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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.
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.
The Evolutionary Map of the Universe Pilot Survey – ADDENDUM
- Ray P. Norris, Joshua Marvil, J. D. Collier, Anna D. Kapińska, Andrew N. O’Brien, L. Rudnick, Heinz Andernach, Jacobo Asorey, Michael J. I. Brown, Marcus Brüggen, Evan Crawford, Jayanne English, Syed Faisal ur Rahman, Miroslav D. Filipović, Yjan Gordon, Gülay Gürkan, Catherine Hale, Andrew M. Hopkins, Minh T. Huynh, Kim HyeongHan, M. James Jee, Bärbel S. Koribalski, Emil Lenc, Kieran Luken, David Parkinson, Isabella Prandoni, Wasim Raja, Thomas H. Reiprich, Christopher J. Riseley, Stanislav S. Shabala, Jaimie R. Sheil, Tessa Vernstrom, Matthew T. Whiting, James R. Allison, C. S. Anderson, Lewis Ball, Martin Bell, John Bunton, T. J. Galvin, Neeraj Gupta, Aidan Hotan, Colin Jacka, Peter J. Macgregor, Elizabeth K. Mahony, Umberto Maio, Vanessa Moss, M. Pandey-Pommier, Maxim A. Voronkov
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- Publications of the Astronomical Society of Australia / Volume 39 / 2022
- Published online by Cambridge University Press:
- 02 November 2022, e055
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Neighbourhood-level social capital, marginalisation, and the incidence of schizophrenia and schizoaffective disorder in Toronto, Canada: a retrospective population-based cohort study
- Martin Rotenberg, Andrew Tuck, Kelly K. Anderson, Kwame McKenzie
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- Psychological Medicine / Volume 53 / Issue 6 / April 2023
- Published online by Cambridge University Press:
- 23 November 2021, pp. 2643-2651
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Background
Studies have shown mixed results regarding social capital and the risk of developing a psychotic disorder, and this has yet to be studied in North America. We sought to examine the relationship between neighbourhood-level marginalisation, social capital, and the incidence of schizophrenia and schizoaffective disorder in Toronto, Canada.
MethodsWe used a retrospective population-based cohort to identify incident cases of schizophrenia and schizoaffective disorder over a 10 year period and accounted for neighbourhood-level marginalisation and a proxy indicator of neighbourhood social capital. Mixed Poisson regression models were used to estimate adjusted incidence rate ratios (aIRRs).
ResultsIn the cohort (n = 649 020) we identified 4841 incident cases of schizophrenia and schizoaffective disorder. A 27% variation in incidence was observed between neighbourhoods. All marginalisation dimensions, other than ethnic concentration, were associated with incidence. Compared to areas with low social capital, areas with intermediate social capital in the second [aIRR = 1.17, 95% confidence interval (CI) 1.03–1.33] and third (aIRR = 1.23, 95% CI 1.08–1.40) quintiles had elevated incidence rates after accounting for marginalisation. There was a higher risk associated with the intermediate levels of social capital (aIRR = 1.18, 95% CI 1.00–1.39) when analysed in only the females in the cohort, but the CI includes the possibility of a null effect.
ConclusionsThe risk of developing schizophrenia and schizoaffective disorder in Toronto varies by neighbourhood and is associated with socioenvironmental exposures. Social capital was not linearly associated with risk, and risk differs by sex and social capital quintile. Future research should examine these relationships with different forms of social capital and examine how known individual-level risk factors impact these findings.
