware, Shari Messinger Cayetano, Manisha Desai, Felicity T. Enders, John A. Gallis, Jonathan Gelfond, Steven C. Grambow, Alexandra L. Hanlon, Angelean Hendrix, Pandurang Kulkarni, Jodi Lapidus, Hui-Jie Lee, Jonathan D. Mahnken, Julie P. McKeel, Rebecca Moen, Robert A. Oster, Sarah Peskoe, Greg Samsa, Thomas G. Stewart, Tracy Truong, Lisa Wruck, Samantha M. Thomas
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- Journal:
- Journal of Clinical and Translational Science / Volume 5 / Issue 1 / 2021
- Published online by Cambridge University Press:
- 04 August 2020, e26
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The emphasis on team science in clinical and translational research increases the importance of collaborative biostatisticians (CBs) in healthcare. Adequate training and development of CBs ensure appropriate conduct of robust and meaningful research and, therefore, should be considered as a high-priority focus for biostatistics groups. Comprehensive training enhances clinical and translational research by facilitating more productive and efficient collaborations. While many graduate programs in Biostatistics and Epidemiology include training in research collaboration, it is often limited in scope and duration. Therefore, additional training is often required once a CB is hired into a full-time position. This article presents a comprehensive CB training strategy that can be adapted to any collaborative biostatistics group. This strategy follows a roadmap of the biostatistics collaboration process, which is also presented. A TIE approach (Teach the necessary skills, monitor the Implementation of these skills, and Evaluate the proficiency of these skills) was developed to support the adoption of key principles. The training strategy also incorporates a “train the trainer” approach to enable CBs who have successfully completed training to train new staff or faculty.
Intergenerational transmission of emotion dysregulation: Part II. Developmental origins of newborn neurobehavior
- Brendan D. Ostlund, Robert D. Vlisides-Henry, Sheila E. Crowell, K. Lee Raby, Sarah Terrell, Mindy A. Brown, Ruben Tinajero, Nila Shakiba, Catherine Monk, Julie H. Shakib, Karen F. Buchi, Elisabeth Conradt
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- Journal:
- Development and Psychopathology / Volume 31 / Issue 3 / August 2019
- Published online by Cambridge University Press:
- 06 May 2019, pp. 833-846
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We investigated whether neurobehavioral markers of risk for emotion dysregulation were evident among newborns, as well as whether the identified markers were associated with prenatal exposure to maternal emotion dysregulation. Pregnant women (N = 162) reported on their emotion dysregulation prior to a laboratory assessment. The women were then invited to the laboratory to assess baseline respiratory sinus arrhythmia (RSA) and RSA in response to an infant cry. Newborns were assessed after birth via the NICU Network Neurobehavioral Scale. We identified two newborn neurobehavioral factors—arousal and attention—via exploratory factor analysis. Low arousal was characterized by less irritability, excitability, and motor agitation, while low attention was related to a lower threshold for auditory and visual stimulation, less sustained attention, and poorer visual tracking abilities. Pregnant women who reported higher levels of emotion dysregulation had newborns with low arousal levels and less attention. Larger decreases in maternal RSA in response to cry were also related to lower newborn arousal. We provide the first evidence that a woman's emotion dysregulation while pregnant is associated with risks for dysregulation in her newborn. Implications for intergenerational transmission of emotion dysregulation are discussed.
Spectral analysis of the budget equation in turbulent channel flows at high Reynolds number
- Myoungkyu Lee, Robert D. Moser
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- Journal:
- Journal of Fluid Mechanics / Volume 860 / 10 February 2019
- Published online by Cambridge University Press:
- 14 December 2018, pp. 886-938
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The transport equations for the variances of the velocity components are investigated using data from direct numerical simulations of incompressible channel flows at friction Reynolds number ($Re_{\unicode[STIX]{x1D70F}}$) up to $Re_{\unicode[STIX]{x1D70F}}=5200$. Each term in the transport equation has been spectrally decomposed to expose the contribution of turbulence at different length scales to the processes governing the flow of energy in the wall-normal direction, in scale and among components. The outer-layer turbulence is dominated by very large-scale streamwise elongated modes, which are consistent with the very large-scale motions (VLSM) that have been observed by many others. The presence of these VLSMs drives many of the characteristics of the turbulent energy flows. Away from the wall, production occurs primarily in these large-scale streamwise-elongated modes in the streamwise velocity, but dissipation occurs nearly isotropically in both velocity components and scale. For this to happen, the energy is transferred from the streamwise-elongated modes to modes with a range of orientations through nonlinear interactions, and then transferred to other velocity components. This allows energy to be transferred more-or-less isotropically from these large scales to the small scales at which dissipation occurs. The VLSMs also transfer energy to the wall region, resulting in a modulation of the autonomous near-wall dynamics and the observed Reynolds number dependence of the near-wall velocity variances. The near-wall energy flows are more complex, but are consistent with the well-known autonomous near-wall dynamics that gives rise to streaks and streamwise vortices. Through the overlap region between outer- and inner-layer turbulence, there is a self-similar structure to the energy flows. The VLSM production occurs at spanwise scales that grow with $y$. There is transport of energy away from the wall over a range of scales that grows with $y$. Moreover, there is transfer of energy to small dissipative scales which grows like $y^{1/4}$, as expected from Kolmogorov scaling. Finally, the small-scale near-wall processes characterised by wavelengths less than 1000 wall units are largely Reynolds number independent, while the larger-scale outer-layer processes are strongly Reynolds number dependent. The interaction between them appears to be relatively simple.
