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Empowering the Participant Voice (EPV): Design and implementation of collaborative infrastructure to collect research participant experience feedback at scale
- Rhonda G. Kost, Alex Cheng, Joseph Andrews, Ranee Chatterjee, Ann Dozier, Daniel Ford, Natalie Schlesinger, Carrie Dykes, Issis Kelly-Pumarol, Nan Kennedy, Cassie Lewis-Land, Sierra Lindo, Liz Martinez, Michael Musty, Jamie Roberts, Roger Vaughan, Lynne Wagenknecht, Scott Carey, Cameron Coffran, James Goodrich, Pavithra Panjala, Sameer Cheema, Adam Qureshi, Ellis Thomas, Lindsay O’Neill, Eva Bascompte-Moragas, Paul Harris
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- Journal:
- Journal of Clinical and Translational Science / Volume 8 / Issue 1 / 2024
- Published online by Cambridge University Press:
- 06 February 2024, e40
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Empowering the Participant Voice (EPV) is an NCATS-funded six-CTSA collaboration to develop, demonstrate, and disseminate a low-cost infrastructure for collecting timely feedback from research participants, fostering trust, and providing data for improving clinical translational research. EPV leverages the validated Research Participant Perception Survey (RPPS) and the popular REDCap electronic data-capture platform. This report describes the development of infrastructure designed to overcome identified institutional barriers to routinely collecting participant feedback using RPPS and demonstration use cases. Sites engaged local stakeholders iteratively, incorporating feedback about anticipated value and potential concerns into project design. The team defined common standards and operations, developed software, and produced a detailed planning and implementation Guide. By May 2023, 2,575 participants diverse in age, race, ethnicity, and sex had responded to approximately 13,850 survey invitations (18.6%); 29% of responses included free-text comments. EPV infrastructure enabled sites to routinely access local and multi-site research participant experience data on an interactive analytics dashboard. The EPV learning collaborative continues to test initiatives to improve survey reach and optimize infrastructure and process. Broad uptake of EPV will expand the evidence base, enable hypothesis generation, and drive research-on-research locally and nationally to enhance the clinical research enterprise.
Sorption of Nitroaromatics by Ammonium- and Organic Ammonium-Exchanged Smectite: Shifts from Adsorption/Complexation to a Partition-Dominated Process
- Michael G. Roberts, Hui Li, Brian J. Teppen, Stephen A. Boyd
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- Journal:
- Clays and Clay Minerals / Volume 54 / Issue 4 / August 2006
- Published online by Cambridge University Press:
- 01 January 2024, pp. 426-434
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Nitroaromatic compounds (NACs) are components of munitions commonly found as soil contaminants at military training sites and elsewhere. These compounds pose possible threats to human health and ecological systems. Recent studies indicate that these compounds are strongly retained by smectite clays. The adsorption mechanisms are not fully reconciled, but it is known that the type of exchangeable cation strongly affects NAC affinity for smectites. This study examined the sorption of 1,3-dinitrobenzene, 2,4-dinitrotoluene and naphthalene from water by a smectite clay (SWy-2) saturated with ammonium, tetramethylammonium (TMA), trimethylphenylammonium (TMPA) and hexadecyltrimethylammonium (HDTMA). In all cases, we observed greater sorption of 2,4-dinitrotoluene compared with 1,3-dinitrobenzene. The sorption isotherms for 2,4-dinitrotoluene and 1,3-dinitrobenzene displayed a concave-downward curve for NH4-SWy-2 and TMA-SWy-2, whereas the isotherms for sorption of HDTMA-SWy-2 and TMPA-SWy-2 were essentially linear. The magnitude of sorption followed the order: NH4-SWy-2 > TMA-SWy-2 > TMPA-SWy-2 > HDTMA-SWy-2 for both compounds. The greater affinity of NACs for NH4- and TMA-SWy-2 is due in part to complex formation between the exchangeable cation and −NO2 groups. These clays also provide near optimal interlayer distances that approximate the molecular thickness of NACs hence promoting the simultaneous interaction of the planar aromatic rings with opposing siloxane surfaces and solute dehydration. Both processes are energetically favorable. In HDTMA-SWy-2, sorption of all solutes is via a partition-dominated process. Solute competition (diminished uptake of one solute in the presence of a second) was observed for TMA-SWy-2 but not HDTMA-SWy-2. This is consistent with an adsorptive mechanism for TMA-SWy-2 and a partitioning mechanism for HDTMA-SWy-2. This study demonstrates that the dominant molecular mechanism of NAC sorption by smectite changes fundamentally from complexation between −NO2 groups and the exchangeable cation (viz. NH4 and TMA) to partitioning for a systematic series of ammonium and quaternary ammonium cations in which the locus of positive charge (the central N atom) is progressively shielded by organic moieties of increasing size.
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.