Ten new insights in climate science 2021: a horizon scan
- Maria A. Martin, Olga Alcaraz Sendra, Ana Bastos, Nico Bauer, Christoph Bertram, Thorsten Blenckner, Kathryn Bowen, Paulo M. Brando, Tanya Brodie Rudolph, Milena Büchs, Mercedes Bustamante, Deliang Chen, Helen Cleugh, Purnamita Dasgupta, Fatima Denton, Jonathan F. Donges, Felix Kwabena Donkor, Hongbo Duan, Carlos M. Duarte, Kristie L. Ebi, Clea M. Edwards, Anja Engel, Eleanor Fisher, Sabine Fuss, Juliana Gaertner, Andrew Gettelman, Cécile A.J. Girardin, Nicholas R. Golledge, Jessica F. Green, Michael R. Grose, Masahiro Hashizume, Sophie Hebden, Helmke Hepach, Marina Hirota, Huang-Hsiung Hsu, Satoshi Kojima, Sharachchandra Lele, Sylvia Lorek, Heike K. Lotze, H. Damon Matthews, Darren McCauley, Desta Mebratu, Nadine Mengis, Rachael H. Nolan, Erik Pihl, Stefan Rahmstorf, Aaron Redman, Colleen E. Reid, Johan Rockström, Joeri Rogelj, Marielle Saunois, Lizzie Sayer, Peter Schlosser, Giles B. Sioen, Joachim H. Spangenberg, Detlef Stammer, Thomas N.S. Sterner, Nicola Stevens, Kirsten Thonicke, Hanqin Tian, Ricarda Winkelmann, James Woodcock
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- Journal:
- Global Sustainability / Volume 4 / 2021
- Published online by Cambridge University Press:
- 18 October 2021, e25
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Non-technical summary
We summarize some of the past year's most important findings within climate change-related research. New research has improved our understanding about the remaining options to achieve the Paris Agreement goals, through overcoming political barriers to carbon pricing, taking into account non-CO2 factors, a well-designed implementation of demand-side and nature-based solutions, resilience building of ecosystems and the recognition that climate change mitigation costs can be justified by benefits to the health of humans and nature alone. We consider new insights about what to expect if we fail to include a new dimension of fire extremes and the prospect of cascading climate tipping elements.
Technical summaryA synthesis is made of 10 topics within climate research, where there have been significant advances since January 2020. The insights are based on input from an international open call with broad disciplinary scope. Findings include: (1) the options to still keep global warming below 1.5 °C; (2) the impact of non-CO2 factors in global warming; (3) a new dimension of fire extremes forced by climate change; (4) the increasing pressure on interconnected climate tipping elements; (5) the dimensions of climate justice; (6) political challenges impeding the effectiveness of carbon pricing; (7) demand-side solutions as vehicles of climate mitigation; (8) the potentials and caveats of nature-based solutions; (9) how building resilience of marine ecosystems is possible; and (10) that the costs of climate change mitigation policies can be more than justified by the benefits to the health of humans and nature.
Social media summaryHow do we limit global warming to 1.5 °C and why is it crucial? See highlights of latest climate science.
The ASKAP Variables and Slow Transients (VAST) Pilot Survey
- Part of
- Tara Murphy, David L. Kaplan, Adam J. Stewart, Andrew O’Brien, Emil Lenc, Sergio Pintaldi, Joshua Pritchard, Dougal Dobie, Archibald Fox, James K. Leung, Tao An, Martin E. Bell, Jess W. Broderick, Shami Chatterjee, Shi Dai, Daniele d’Antonio, Gerry Doyle, B. M. Gaensler, George Heald, Assaf Horesh, Megan L. Jones, David McConnell, Vanessa A. Moss, Wasim Raja, Gavin Ramsay, Stuart Ryder, Elaine M. Sadler, Gregory R. Sivakoff, Yuanming Wang, Ziteng Wang, Michael S. Wheatland, Matthew Whiting, James R. Allison, C. S. Anderson, Lewis Ball, K. Bannister, D. C.-J. Bock, R. Bolton, J. D. Bunton, R. Chekkala, A. P Chippendale, F. R. Cooray, N. Gupta, D. B. Hayman, K. Jeganathan, B. Koribalski, K. Lee-Waddell, Elizabeth K. Mahony, J. Marvil, N. M. McClure-Griffiths, P. Mirtschin, A. Ng, S. Pearce, C. Phillips, M. A. Voronkov
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- Journal:
- Publications of the Astronomical Society of Australia / Volume 38 / 2021
- Published online by Cambridge University Press:
- 12 October 2021, e054
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The Variables and Slow Transients Survey (VAST) on the Australian Square Kilometre Array Pathfinder (ASKAP) is designed to detect highly variable and transient radio sources on timescales from 5 s to $\sim\!5$ yr. In this paper, we present the survey description, observation strategy and initial results from the VAST Phase I Pilot Survey. This pilot survey consists of $\sim\!162$ h of observations conducted at a central frequency of 888 MHz between 2019 August and 2020 August, with a typical rms sensitivity of $0.24\ \mathrm{mJy\ beam}^{-1}$ and angular resolution of $12-20$ arcseconds. There are 113 fields, each of which was observed for 12 min integration time, with between 5 and 13 repeats, with cadences between 1 day and 8 months. The total area of the pilot survey footprint is 5 131 square degrees, covering six distinct regions of the sky. An initial search of two of these regions, totalling 1 646 square degrees, revealed 28 highly variable and/or transient sources. Seven of these are known pulsars, including the millisecond pulsar J2039–5617. Another seven are stars, four of which have no previously reported radio detection (SCR J0533–4257, LEHPM 2-783, UCAC3 89–412162 and 2MASS J22414436–6119311). Of the remaining 14 sources, two are active galactic nuclei, six are associated with galaxies and the other six have no multi-wavelength counterparts and are yet to be identified.