Leisingite, Cu(Mg,Cu,Fe,Zn)2Te6+O6·6H2O, a new mineral species from the Centennial Eureka mine, Juab County, Utah
- Andrew C. Roberts, Lee A. Groat, Joel D. Grice, Robert A. Gault, Martin C. Jensen, Elizabeth A. Moffatt, John A. R. Stirling
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- Journal:
- Mineralogical Magazine / Volume 60 / Issue 401 / August 1996
- Published online by Cambridge University Press:
- 05 July 2018, pp. 653-657
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Leisingite, ideally Cu(Mg,Cu,Fe,Zn)2Te6+O6·6H2O, is hexagonal, P3 (143), with unit-cell parameters refined from powder data: a = 5.305(1), c = 9.693(6) Å, V = 236.2(2) Å3, c/a = 1.8271, Z = 1. The strongest six reflections of the X-ray powder-diffraction pattern [d in Å (I) (hkl)] are: 9.70 (100) (001), 4.834 (80) (002), 4.604 (60) (100), 2.655 (60) (110), 2.556 (70) (111) and 2.326 (70) (112). The mineral is found on the dumps of the Centennial Eureka mine, Juab County, Utah U.S.A. where it occurs as isolated, or rarely as clusters of, hexagonal-shaped very thin plates or foliated masses in small vugs of crumbly to drusy white to colourless quartz. Associated minerals are jensenite, cesbronite and hematite. Individual crystals are subhedral to euhedral and average less than 0.1 mm in size. Cleavage {001} perfect. Forms are: {001} major; {100}, {110} minute. The mineral is transparent to somewhat translucent, pale yellow to pale orange-yellow, with a pale yellow streak and an uneven fracture. Leisingite is vitreous with a somewhat satiny to frosted appearance, brittle to somewhat flexible and nonfluorescent; H(Mohs) 3–4; D(calc.) 3.41 for the idealized formula; uniaxial negative, ω = 1.803(3), ɛ = 1.581 (calc.). Averaged electron-microprobe analyses yielded CuO 24.71, FeO 6.86, MgO 6.19, ZnO 0.45, TeO3 36.94, H2O (calc.) [21.55], total [96.70] wt.%, leading to the empirical formula based on O = 12. The infrared absorption spectrum shows definite bands for structural H2O with an O-H stretching frequency centered at 3253 cm−1 and a H-O-H flexing frequency centered at 1670 cm−l. The mineral name honours Joseph F. Leising, Reno, Nevada, who helped collect the discovery specimens.
Near-infrared spectroscopy used to predict soybean seed germination and vigour
- Maythem Al-Amery, Robert L. Geneve, Mauricio F. Sanches, Paul R. Armstrong, Elizabeth B. Maghirang, Chad Lee, Roberval D. Vieira, David F. Hildebrand
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- Journal:
- Seed Science Research / Volume 28 / Issue 3 / September 2018
- Published online by Cambridge University Press:
- 11 May 2018, pp. 245-252
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Rapid, non-destructive methods for measuring seed germination and vigour are valuable. Standard germination and seed vigour were determined using 81 soybean seed lots. From these data, seed lots were separated into high and low germinating seed lots as well as high, medium and low vigour seed lots. Near-infrared spectra (950–1650 nm) were collected for training and validation samples for each seed category and used to create partial least squares (PLS) prediction models. For both germination and vigour, qualitative models provided better discrimination of high and low performing seed lots compared with quantitative models. The qualitative germination prediction models correctly identified low and high germination seed lots with an accuracy between 85.7 and 89.7%. For seed vigour, qualitative predictions for the 3-category (low, medium and high vigour) models could not adequately separate high and medium vigour seeds. However, the 2-category (low, medium plus high vigour) prediction models could correctly identify low vigour seed lots between 80 and 100% and the medium plus high vigour seed lots between 96.3 and 96.6%. To our knowledge, the current study is the first to provide near-infrared spectroscopy (NIRS)-based predictive models using agronomically meaningful cut-offs for standard germination and vigour on a commercial scale using over 80 seed lots.