Radiofrequency ice dielectric measurements at Summit Station, Greenland
- Juan Antonio Aguilar, Patrick Allison, Dave Besson, Abby Bishop, Olga Botner, Sjoerd Bouma, Stijn Buitink, Maddalena Cataldo, Brian A. Clark, Kenny Couberly, Zach Curtis-Ginsberg, Paramita Dasgupta, Simon de Kockere, Krijn D. de Vries, Cosmin Deaconu, Michael A. DuVernois, Anna Eimer, Christian Glaser, Allan Hallgren, Steffen Hallmann, Jordan Christian Hanson, Bryan Hendricks, Jakob Henrichs, Nils Heyer, Christian Hornhuber, Kaeli Hughes, Timo Karg, Albrecht Karle, John L. Kelley, Michael Korntheuer, Marek Kowalski, Ilya Kravchenko, Ryan Krebs, Robert Lahmann, Uzair Latif, Joseph Mammo, Matthew J. Marsee, Zachary S. Meyers, Kelli Michaels, Katharine Mulrey, Marco Muzio, Anna Nelles, Alexander Novikov, Alisa Nozdrina, Eric Oberla, Bob Oeyen, Ilse Plaisier, Noppadol Punsuebsay, Lilly Pyras, Dirk Ryckbosch, Olaf Scholten, David Seckel, Mohammad Ful Hossain Seikh, Daniel Smith, Jethro Stoffels, Daniel Southall, Karen Terveer, Simona Toscano, Delia Tosi, Dieder J. Van Den Broeck, Nick van Eijndhoven, Abigail G. Vieregg, Janna Z. Vischer, Christoph Welling, Dawn R. Williams, Stephanie Wissel, Robert Young, Adrian Zink
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- Journal:
- Journal of Glaciology , First View
- Published online by Cambridge University Press:
- 09 October 2023, pp. 1-12
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We recently reported on the radio-frequency attenuation length of cold polar ice at Summit Station, Greenland, based on bi-static radar measurements of radio-frequency bedrock echo strengths taken during the summer of 2021. Those data also allow studies of (a) the relative contributions of coherent (such as discrete internal conducting layers with sub-centimeter transverse scale) vs incoherent (e.g. bulk volumetric) scattering, (b) the magnitude of internal layer reflection coefficients, (c) limits on signal propagation velocity asymmetries (‘birefringence’) and (d) limits on signal dispersion in-ice over a bandwidth of ~100 MHz. We find that (1) attenuation lengths approach 1 km in our band, (2) after averaging 10 000 echo triggers, reflected signals observable over the thermal floor (to depths of ~1500 m) are consistent with being entirely coherent, (3) internal layer reflectivities are ≈–60$\to$–70 dB, (4) birefringent effects for vertically propagating signals are smaller by an order of magnitude relative to South Pole and (5) within our experimental limits, glacial ice is non-dispersive over the frequency band relevant for neutrino detection experiments.
Agricultural Research Service Weed Science Research: Past, Present, and Future
- Stephen L. Young, James V. Anderson, Scott R. Baerson, Joanna Bajsa-Hirschel, Dana M. Blumenthal, Chad S. Boyd, Clyde D. Boyette, Eric B. Brennan, Charles L. Cantrell, Wun S. Chao, Joanne C. Chee-Sanford, Charlie D. Clements, F. Allen Dray, Stephen O. Duke, Kayla M. Eason, Reginald S. Fletcher, Michael R. Fulcher, John F. Gaskin, Brenda J. Grewell, Erik P. Hamerlynck, Robert E. Hoagland, David P. Horvath, Eugene P. Law, John D. Madsen, Daniel E. Martin, Clint Mattox, Steven B. Mirsky, William T. Molin, Patrick J. Moran, Rebecca C. Mueller, Vijay K. Nandula, Beth A. Newingham, Zhiqiang Pan, Lauren M. Porensky, Paul D. Pratt, Andrew J. Price, Brian G. Rector, Krishna N. Reddy, Roger L. Sheley, Lincoln Smith, Melissa C. Smith, Keirith A. Snyder, Matthew A. Tancos, Natalie M. West, Gregory S. Wheeler, Martin M. Williams, Julie Wolf, Carissa L. Wonkka, Alice A. Wright, Jing Xi, Lew H. Ziska
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- Journal:
- Weed Science / Volume 71 / Issue 4 / July 2023
- Published online by Cambridge University Press:
- 16 August 2023, pp. 312-327
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The U.S. Department of Agriculture–Agricultural Research Service (USDA-ARS) has been a leader in weed science research covering topics ranging from the development and use of integrated weed management (IWM) tactics to basic mechanistic studies, including biotic resistance of desirable plant communities and herbicide resistance. ARS weed scientists have worked in agricultural and natural ecosystems, including agronomic and horticultural crops, pastures, forests, wild lands, aquatic habitats, wetlands, and riparian areas. Through strong partnerships with academia, state agencies, private industry, and numerous federal programs, ARS weed scientists have made contributions to discoveries in the newest fields of robotics and genetics, as well as the traditional and fundamental subjects of weed–crop competition and physiology and integration of weed control tactics and practices. Weed science at ARS is often overshadowed by other research topics; thus, few are aware of the long history of ARS weed science and its important contributions. This review is the result of a symposium held at the Weed Science Society of America’s 62nd Annual Meeting in 2022 that included 10 separate presentations in a virtual Weed Science Webinar Series. The overarching themes of management tactics (IWM, biological control, and automation), basic mechanisms (competition, invasive plant genetics, and herbicide resistance), and ecosystem impacts (invasive plant spread, climate change, conservation, and restoration) represent core ARS weed science research that is dynamic and efficacious and has been a significant component of the agency’s national and international efforts. This review highlights current studies and future directions that exemplify the science and collaborative relationships both within and outside ARS. Given the constraints of weeds and invasive plants on all aspects of food, feed, and fiber systems, there is an acknowledged need to face new challenges, including agriculture and natural resources sustainability, economic resilience and reliability, and societal health and well-being.