The Evolutionary Map of the Universe pilot survey
- Part of
- Ray P. Norris, Joshua Marvil, J. D. Collier, Anna D. Kapińska, Andrew N. O’Brien, L. Rudnick, Heinz Andernach, Jacobo Asorey, Michael J. I. Brown, Marcus Brüggen, Evan Crawford, Jayanne English, Syed Faisal ur Rahman, Miroslav D. Filipović, Yjan Gordon, Gülay Gürkan, Catherine Hale, Andrew M. Hopkins, Minh T. Huynh, Kim HyeongHan, M. James Jee, Bärbel S. Koribalski, Emil Lenc, Kieran Luken, David Parkinson, Isabella Prandoni, Wasim Raja, Thomas H. Reiprich, Christopher J. Riseley, Stanislav S. Shabala, Jaimie R. Sheil, Tessa Vernstrom, Matthew T. Whiting, James R. Allison, C. S. Anderson, Lewis Ball, Martin Bell, John Bunton, T. J. Galvin, Neeraj Gupta, Aidan Hotan, Colin Jacka, Peter J. Macgregor, Elizabeth K. Mahony, Umberto Maio, Vanessa Moss, M. Pandey-Pommier, Maxim A. Voronkov
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- Journal:
- Publications of the Astronomical Society of Australia / Volume 38 / 2021
- Published online by Cambridge University Press:
- 07 September 2021, e046
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We present the data and initial results from the first pilot survey of the Evolutionary Map of the Universe (EMU), observed at 944 MHz with the Australian Square Kilometre Array Pathfinder (ASKAP) telescope. The survey covers $270 \,\mathrm{deg}^2$ of an area covered by the Dark Energy Survey, reaching a depth of 25–30 $\mu\mathrm{Jy\ beam}^{-1}$ rms at a spatial resolution of $\sim$ 11–18 arcsec, resulting in a catalogue of $\sim$ 220 000 sources, of which $\sim$ 180 000 are single-component sources. Here we present the catalogue of single-component sources, together with (where available) optical and infrared cross-identifications, classifications, and redshifts. This survey explores a new region of parameter space compared to previous surveys. Specifically, the EMU Pilot Survey has a high density of sources, and also a high sensitivity to low surface brightness emission. These properties result in the detection of types of sources that were rarely seen in or absent from previous surveys. We present some of these new results here.
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.
Community-Driven Methods for Open and Reproducible Software Tools for Analyzing Datasets from Atom Probe Microscopy
- Markus Kühbach, Andrew J. London, Jing Wang, Daniel K. Schreiber, Francisca Mendez Martin, Iman Ghamarian, Huma Bilal, Anna V. Ceguerra
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- Journal:
- Microscopy and Microanalysis / Volume 28 / Issue 4 / August 2022
- Published online by Cambridge University Press:
- 27 July 2021, pp. 1038-1053
- Print publication:
- August 2022
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Atom probe tomography, and related methods, probe the composition and the three-dimensional architecture of materials. The software tools which microscopists use, and how these tools are connected into workflows, make a substantial contribution to the accuracy and precision of such material characterization experiments. Typically, we adapt methods from other communities like mathematics, data science, computational geometry, artificial intelligence, or scientific computing. We also realize that improving on research data management is a challenge when it comes to align with the FAIR data stewardship principles. Faced with this global challenge, we are convinced it is useful to join forces. Here, we report the results and challenges with an inter-laboratory call for developing test cases for several types of atom probe microscopy software tools. The results support why defining detailed recipes of software workflows and sharing these recipes is necessary and rewarding: Open source tools and (meta)data exchange can help to make our day-to-day data processing tasks become more efficient, the training of new users and knowledge transfer become easier, and assist us with automated quantification of uncertainties to gain access to substantiated results.