Allocation of attention to scenes of peer harassment: Visual–cognitive moderators of the link between peer victimization and aggression
- Wendy Troop-Gordon, Robert D. Gordon, Bethany M. Schwandt, Gregor A. Horvath, Elizabeth Ewing Lee, Kari J. Visconti
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- Journal:
- Development and Psychopathology / Volume 31 / Issue 2 / May 2019
- Published online by Cambridge University Press:
- 22 March 2018, pp. 525-540
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As approximately one-third of peer-victimized children evidence heightened aggression (Schwartz, Proctor, & Chien, 2001), it is imperative to identify the circumstances under which victimization and aggression co-develop. The current study explored two potential moderators of victimization–aggression linkages: (a) attentional bias toward cues signaling threat and (b) attentional bais toward cues communicating interpersonal support. Seventy-two fifth- and sixth-grade children (34 boys; Mage = 11.67) were eye tracked while watching video clips of bullying. Each scene included a bully, a victim, a reinforcer, and a defender. Children's victimization was measured using peer, parent, and teacher reports. Aggression was measured using peer reports of overt and relational aggression and teacher reports of aggression. Victimization was associated with greater aggression at high levels of attention to the bully. Victimization was also associated with greater aggression at low attention to the defender for boys, but at high attention to the defender for girls. Attention to the victim was negatively correlated with aggression regardless of victimization history. Thus, attentional biases to social cues integral to the bullying context differentiate whether victimization is linked to aggression, necessitating future research on the development of these biases and concurrent trajectories of sociobehavioral development.
Extreme-scale motions in turbulent plane Couette flows
- Myoungkyu Lee, Robert D. Moser
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- Journal:
- Journal of Fluid Mechanics / Volume 842 / 10 May 2018
- Published online by Cambridge University Press:
- 06 March 2018, pp. 128-145
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We study the large-scale motions in turbulent plane Couette flows at moderate friction Reynolds number up to $Re_{\unicode[STIX]{x1D70F}}=500$. Direct numerical simulation (DNS) domains were as large as $100\unicode[STIX]{x03C0}\unicode[STIX]{x1D6FF}\times 2\unicode[STIX]{x1D6FF}\times 5\unicode[STIX]{x03C0}\unicode[STIX]{x1D6FF}$, where $\unicode[STIX]{x1D6FF}$ is half the distance between the walls. The results indicate that there are streamwise vortices filling the space between the walls that remain correlated over distances in the streamwise direction and that increase strongly with the Reynolds number, so that for the largest Reynolds number studied here, they are correlated across the entire $100\unicode[STIX]{x03C0}\unicode[STIX]{x1D6FF}$ length of the domain. The presence of these very long structures is apparent in the spectra of all three velocity components and the Reynolds stress. In DNS using a smaller domain, the large structures are constrained, eliminating the streamwise variations present in the larger domain. Near the centre of the domain, these large-scale structures contribute as much as half of the Reynolds shear stress.
Education in Twins and Their Parents Across Birth Cohorts Over 100 years: An Individual-Level Pooled Analysis of 42-Twin Cohorts
- Karri Silventoinen, Aline Jelenkovic, Antti Latvala, Reijo Sund, Yoshie Yokoyama, Vilhelmina Ullemar, Catarina Almqvist, Catherine A. Derom, Robert F. Vlietinck, Ruth J. F. Loos, Christian Kandler, Chika Honda, Fujio Inui, Yoshinori Iwatani, Mikio Watanabe, Esther Rebato, Maria A. Stazi, Corrado Fagnani, Sonia Brescianini, Yoon-Mi Hur, Hoe-Uk Jeong, Tessa L. Cutler, John L. Hopper, Andreas Busjahn, Kimberly J. Saudino, Fuling Ji, Feng Ning, Zengchang Pang, Richard J. Rose, Markku Koskenvuo, Kauko Heikkilä, Wendy Cozen, Amie E. Hwang, Thomas M. Mack, Sisira H. Siribaddana, Matthew Hotopf, Athula Sumathipala, Fruhling Rijsdijk, Joohon Sung, Jina Kim, Jooyeon Lee, Sooji Lee, Tracy L. Nelson, Keith E. Whitfield, Qihua Tan, Dongfeng Zhang, Clare H. Llewellyn, Abigail Fisher, S. Alexandra Burt, Kelly L. Klump, Ariel Knafo-Noam, David Mankuta, Lior Abramson, Sarah E. Medland, Nicholas G. Martin, Grant W. Montgomery, Patrik K. E. Magnusson, Nancy L. Pedersen, Anna K. Dahl Aslan, Robin P. Corley, Brooke M. Huibregtse, Sevgi