DRAGON-Data: a platform and protocol for integrating genomic and phenotypic data across large psychiatric cohorts
- Amy J. Lynham, Sarah Knott, Jack F. G. Underwood, Leon Hubbard, Sharifah S. Agha, Jonathan I. Bisson, Marianne B. M. van den Bree, Samuel J. R. A. Chawner, Nicholas Craddock, Michael O'Donovan, Ian R. Jones, George Kirov, Kate Langley, Joanna Martin, Frances Rice, Neil P. Roberts, Anita Thapar, Richard Anney, Michael J. Owen, Jeremy Hall, Antonio F. Pardiñas, James T. R. Walters
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- Journal:
- BJPsych Open / Volume 9 / Issue 2 / March 2023
- Published online by Cambridge University Press:
- 08 February 2023, e32
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Background
Current psychiatric diagnoses, although heritable, have not been clearly mapped onto distinct underlying pathogenic processes. The same symptoms often occur in multiple disorders, and a substantial proportion of both genetic and environmental risk factors are shared across disorders. However, the relationship between shared symptoms and shared genetic liability is still poorly understood.
AimsWell-characterised, cross-disorder samples are needed to investigate this matter, but few currently exist. Our aim is to develop procedures to purposely curate and aggregate genotypic and phenotypic data in psychiatric research.
MethodAs part of the Cardiff MRC Mental Health Data Pathfinder initiative, we have curated and harmonised phenotypic and genetic information from 15 studies to create a new data repository, DRAGON-Data. To date, DRAGON-Data includes over 45 000 individuals: adults and children with neurodevelopmental or psychiatric diagnoses, affected probands within collected families and individuals who carry a known neurodevelopmental risk copy number variant.
ResultsWe have processed the available phenotype information to derive core variables that can be reliably analysed across groups. In addition, all data-sets with genotype information have undergone rigorous quality control, imputation, copy number variant calling and polygenic score generation.
ConclusionsDRAGON-Data combines genetic and non-genetic information, and is available as a resource for research across traditional psychiatric diagnostic categories. Algorithms and pipelines used for data harmonisation are currently publicly available for the scientific community, and an appropriate data-sharing protocol will be developed as part of ongoing projects (DATAMIND) in partnership with Health Data Research UK.
Cross-cultural support for a link between analytic thinking and disbelief in God: Evidence from India and the United Kingdom
- Michael N. Stagnaro, Robert M. Ross, Gordon Pennycook, David G. Rand
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- Journal:
- Judgment and Decision Making / Volume 14 / Issue 2 / March 2019
- Published online by Cambridge University Press:
- 01 January 2023, pp. 179-186
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A substantial body of evidence suggests that favoring reason over intuition (employing an analytic cognitive style) is associated with reduced belief in God. In the current work, we address outstanding issues in this literature with two studies examining the relationship between analytic cognitive style (as measured by performance on the Cognitive Reflection Test) and belief in God. First, prior research focused on Judeo-Christian cultures, and it is uncertain whether the results generalize to other religious systems or beliefs. Study 1 helps to address this question by documenting a negative correlation between CRT performance and belief in God, r = −.18, in a sample of 513 participants from India, a majority Hindu country. Second, among 150 participants from the United Kingdom, Gervais et al. (2018) reported the first and (to date) only evidence for a positive relationship between CRT and belief in God. In Study 2, we assess the robustness of this result by recruiting 547 participants from the United Kingdom. Unlike Gervais et al., using the same items, we find a negative correlation between CRT and belief in God (r = −.19). Our results add further support to the argument that analytic thinking undermines belief in God.