The Rapid ASKAP Continuum Survey I: Design and first results
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- D. McConnell, C. L. Hale, E. Lenc, J. K. Banfield, George Heald, A. W. Hotan, James K. Leung, Vanessa A. Moss, Tara Murphy, Andrew O’Brien, Joshua Pritchard, Wasim Raja, Elaine M. Sadler, Adam Stewart, Alec J. M. Thomson, M. Whiting, James R. Allison, S. W. Amy, C. Anderson, Lewis Ball, Keith W. Bannister, Martin Bell, Douglas C.-J. Bock, Russ Bolton, J. D. Bunton, A. P. Chippendale, J. D. Collier, F. R. Cooray, T. J. Cornwell, P. J. Diamond, P. G. Edwards, N. Gupta, Douglas B. Hayman, Ian Heywood, C. A. Jackson, Bärbel S. Koribalski, Karen Lee-Waddell, N. M. McClure-Griffiths, Alan Ng, Ray P. Norris, Chris Phillips, John E. Reynolds, Daniel N. Roxby, Antony E. T. Schinckel, Matt Shields, Chenoa Tremblay, A. Tzioumis, M. A. Voronkov, Tobias Westmeier
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- Publications of the Astronomical Society of Australia / Volume 37 / 2020
- Published online by Cambridge University Press:
- 30 November 2020, e048
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The Rapid ASKAP Continuum Survey (RACS) is the first large-area survey to be conducted with the full 36-antenna Australian Square Kilometre Array Pathfinder (ASKAP) telescope. RACS will provide a shallow model of the ASKAP sky that will aid the calibration of future deep ASKAP surveys. RACS will cover the whole sky visible from the ASKAP site in Western Australia and will cover the full ASKAP band of 700–1800 MHz. The RACS images are generally deeper than the existing NRAO VLA Sky Survey and Sydney University Molonglo Sky Survey radio surveys and have better spatial resolution. All RACS survey products will be public, including radio images (with $\sim$ 15 arcsec resolution) and catalogues of about three million source components with spectral index and polarisation information. In this paper, we present a description of the RACS survey and the first data release of 903 images covering the sky south of declination $+41^\circ$ made over a 288-MHz band centred at 887.5 MHz.
Recreating the OSIRIS-REx slingshot manoeuvre from a network of ground-based sensors
- Trent Jansen-Sturgeon, Benjamin A. D. Hartig, Gregory J. Madsen, Philip A. Bland, Eleanor K. Sansom, Hadrien A. R. Devillepoix, Robert M. Howie, Martin Cupák, Martin C. Towner, Morgan A. Cox, Nicole D. Nevill, Zacchary N. P. Hoskins, Geoffrey P. Bonning, Josh Calcino, Jake T. Clark, Bryce M. Henson, Andrew Langendam, Samuel J. Matthews, Terence P. McClafferty, Jennifer T. Mitchell, Craig J. O’Neill, Luke T. Smith, Alastair W. Tait
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- Journal:
- Publications of the Astronomical Society of Australia / Volume 37 / 2020
- Published online by Cambridge University Press:
- 27 November 2020, e049
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Optical tracking systems typically trade off between astrometric precision and field of view. In this work, we showcase a networked approach to optical tracking using very wide field-of-view imagers that have relatively low astrometric precision on the scheduled OSIRIS-REx slingshot manoeuvre around Earth on 22 Sep 2017. As part of a trajectory designed to get OSIRIS-REx to NEO 101955 Bennu, this flyby event was viewed from 13 remote sensors spread across Australia and New Zealand to promote triangulatable observations. Each observatory in this portable network was constructed to be as lightweight and portable as possible, with hardware based off the successful design of the Desert Fireball Network. Over a 4-h collection window, we gathered 15 439 images of the night sky in the predicted direction of the OSIRIS-REx spacecraft. Using a specially developed streak detection and orbit determination data pipeline, we detected 2 090 line-of-sight observations. Our fitted orbit was determined to be within about 10 km of orbital telemetry along the observed 109 262 km length of OSIRIS-REx trajectory, and thus demonstrating the impressive capability of a networked approach to Space Surveillance and Tracking.