Y. Öncel, Fazil Aliev, Robert F. Krueger, Matt McGue, Shandell Pahlen, Gonneke Willemsen, Meike Bartels, Catharina E. M. van Beijsterveldt, Judy L. Silberg, Lindon J. Eaves, Hermine H. Maes, Jennifer R. Harris, Ingunn Brandt, Thomas S. Nilsen, Finn Rasmussen, Per Tynelius, Laura A. Baker, Catherine Tuvblad, Juan R. Ordoñana, Juan F. Sánchez-Romera, Lucia Colodro-Conde, Margaret Gatz, David A. Butler, Paul Lichtenstein, Jack H. Goldberg, K. Paige Harden, Elliot M. Tucker-Drob, Glen E. Duncan, Dedra Buchwald, Adam D. Tarnoki, David L. Tarnoki, Carol E. Franz, William S. Kremen, Michael J. Lyons, José A. Maia, Duarte L. Freitas, Eric Turkheimer, Thorkild I. A. Sørensen, Dorret I. Boomsma, Jaakko Kaprio
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- Journal:
- Twin Research and Human Genetics / Volume 20 / Issue 5 / October 2017
- Published online by Cambridge University Press:
- 04 October 2017, pp. 395-405
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Whether monozygotic (MZ) and dizygotic (DZ) twins differ from each other in a variety of phenotypes is important for genetic twin modeling and for inferences made from twin studies in general. We analyzed whether there were differences in individual, maternal and paternal education between MZ and DZ twins in a large pooled dataset. Information was gathered on individual education for 218,362 adult twins from 27 twin cohorts (53% females; 39% MZ twins), and on maternal and paternal education for 147,315 and 143,056 twins respectively, from 28 twin cohorts (52% females; 38% MZ twins). Together, we had information on individual or parental education from 42 twin cohorts representing 19 countries. The original education classifications were transformed to education years and analyzed using linear regression models. Overall, MZ males had 0.26 (95% CI [0.21, 0.31]) years and MZ females 0.17 (95% CI [0.12, 0.21]) years longer education than DZ twins. The zygosity difference became smaller in more recent birth cohorts for both males and females. Parental education was somewhat longer for fathers of DZ twins in cohorts born in 1990–1999 (0.16 years, 95% CI [0.08, 0.25]) and 2000 or later (0.11 years, 95% CI [0.00, 0.22]), compared with fathers of MZ twins. The results show that the years of both individual and parental education are largely similar in MZ and DZ twins. We suggest that the socio-economic differences between MZ and DZ twins are so small that inferences based upon genetic modeling of twin data are not affected.
Formulations of Fusarium oxysporum f.sp. erythroxyli for biocontrol of Erythroxylum coca var. coca
- Bryan A. Bailey, K. Prakash Hebbar, Mary Strem, Robert D. Lumsden, Lee C. Darlington, William J. Connick, Jr., D. J. Daigle
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- Journal:
- Weed Science / Volume 46 / Issue 6 / December 1998
- Published online by Cambridge University Press:
- 12 June 2017, pp. 682-689
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Formulations of Fusarium oxysporum Schlechtend:Fr. f.sp. erythroxyli isolate EN-4, pathogenic to Erythroxylum coca var. coca (coca) were evaluated in greenhouse and field studies to determine their relative ability to enhance pathogen populations in the soil or cause disease in coca. The formulations rice-alginate prill, Pesta, and C6 were most thoroughly tested and are products of three formulation processes. The formulations were applied in the greenhouse and field at 33.6 kg ha−1. All the formulations tested enhanced the population of EN-4 in the soil during greenhouse (> 6 wk) and field (> 7 mo) experiments. EN-4 was present in the upper 1 cm of formulation-treated soil at > 200-fold higher populations than established below a depth of 7 to 10 cm in both greenhouse and field experiments. This population distribution was maintained throughout the 7-mo sampling period for field experiments. The enhanced soil populations of EN-4 were associated with an increase in root colonization by the pathogen EN-4 in the field 5 to 7 mo after treatment. The formulated F. oxysporum began to have a significant effect on plant death 100 to 200 d after application in two of three field experiments, based on repeated measures analysis. The various formulations tested tended to establish similar pathogen populations in soil and subsequently caused similar levels of disease. The primary factors influencing formulation performance may be environmental, since inoculum production is dependent on sporulation of the formulation, which, although rapid, may continue over several weeks subsequent to application.