The Hierarchical Taxonomy of Psychopathology (HiTOP) in psychiatric practice and research
- Roman Kotov, David C. Cicero, Christopher C. Conway, Colin G. DeYoung, Alexandre Dombrovski, Nicholas R. Eaton, Michael B. First, Miriam K. Forbes, Steven E. Hyman, Katherine G. Jonas, Robert F. Krueger, Robert D. Latzman, James J. Li, Brady D. Nelson, Darrel A. Regier, Craig Rodriguez-Seijas, Camilo J. Ruggero, Leonard J. Simms, Andrew E. Skodol, Irwin D. Waldman, Monika A. Waszczuk, David Watson, Thomas A. Widiger, Sylia Wilson, Aidan G. C. Wright
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- Journal:
- Psychological Medicine / Volume 52 / Issue 9 / July 2022
- Published online by Cambridge University Press:
- 02 June 2022, pp. 1666-1678
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The Hierarchical Taxonomy of Psychopathology (HiTOP) has emerged out of the quantitative approach to psychiatric nosology. This approach identifies psychopathology constructs based on patterns of co-variation among signs and symptoms. The initial HiTOP model, which was published in 2017, is based on a large literature that spans decades of research. HiTOP is a living model that undergoes revision as new data become available. Here we discuss advantages and practical considerations of using this system in psychiatric practice and research. We especially highlight limitations of HiTOP and ongoing efforts to address them. We describe differences and similarities between HiTOP and existing diagnostic systems. Next, we review the types of evidence that informed development of HiTOP, including populations in which it has been studied and data on its validity. The paper also describes how HiTOP can facilitate research on genetic and environmental causes of psychopathology as well as the search for neurobiologic mechanisms and novel treatments. Furthermore, we consider implications for public health programs and prevention of mental disorders. We also review data on clinical utility and illustrate clinical application of HiTOP. Importantly, the model is based on measures and practices that are already used widely in clinical settings. HiTOP offers a way to organize and formalize these techniques. This model already can contribute to progress in psychiatry and complement traditional nosologies. Moreover, HiTOP seeks to facilitate research on linkages between phenotypes and biological processes, which may enable construction of a system that encompasses both biomarkers and precise clinical description.
Using polygenic scores and clinical data for bipolar disorder patient stratification and lithium response prediction: machine learning approach – CORRIGENDUM
- Micah Cearns, Azmeraw T. Amare, Klaus Oliver Schubert, Anbupalam Thalamuthu, Joseph Frank, Fabian Streit, Mazda Adli, Nirmala Akula, Kazufumi Akiyama, Raffaella Ardau, Bárbara Arias, JeanMichel Aubry, Lena Backlund, Abesh Kumar Bhattacharjee, Frank Bellivier, Antonio Benabarre, Susanne Bengesser, Joanna M. Biernacka, Armin Birner, Clara Brichant-Petitjean, Pablo Cervantes, HsiChung Chen, Caterina Chillotti, Sven Cichon, Cristiana Cruceanu, Piotr M. Czerski, Nina Dalkner, Alexandre Dayer, Franziska Degenhardt, Maria Del Zompo, J. Raymond DePaulo, Bruno Étain, Peter Falkai, Andreas J. Forstner, Louise Frisen, Mark A. Frye, Janice M. Fullerton, Sébastien Gard, Julie S. Garnham, Fernando S. Goes, Maria Grigoroiu-Serbanescu, Paul Grof, Ryota Hashimoto, Joanna Hauser, Urs Heilbronner, Stefan Herms, Per Hoffmann, Andrea Hofmann, Liping Hou, Yi-Hsiang Hsu, Stephane Jamain, Esther Jiménez, Jean-Pierre Kahn, Layla Kassem, Po-Hsiu Kuo, Tadafumi Kato, John Kelsoe, Sarah Kittel-Schneider, Sebastian Kliwicki, Barbara König, Ichiro Kusumi, Gonzalo Laje, Mikael Landén, Catharina Lavebratt, Marion Leboyer, Susan G. Leckband, Mario Maj, the Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, Mirko Manchia, Lina Martinsson, Michael J. McCarthy, Susan McElroy, Francesc Colom, Marina Mitjans, Francis M. Mondimore, Palmiero Monteleone, Caroline M. Nievergelt, Markus M. Nöthen, Tomas Novák, Claire O'Donovan, Norio Ozaki, Vincent Millischer, Sergi Papiol, Andrea Pfennig, Claudia Pisanu, James B. Potash, Andreas Reif, Eva Reininghaus, Guy A. Rouleau, Janusz K. Rybakowski, Martin Schalling, Peter R. Schofield, Barbara W. Schweizer, Giovanni Severino, Tatyana Shekhtman, Paul D. Shilling, Katzutaka Shimoda, Christian Simhandl, Claire M. Slaney, Alessio Squassina, Thomas Stamm, Pavla Stopkova, Fasil TekolaAyele, Alfonso Tortorella, Gustavo Turecki, Julia Veeh, Eduard Vieta, Stephanie H. Witt, Gloria Roberts, Peter P. Zandi, Martin Alda, Michael Bauer, Francis J. McMahon, Philip B. Mitchell, Thomas G. Schulze, Marcella Rietschel, Scott R. Clark, Bernhard T. Baune
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- Journal:
- The British Journal of Psychiatry / Volume 221 / Issue 2 / August 2022
- Published online by Cambridge University Press:
- 04 May 2022, p. 494
- Print publication:
- August 2022
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Using polygenic scores and clinical data for bipolar disorder patient stratification and lithium response prediction: machine learning approach