Optimism and risk of incident hypertension: a target for primordial prevention
- Laura D. Kubzansky, Julia K. Boehm, Andrew R. Allen, Loryana L. Vie, Tiffany E. Ho, Claudia Trudel-Fitzgerald, Hayami K. Koga, Lawrence M. Scheier, Martin E. P. Seligman
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- Journal:
- Epidemiology and Psychiatric Sciences / Volume 29 / 2020
- Published online by Cambridge University Press:
- 14 August 2020, e157
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Aims
Optimism is associated with reduced cardiovascular disease risk; however, few prospective studies have considered optimism in relation to hypertension risk specifically. We investigated whether optimism was associated with a lower risk of developing hypertension in U.S. service members, who are more likely to develop high blood pressure early in life. We also evaluated race/ethnicity, sex and age as potential effect modifiers of these associations.
MethodsParticipants were 103 486 hypertension-free U.S. Army active-duty soldiers (mean age 28.96 years, 61.76% White, 20.04% Black, 11.01% Hispanic, 4.09% Asian, and 3.10% others). We assessed optimism, sociodemographic characteristics, health conditions, health behaviours and depression status at baseline (2009–2010) via self-report and administrative records, and ascertained incident hypertension over follow-up (2010–2014) from electronic health records and health assessments. We used Cox proportional hazards regression models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs), and adjusted models for a broad range of relevant covariates.
ResultsOver a mean follow-up of 3.51 years, 15 052 incident hypertension cases occurred. The highest v. lowest optimism levels were associated with a 22% reduced risk of developing hypertension, after adjusting for all covariates including baseline blood pressure (HR = 0.78; 95% CI = 0.74–0.83). The difference in hypertension risk between the highest v. lowest optimism was also maintained when we excluded soldiers with hypertension in the first two years of follow-up and, separately, when we excluded soldiers with prehypertension at baseline. A dose–response relationship was evident with higher optimism associated with a lower relative risk (p < 0.001). Higher optimism was consistently associated with a lower risk of developing hypertension across sex, age and most race/ethnicity categories.
ConclusionsIn a diverse cohort of initially healthy male and female service members particularly vulnerable to developing hypertension, higher optimism levels were associated with reduced hypertension risk independently of sociodemographic and health factors, a particularly notable finding given the young and healthy population. Results suggest optimism is a health asset and a potential target for public health interventions.
Polygenic contributions to alcohol use and alcohol use disorders across population-based and clinically ascertained samples
- Emma C. Johnson, Sandra Sanchez-Roige, Laura Acion, Mark J. Adams, Kathleen K. Bucholz, Grace Chan, Michael J. Chao, David B. Chorlian, Danielle M. Dick, Howard J. Edenberg, Tatiana Foroud, Caroline Hayward, Jon Heron, Victor Hesselbrock, Matthew Hickman, Kenneth S. Kendler, Sivan Kinreich, John Kramer, Sally I-Chun Kuo, Samuel Kuperman, Dongbing Lai, Andrew M. McIntosh, Jacquelyn L. Meyers, Martin H. Plawecki, Bernice Porjesz, David Porteous, Marc A. Schuckit, Jinni Su, Yong Zang, Abraham A. Palmer, Arpana Agrawal, Toni-Kim Clarke, Alexis C. Edwards
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- Psychological Medicine / Volume 51 / Issue 7 / May 2021
- Published online by Cambridge University Press:
- 20 January 2020, pp. 1147-1156
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Background
Studies suggest that alcohol consumption and alcohol use disorders have distinct genetic backgrounds.
MethodsWe examined whether polygenic risk scores (PRS) for consumption and problem subscales of the Alcohol Use Disorders Identification Test (AUDIT-C, AUDIT-P) in the UK Biobank (UKB; N = 121 630) correlate with alcohol outcomes in four independent samples: an ascertained cohort, the Collaborative Study on the Genetics of Alcoholism (COGA; N = 6850), and population-based cohorts: Avon Longitudinal Study of Parents and Children (ALSPAC; N = 5911), Generation Scotland (GS; N = 17 461), and an independent subset of UKB (N = 245 947). Regression models and survival analyses tested whether the PRS were associated with the alcohol-related outcomes.
ResultsIn COGA, AUDIT-P PRS was associated with alcohol dependence, AUD symptom count, maximum drinks (R2 = 0.47–0.68%, p = 2.0 × 10−8–1.0 × 10−10), and increased likelihood of onset of alcohol dependence (hazard ratio = 1.15, p = 4.7 × 10−8); AUDIT-C PRS was not an independent predictor of any phenotype. In ALSPAC, the AUDIT-C PRS was associated with alcohol dependence (R2 = 0.96%, p = 4.8 × 10−6). In GS, AUDIT-C PRS was a better predictor of weekly alcohol use (R2 = 0.27%, p = 5.5 × 10−11), while AUDIT-P PRS was more associated with problem drinking (R2 = 0.40%, p = 9.0 × 10−7). Lastly, AUDIT-P PRS was associated with ICD-based alcohol-related disorders in the UKB subset (R2 = 0.18%, p < 2.0 × 10−16).
ConclusionsAUDIT-P PRS was associated with a range of alcohol-related phenotypes across population-based and ascertained cohorts, while AUDIT-C PRS showed less utility in the ascertained cohort. We show that AUDIT-P is genetically correlated with both use and misuse and demonstrate the influence of ascertainment schemes on PRS analyses.
2083: What factors explain failure to meet clinical recommendations for preschool children’s screen-time?
- Amanda E. Staiano, Andrew T. Allen, E. Kipling Webster, Corby K. Martin
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- Journal:
- Journal of Clinical and Translational Science / Volume 1 / Issue S1 / September 2017
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- 10 May 2018, pp. 39-40
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OBJECTIVES/SPECIFIC AIMS: The American Academy of Pediatrics (AAP) recommends that preschool-aged children spend no more than 2 hours/day using digital screens such as TVs. However, there is a proliferation of digital screens in children’s daily lives both at school and at home. The purpose of this study was to examine factors that contribute to children’s screen-time, including their demographic characteristics and whether or not they have screen-time at school. METHODS/STUDY POPULATION: In total, 59 children (3.3±0.4 years of age; 47% female) enrolled in 3 child care centers participated. Center directors reported school screen-time; 1 center was classified as not providing screen-time and 2 centers were classified as providing screen-time. Parents reported child’s age, sex, and maternal education as a proxy for socio-economic status. Parents reported child’s out-of-school screen-time by responding to the question “During the past 30 days, on average how many hours per day did your child sit and watch TV or videos outside of school?” Additional questions queried how many hours per day did the child “use a computer or play computer games,” “play video games,” “use a smartphone,” and “use an iPad or tablet.” Children’s height and weight were collected using standard clinic procedures and body mass index (BMI) was calculated. T tests were used to examine differences in screen-time by age, sex, and school screen-time. General linear models were used to examine the influence of school screen-time (1=no screen-time, 0=between 1 and 60 min/day of screen-time), age, BMI, and maternal education on out-of-school screen-time and time spent with each device. Logistic regression analysis was used to examine likelihood of meeting screen-time recommendations based on the same characteristics. RESULTS/ANTICIPATED RESULTS: Parent-reported total screen-time was 6.3±3.6 hours/day (h/d); specifically, 2.5±1.1 h/d watching TV, 1.5±2.2 h/d using a smartphone, 1.1±0.9 h/d using a tablet, 0.8±1.0 h/d on a computer, and 0.5±0.7 h/d playing video games. Based on total screen-time, 15% of children met AAP recommendations; based on TV viewing only, 52% met AAP recommendations. The 4-year-old children viewed more screen-time overall compared to the 3-year-old children including on TV, computer, and tablet (p<0.05), but there were no sex differences. In fully adjusted linear models, out-of-school screen-time was lower among those who had no screen-time at school (p=0.02) and higher among older children (p<0.01). Computer use was higher among older children (p=0.02). Older children and those with lower maternal education were less likely to meet clinical recommendations based on TV viewing (p<0.05). There were no observed associations with likelihood of meeting clinical recommendations based on total screen-time. BMI was not a significant predictor of screen-time. DISCUSSION/SIGNIFICANCE OF IMPACT: The majority of children exceeded AAP screen-time limits, with screen-time sharply higher among older children, and the associations did not vary by weight status. Children who attended schools that allowed screen-time had higher amounts of out-of-school screen-time. Pediatricians and healthcare providers should query parents on children’s screen-time practices at home and at school and offer strategies to help families meet the clinical recommendations.
Patient Cessation Activity after Automatic Referral to a Dedicated Cessation Support Service
- Katharine A. Amato, Mary E. Reid, Maansi Bansal-Travers, Heather M. Ochs-Balcom, K. Michael Cummings, Martin Mahoney, James Marshall, Andrew Hyland
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- Journal:
- Journal of Smoking Cessation / Volume 13 / Issue 2 / June 2018
- Published online by Cambridge University Press:
- 18 May 2017, pp. 78-86
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- June 2018
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Introduction: We characterised tobacco use, cessation patterns, and patient satisfaction with a cessation support program at an NCI Designated Comprehensive Cancer Center following a mandatory tobacco assessment and automatic referral.