- Micah Cearns, Azmeraw T. Amare, Klaus Oliver Schubert, Anbupalam Thalamuthu, Joseph Frank, Fabian Streit, Mazda Adli, Nirmala Akula, Kazufumi Akiyama, Raffaella Ardau, Bárbara Arias, Jean-Michel Aubry, Lena Backlund, Abesh Kumar Bhattacharjee, Frank Bellivier, Antonio Benabarre, Susanne Bengesser, Joanna M. Biernacka, Armin Birner, Clara Brichant-Petitjean, Pablo Cervantes, Hsi-Chung Chen, Caterina Chillotti, Sven Cichon, Cristiana Cruceanu, Piotr M. Czerski, Nina Dalkner, Alexandre Dayer, Franziska Degenhardt, Maria Del Zompo, J. Raymond DePaulo, Bruno Étain, Peter Falkai, Andreas J. Forstner, Louise Frisen, Mark A. Frye, Janice M. Fullerton, Sébastien Gard, Julie S. Garnham, Fernando S. Goes, Maria Grigoroiu-Serbanescu, Paul Grof, Ryota Hashimoto, Joanna Hauser, Urs Heilbronner, Stefan Herms, Per Hoffmann, Andrea Hofmann, Liping Hou, Yi-Hsiang Hsu, Stephane Jamain, Esther Jiménez, Jean-Pierre Kahn, Layla Kassem, Po-Hsiu Kuo, Tadafumi Kato, John Kelsoe, Sarah Kittel-Schneider, Sebastian Kliwicki, Barbara König, Ichiro Kusumi, Gonzalo Laje, Mikael Landén, Catharina Lavebratt, Marion Leboyer, Susan G. Leckband, Mario Maj, the Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, Mirko Manchia, Lina Martinsson, Michael J. McCarthy, Susan McElroy, Francesc Colom, Marina Mitjans, Francis M. Mondimore, Palmiero Monteleone, Caroline M. Nievergelt, Markus M. Nöthen, Tomas Novák, Claire O'Donovan, Norio Ozaki, Vincent Millischer, Sergi Papiol, Andrea Pfennig, Claudia Pisanu, James B. Potash, Andreas Reif, Eva Reininghaus, Guy A. Rouleau, Janusz K. Rybakowski, Martin Schalling, Peter R. Schofield, Barbara W. Schweizer, Giovanni Severino, Tatyana Shekhtman, Paul D. Shilling, Katzutaka Shimoda, Christian Simhandl, Claire M. Slaney, Alessio Squassina, Thomas Stamm, Pavla Stopkova, Fasil Tekola-Ayele, Alfonso Tortorella, Gustavo Turecki, Julia Veeh, Eduard Vieta, Stephanie H. Witt, Gloria Roberts, Peter P. Zandi, Martin Alda, Michael Bauer, Francis J. McMahon, Philip B. Mitchell, Thomas G. Schulze, Marcella Rietschel, Scott R. Clark, Bernhard T. Baune
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- Journal:
- The British Journal of Psychiatry / Volume 220 / Issue 4 / April 2022
- Published online by Cambridge University Press:
- 28 February 2022, pp. 219-228
- Print publication:
- April 2022
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Background
Response to lithium in patients with bipolar disorder is associated with clinical and transdiagnostic genetic factors. The predictive combination of these variables might help clinicians better predict which patients will respond to lithium treatment.
AimsTo use a combination of transdiagnostic genetic and clinical factors to predict lithium response in patients with bipolar disorder.
MethodThis study utilised genetic and clinical data (n = 1034) collected as part of the International Consortium on Lithium Genetics (ConLi+Gen) project. Polygenic risk scores (PRS) were computed for schizophrenia and major depressive disorder, and then combined with clinical variables using a cross-validated machine-learning regression approach. Unimodal, multimodal and genetically stratified models were trained and validated using ridge, elastic net and random forest regression on 692 patients with bipolar disorder from ten study sites using leave-site-out cross-validation. All models were then tested on an independent test set of 342 patients. The best performing models were then tested in a classification framework.
ResultsThe best performing linear model explained 5.1% (P = 0.0001) of variance in lithium response and was composed of clinical variables, PRS variables and interaction terms between them. The best performing non-linear model used only clinical variables and explained 8.1% (P = 0.0001) of variance in lithium response. A priori genomic stratification improved non-linear model performance to 13.7% (P = 0.0001) and improved the binary classification of lithium response. This model stratified patients based on their meta-polygenic loadings for major depressive disorder and schizophrenia and was then trained using clinical data.
ConclusionsUsing PRS to first stratify patients genetically and then train machine-learning models with clinical predictors led to large improvements in lithium response prediction. When used with other PRS and biological markers in the future this approach may help inform which patients are most likely to respond to lithium treatment.
A reconsideration of university gap funds for promoting biomedical entrepreneurship
- Everett G. Hall, Thomas M. Krenning, Robert J. Reardon, Emre Toker, Michael S. Kinch
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- Journal:
- Journal of Clinical and Translational Science / Volume 6 / Issue 1 / 2022
- Published online by Cambridge University Press:
- 31 January 2022, e28
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The last 50 years have seen an increasing dependence on academic institutions to develop and commercialize new biomedical innovations, a responsibility for which many universities are ill-equipped. To address this need, we created LEAP, an asset development and gap fund program at Washington University in St. Louis (WUSTL). Beyond awarding funds to promising projects, this program aimed to promote a culture of academic entrepreneurship, and thus improve WUSTL technology transfer, by providing university inventors with individualized consulting and industry expert feedback. The purpose of this work is to document the structure of the LEAP program and evaluate its impact on the WUSTL entrepreneurial ecosystem. Our analysis utilizes program data, participant surveys, and WUSTL technology transfer office records to demonstrate that LEAP consistently attracted new investigators and that the training provided by the program was both impactful and highly valued by participants. We also show that an increase in annual WUSTL start-up formation during the years after LEAP was established and implicate the program in this increase. Taken together, our results illustrate that programs like LEAP could serve as a model for other institutions that seek to support academic entrepreneurship initiatives.