Methods: A 3-month follow-up survey (via web, paper, or telephone) was administered between March 2013 and November 2013 for all patients referred to and contacted by a cessation support service, and who consented to participation three months prior to administration. Patients were asked about their perceived importance and self-efficacy to quit smoking, quit attempts, and satisfaction with the cessation service.
Results: Fifty-two percent (257/499) of patients who participated in the cessation support service, and consented to be contacted again, completed a follow-up survey. Of those who participated, 9.7% were referred to the service as having recently quit tobacco (in the past 30 days) and 23.6% reported having quit at the time of first contact. At the 3-month follow-up, 48.1% reported being smoke-free for the previous seven days. When patients were asked about their experience with the cessation service, 86.4% reported being very or mostly satisfied with the service, and 64.3% reported that their experience with the service increased their satisfaction with the care received at the cancer centre.
Conclusions: Our findings suggest that recently diagnosed cancer patients are aware that quitting tobacco is important, are making attempts to quit, and are amenable to an opt-out automatic referral cessation support service as part of their cancer care.
Low-Frequency Spectral Energy Distributions of Radio Pulsars Detected with the Murchison Widefield Array
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- Tara Murphy, David L. Kaplan, Martin E. Bell, J. R. Callingham, Steve Croft, Simon Johnston, Dougal Dobie, Andrew Zic, Jake Hughes, Christene Lynch, Paul Hancock, Natasha Hurley-Walker, Emil Lenc, K. S. Dwarakanath, B.-Q. For, B. M. Gaensler, L. Hindson, M. Johnston-Hollitt, A. D. Kapińska, B. McKinley, J. Morgan, A. R. Offringa, P. Procopio, L. Staveley-Smith, R. Wayth, C. Wu, Q. Zheng
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- Publications of the Astronomical Society of Australia / Volume 34 / 2017
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- 26 April 2017, e020
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We present low-frequency spectral energy distributions of 60 known radio pulsars observed with the Murchison Widefield Array telescope. We searched the GaLactic and Extragalactic All-sky Murchison Widefield Array survey images for 200-MHz continuum radio emission at the position of all pulsars in the Australia Telescope National Facility (ATNF) pulsar catalogue. For the 60 confirmed detections, we have measured flux densities in 20 × 8 MHz bands between 72 and 231 MHz. We compare our results to existing measurements and show that the Murchison Widefield Array flux densities are in good agreement.
Multibeam bathymetric and sediment profiler evidence for ice grounding on the Chukchi Borderland, Arctic Ocean
- Martin Jakobsson, James V. Gardner, Peter R. Vogt, Larry A. Mayer, Andrew Armstrong, Jan Backman, Rick Brennan, Brian Calder, John K. Hall, Barbara Kraft
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- Quaternary Research / Volume 63 / Issue 2 / March 2005
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- 20 January 2017, pp. 150-160
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Multibeam bathymetry and 3.5-kHz sub-bottom profiler data collected from the US icebreaker Healy in 2003 provide convincing evidence for grounded ice on the Chukchi Borderland off the northern Alaskan margin, Arctic Ocean. The data show parallel, glacially induced seafloor scours, or grooves, and intervening ridges that reach widths of 1000 m (rim to rim) and as much as 40 m relief. Following previous authors, we refer to these features as “megascale glacial lineations (MSGLs).” Additional support for ice grounding is apparent from stratigraphic unconformities, interpreted to have been caused by ice-induced erosion. Most likely, the observed sea-floor features represent evidence for massive ice-shelf grounding. The general ESE/WNW direction of the MSGLs, together with sediment, evidently bulldozed off the Chukchi Plateau, that is mapped on the western (Siberian) side of the plateau, suggests ice flow from the Canada Basin side of Chukchi Borderland. Two separate generations of glacially derived MSGLs are identified on the Chukchi Borderland from the Healy geophysical data. The deepest and oldest extensive MSGLs appear to be draped by sediments less than 5 m thick, whereas no sediment drape can be distinguished within the resolution of the sub-bottom profiles on the younger generation.
Personality Polygenes, Positive Affect, and Life Satisfaction
- Alexander Weiss, Bart M. L. Baselmans, Edith Hofer, Jingyun Yang, Aysu Okbay, Penelope A. Lind, Mike B. Miller, Ilja M. Nolte, Wei Zhao, Saskia P. Hagenaars, Jouke-Jan Hottenga, Lindsay K. Matteson, Harold Snieder, Jessica D. Faul, Catharina A. Hartman, Patricia A. Boyle, Henning Tiemeier, Miriam A. Mosing, Alison Pattie, Gail Davies, David C. Liewald, Reinhold Schmidt, Philip L. De Jager, Andrew C. Heath, Markus Jokela, John M. Starr, Albertine J. Oldehinkel, Magnus Johannesson, David Cesarini, Albert Hofman, Sarah E. Harris, Jennifer A. Smith, Liisa Keltikangas-Järvinen, Laura Pulkki-Råback, Helena Schmidt, Jacqui Smith, William G. Iacono, Matt McGue, David A. Bennett, Nancy L. Pedersen, Patrik K. E. Magnusson, Ian J. Deary, Nicholas G. Martin, Dorret I. Boomsma, Meike Bartels, Michelle Luciano
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- Twin Research and Human Genetics / Volume 19 / Issue 5 / October 2016
- Published online by Cambridge University Press:
- 22 August 2016, pp. 407-417
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Approximately half of the variation in wellbeing measures overlaps with variation in personality traits. Studies of non-human primate pedigrees and human twins suggest that this is due to common genetic influences. We tested whether personality polygenic scores for the NEO Five-Factor Inventory (NEO-FFI) domains and for item response theory (IRT) derived extraversion and neuroticism scores predict variance in wellbeing measures. Polygenic scores were based on published genome-wide association (GWA) results in over 17,000 individuals for the NEO-FFI and in over 63,000 for the IRT extraversion and neuroticism traits. The NEO-FFI polygenic scores were used to predict life satisfaction in 7 cohorts, positive affect in 12 cohorts, and general wellbeing in 1 cohort (maximal N = 46,508). Meta-analysis of these results showed no significant association between NEO-FFI personality polygenic scores and the wellbeing measures. IRT extraversion and neuroticism polygenic scores were used to predict life satisfaction and positive affect in almost 37,000 individuals from UK Biobank. Significant positive associations (effect sizes <0.05%) were observed between the extraversion polygenic score and wellbeing measures, and a negative association was observed between the polygenic neuroticism score and life satisfaction. Furthermore, using GWA data, genetic correlations of -0.49 and -0.55 were estimated between neuroticism with life satisfaction and positive affect, respectively. The moderate genetic correlation between neuroticism and wellbeing is in line with twin research showing that genetic influences on wellbeing are also shared with other independent personality domains.
From alcohol initiation to tolerance to problems: Discordant twin modeling of a developmental process
- Arielle R. Deutsch, Wendy S. Slutske, Michael T. Lynskey, Kathleen K. Bucholz, Pamela A. F. Madden, Andrew C. Heath, Nicholas G. Martin
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- Development and Psychopathology / Volume 29 / Issue 3 / August 2017
- Published online by Cambridge University Press:
- 15 July 2016, pp. 845-861
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The current study examined a stage-based alcohol use trajectory model to test for potential causal effects of earlier drinking milestones on later drinking milestones in a combined sample of two cohorts of Australian monozygotic and same-sex dizygotic twins (N = 7,398, age M = 30.46, SD = 2.61, 61% male, 56% monozygotic twins). Ages of drinking, drunkenness, regular drinking, tolerance, first nontolerance alcohol use disorder symptom, and alcohol use disorder symptom onsets were assessed retrospectively. Ages of milestone attainment (i.e., age-of-onset) and time between milestones (i.e., time-to-event) were examined via frailty models within a multilevel discordant twin design. For age-of-onset models, earlier ages of onset of antecedent drinking milestones increased hazards for earlier ages of onset for more proximal subsequent drinking milestones. For the time-to-event models, however, earlier ages of onset for the “starting” milestone decreased risk for a shorter time period between the starting and the “ending” milestone. Earlier age of onset of intermediate milestones between starting and ending drinking milestones had the opposite effect, increasing risk for a shorter time period between the starting and ending milestones. These results are consistent with a causal effect of an earlier age of drinking milestone onset on temporally proximal subsequent drinking milestones.