Chapter 18 - Combined Multi-portal “Pull-Through” Keyhole Craniotomy
- from Section II - Open Combined Approaches
- Edited by Vijay Agarwal
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- Book:
- Integrated Management of Complex Intracranial Lesions
- Published online:
- 05 October 2021
- Print publication:
- 21 October 2021, pp 187-195
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Summary
The definition of combined approaches is broad. This can include multiple portals to the same or different region in the skull base. The “pull-through technique is a versatile, dual-keyhole approach developed to attach tumors that extend between the temporal and occipital poles. This approach is complex, as it entails a knowledge of the intricate anatomy and eloquent cortical and subcortical structures in this region. This combined approach is tailed to minimize peripheral brain damage while providing a direct route to the pathology. This chapter discusses the indications, the anatomy, the patient selection, and the surgical nuances of this approach.
Characterisation of age and polarity at onset in bipolar disorder
- Janos L. Kalman, Loes M. Olde Loohuis, Annabel Vreeker, Andrew McQuillin, Eli A. Stahl, Douglas Ruderfer, Maria Grigoroiu-Serbanescu, Georgia Panagiotaropoulou, Stephan Ripke, Tim B. Bigdeli, Frederike Stein, Tina Meller, Susanne Meinert, Helena Pelin, Fabian Streit, Sergi Papiol, Mark J. Adams, Rolf Adolfsson, Kristina Adorjan, Ingrid Agartz, Sofie R. Aminoff, Heike Anderson-Schmidt, Ole A. Andreassen, Raffaella Ardau, Jean-Michel Aubry, Ceylan Balaban, Nicholas Bass, Bernhard T. Baune, Frank Bellivier, Antoni Benabarre, Susanne Bengesser, Wade H Berrettini, Marco P. Boks, Evelyn J. Bromet, Katharina Brosch, Monika Budde, William Byerley, Pablo Cervantes, Catina Chillotti, Sven Cichon, Scott R. Clark, Ashley L. Comes, Aiden Corvin, William Coryell, Nick Craddock, David W. Craig, Paul E. Croarkin, Cristiana Cruceanu, Piotr M. Czerski, Nina Dalkner, Udo Dannlowski, Franziska Degenhardt, Maria Del Zompo, J. Raymond DePaulo, Srdjan Djurovic, Howard J. Edenberg, Mariam Al Eissa, Torbjørn Elvsåshagen, Bruno Etain, Ayman H. Fanous, Frederike Fellendorf, Alessia Fiorentino, Andreas J. Forstner, Mark A. Frye, Janice M. Fullerton, Katrin Gade, Julie Garnham, Elliot Gershon, Michael Gill, Fernando S. Goes, Katherine Gordon-Smith, Paul Grof, Jose Guzman-Parra, Tim Hahn, Roland Hasler, Maria Heilbronner, Urs Heilbronner, Stephane Jamain, Esther Jimenez, Ian Jones, Lisa Jones, Lina Jonsson, Rene S. Kahn, John R. Kelsoe, James L. Kennedy, Tilo Kircher, George Kirov, Sarah Kittel-Schneider, Farah Klöhn-Saghatolislam, James A. Knowles, Thorsten M. Kranz, Trine Vik Lagerberg, Mikael Landen, William B. Lawson, Marion Leboyer, Qingqin S. Li, Mario Maj, Dolores Malaspina, Mirko Manchia, Fermin Mayoral, Susan L. McElroy, Melvin G. McInnis, Andrew M. McIntosh, Helena Medeiros, Ingrid Melle, Vihra Milanova, Philip B. Mitchell, Palmiero Monteleone, Alessio Maria Monteleone, Markus M. Nöthen, Tomas Novak, John I. Nurnberger, Niamh O'Brien, Kevin S. O'Connell, Claire O'Donovan, Michael C. O'Donovan, Nils Opel, Abigail Ortiz, Michael J. Owen, Erik Pålsson, Carlos Pato, Michele T. Pato, Joanna Pawlak, Julia-Katharina Pfarr, Claudia Pisanu, James B. Potash, Mark H Rapaport, Daniela Reich-Erkelenz, Andreas Reif, Eva Reininghaus, Jonathan Repple, Hélène Richard-Lepouriel, Marcella Rietschel, Kai Ringwald, Gloria Roberts, Guy Rouleau, Sabrina Schaupp, William A Scheftner, Simon Schmitt, Peter R. Schofield, K. Oliver Schubert, Eva C. Schulte, Barbara Schweizer, Fanny Senner, Giovanni Severino, Sally Sharp, Claire Slaney, Olav B. Smeland, Janet L. Sobell, Alessio Squassina, Pavla Stopkova, John Strauss, Alfonso Tortorella, Gustavo Turecki, Joanna Twarowska-Hauser, Marin Veldic, Eduard Vieta, John B. Vincent, Wei Xu, Clement C. Zai, Peter P. Zandi, Psychiatric Genomics Consortium (PGC) Bipolar Disorder Working Group, International Consortium on Lithium Genetics (ConLiGen), Colombia-US Cross Disorder Collaboration in Psychiatric Genetics, Arianna Di Florio, Jordan W. Smoller, Joanna M. Biernacka, Francis J. McMahon, Martin Alda, Bertram Müller-Myhsok, Nikolaos Koutsouleris, Peter Falkai, Nelson B. Freimer, Till F.M. Andlauer, Thomas G. Schulze, Roel A. Ophoff
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- Journal:
- The British Journal of Psychiatry / Volume 219 / Issue 6 / December 2021
- Published online by Cambridge University Press:
- 25 August 2021, pp. 659-669
- Print publication:
- December 2021
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Background
Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.
AimsTo examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
MethodGenome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.
ResultsEarlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.
ConclusionsAAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.
Prestige and content biases together shape the cultural transmission of narratives
- Richard E.W. Berl, Alarna N. Samarasinghe, Seán G. Roberts, Fiona M. Jordan, Michael C. Gavin
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- Journal:
- Evolutionary Human Sciences / Volume 3 / 2021
- Published online by Cambridge University Press:
- 29 July 2021, e42
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Cultural transmission biases such as prestige are thought to have been a primary driver in shaping the dynamics of human cultural evolution. However, few empirical studies have measured the importance of prestige relative to other effects, such as content biases present within the information being transmitted. Here, we report the findings of an experimental transmission study designed to compare the simultaneous effects of a model using a high- or low-prestige regional accent with the presence of narrative content containing social, survival, emotional, moral, rational, or counterintuitive information in the form of a creation story. Results from multimodel inference reveal that prestige is a significant factor in determining the salience and recall of information, but that several content biases, specifically social, survival, negative emotional, and biological counterintuitive information, are significantly more influential. Further, we find evidence that reliance on prestige cues may serve as a conditional learning strategy when no content cues are available. Our results demonstrate that content biases serve a vital and underappreciated role in cultural transmission and cultural evolution.
Social media summary: Storyteller and tale are both key to memorability, but some content is more important than the storyteller's prestige.
A history of high-power laser research and development in the United Kingdom
- Part of
- Colin N. Danson, Malcolm White, John R. M. Barr, Thomas Bett, Peter Blyth, David Bowley, Ceri Brenner, Robert J. Collins, Neal Croxford, A. E. Bucker Dangor, Laurence Devereux, Peter E. Dyer, Anthony Dymoke-Bradshaw, Christopher B. Edwards, Paul Ewart, Allister I. Ferguson, John M. Girkin, Denis R. Hall, David C. Hanna, Wayne Harris, David I. Hillier, Christopher J. Hooker, Simon M. Hooker, Nicholas Hopps, Janet Hull, David Hunt, Dino A. Jaroszynski, Mark Kempenaars, Helmut Kessler, Sir Peter L. Knight, Steve Knight, Adrian Knowles, Ciaran L. S. Lewis, Ken S. Lipton, Abby Littlechild, John Littlechild, Peter Maggs, Graeme P. A. Malcolm, OBE, Stuart P. D. Mangles, William Martin, Paul McKenna, Richard O. Moore, Clive Morrison, Zulfikar Najmudin, David Neely, Geoff H. C. New, Michael J. Norman, Ted Paine, Anthony W. Parker, Rory R. Penman, Geoff J. Pert, Chris Pietraszewski, Andrew Randewich, Nadeem H. Rizvi, Nigel Seddon, MBE, Zheng-Ming Sheng, David Slater, Roland A. Smith, Christopher Spindloe, Roy Taylor, Gary Thomas, John W. G. Tisch, Justin S. Wark, Colin Webb, S. Mark Wiggins, Dave Willford, Trevor Winstone
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- Journal:
- High Power Laser Science and Engineering / Volume 9 / 2021
- Published online by Cambridge University Press:
- 27 April 2021, e18
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The first demonstration of laser action in ruby was made in 1960 by T. H. Maiman of Hughes Research Laboratories, USA. Many laboratories worldwide began the search for lasers using different materials, operating at different wavelengths. In the UK, academia, industry and the central laboratories took up the challenge from the earliest days to develop these systems for a broad range of applications. This historical review looks at the contribution the UK has made to the advancement of the technology, the development of systems and components and their exploitation over the last 60 years.
4 - Five Decades of Modeling Supporting the Systems Ecology Paradigm
- Edited by Robert G. Woodmansee, Colorado State University, John C. Moore, Colorado State University, Dennis S. Ojima, Colorado State University, Laurie Richards, Colorado State University
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- Book:
- Natural Resource Management Reimagined
- Published online:
- 25 February 2021
- Print publication:
- 11 March 2021, pp 90-130
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Summary
Ecosystem modeling, a pillar of the systems ecology paradigm (SEP), addresses questions such as, how much carbon and nitrogen are cycled within ecological sites, landscapes, or indeed the earth system? Or how are human activities modifying these flows? Modeling, when coupled with field and laboratory studies, represents the essence of the SEP in that they embody accumulated knowledge and generate hypotheses to test understanding of ecosystem processes and behavior. Initially, ecosystem models were primarily used to improve our understanding about how biophysical aspects of ecosystems operate. However, current ecosystem models are widely used to make accurate predictions about how large-scale phenomena such as climate change and management practices impact ecosystem dynamics and assess potential effects of these changes on economic activity and policy making. In sum, ecosystem models embedded in the SEP remain our best mechanism to integrate diverse types of knowledge regarding how the earth system functions and to make quantitative predictions that can be confronted with observations of reality. Modeling efforts discussed are the Century ecosystem model, DayCent ecosystem model, Grassland Ecosystem Model ELM, food web models, Savanna model, agent-based and coupled systems modeling, and Bayesian modeling.
7 - Evolution of the Systems Ecology Paradigm in Managing Ecosystems
- Edited by Robert G. Woodmansee, Colorado State University, John C. Moore, Colorado State University, Dennis S. Ojima, Colorado State University, Laurie Richards, Colorado State University
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- Book:
- Natural Resource Management Reimagined
- Published online:
- 25 February 2021
- Print publication:
- 11 March 2021, pp 202-244
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Summary
The systems ecology paradigm (SEP) emerged in the late 1960s at a time when societies throughout the world were beginning to recognize that our environment and natural resources were being threatened by their activities. Management practices in rangelands, forests, agricultural lands, wetlands, and waterways were inadequate to meet the challenges of deteriorating environments, many of which were caused by the practices themselves. Scientists recognized an immediate need was developing a knowledge base about how ecosystems function. That effort took nearly two decades (1980s) and concluded with the acceptance that humans were components of ecosystems, not just controllers and manipulators of lands and waters. While ecosystem science was being developed, management options based on ecosystem science were shifting dramatically toward practices supporting sustainability, resilience, ecosystem services, biodiversity, and local to global interconnections of ecosystems. Emerging from the new knowledge about how ecosystems function and the application of the systems ecology approach was the collaboration of scientists, managers, decision-makers, and stakeholders locally and globally. Today’s concepts of ecosystem management and related ideas, such as sustainable agriculture, ecosystem health and restoration, consequences of and adaptation to climate change, and many other important local to global challenges are a direct result of the SEP.
6 - Emergence of Cross-Scale Structural and Functional Processes in Ecosystem Science
- Edited by Robert G. Woodmansee, Colorado State University, John C. Moore, Colorado State University, Dennis S. Ojima, Colorado State University, Laurie Richards, Colorado State University
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- Book:
- Natural Resource Management Reimagined
- Published online:
- 25 February 2021
- Print publication:
- 11 March 2021, pp 140-201
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Summary
Fundamental knowledge about the processes that control the functioning of the biophysical workings of ecosystems has expanded exponentially since the late 1960s. Scientists, then, had only primitive knowledge about C, N, P, S, and H2O cycles; plant, animal, and soil microbialinteractions and dynamics; and land, atmosphere, and water interactions. With the advent of systems ecology paradigm (SEP) and the explosion of technologies supporting field and laboratory research, scientists throughout the world were able to assemble the knowledge base known today as ecosystem science. This chapter describes, through the eyes of scientists associated with the Natural Resource Ecology Laboratory (NREL) at Colorado State University (CSU), the evolution of the SEP in discovering how biophysical systems at small scales (ecological sites, landscapes) function as systems. The NREL and CSU are epicenters of the development of ecosystem science. Later, that knowledge, including humans as components of ecosystems, has been applied to small regions, regions, and the globe. Many research results that have formed the foundation for ecosystem science and management of natural resources, terrestrial environments, and its waters are described in this chapter. Throughout are direct and implicit references to the vital collaborations with the global network of ecosystem scientists.
8 - Land/Atmosphere/Water Interactions
- Edited by Robert G. Woodmansee, Colorado State University, John C. Moore, Colorado State University, Dennis S. Ojima, Colorado State University, Laurie Richards, Colorado State University
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- Book:
- Natural Resource Management Reimagined
- Published online:
- 25 February 2021
- Print publication:
- 11 March 2021, pp 245-278
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Summary
Emerging from the warehouse of knowledge about terrestrial ecosystem functioning and the application of the systems ecology paradigm, exemplified by the power of simulation modeling, tremendous strides have been made linking the interactions of the land, atmosphere, and water locally to globally. Through integration of ecosystem, atmospheric, soil, and more recently social science interactions, plausible scenarios and even reasonable predictions are now possible about the outcomes of human activities. The applications of that knowledge to the effects of changing climates, human-caused nitrogen enrichment of ecosystems, and altered UV-B radiation represent challenges addressed in this chapter. The primary linkages addressed are through the C, N, S, and H2O cycles, and UV-B radiation. Carbon dioxide exchanges between land and the atmosphere, N additions and losses to and from lands and waters, early studies of SO2 in grassland ecosystem, and the effects of UV-B radiation on ecosystems have been mainstays of research described in this chapter. This research knowledge has been used in international and national climate assessments, for example the IPCC, US National Climate Assessment, and Paris Climate Accord. Likewise, the knowledge has been used to develop concepts and technologies related to sustainable agriculture, C sequestration, and food security.