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Personality Change in a Trial of Psilocybin Therapy vs Escitalopram Treatment for Depression – CORRIGENDUM
- Brandon Weiss, Induni Ginige, Lu Shannon, Bruna Giribaldi, Ashleigh Murphy-Beiner, Roberta Murphy, Michelle Baker-Jones, Jonny Martell, David J. Nutt, Robin L. Carhart-Harris, David Erritzoe
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- Journal:
- Psychological Medicine / Volume 54 / Issue 1 / January 2024
- Published online by Cambridge University Press:
- 19 July 2023, p. 217
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Personality change in a trial of psilocybin therapy v. escitalopram treatment for depression
- Brandon Weiss, Induni Ginige, Lu Shannon, Bruna Giribaldi, Ashleigh Murphy-Beiner, Roberta Murphy, Michelle Baker-Jones, Jonny Martell, David J. Nutt, Robin L. Carhart-Harris, David Erritzoe
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- Psychological Medicine / Volume 54 / Issue 1 / January 2024
- Published online by Cambridge University Press:
- 02 June 2023, pp. 178-192
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Background
Psilocybin Therapy (PT) is being increasingly studied as a psychiatric intervention. Personality relates to mental health and can be used to probe the nature of PT's therapeutic action.
MethodsIn a phase 2, double-blind, randomized, active comparator controlled trial involving patients with moderate-to-severe major depressive disorder, we compared psilocybin with escitalopram, over a core 6-week trial period. Five-Factor model personality domains, Big Five Aspect Scale Openness aspects, Absorption, and Impulsivity were measured at Baseline, Week 6, and Month 6 follow-up.
ResultsPT was associated with decreases in neuroticism (B = −0.63), introversion (B = −0.38), disagreeableness (B = −0.47), impulsivity (B = −0.40), and increases in absorption (B = 0.32), conscientiousness (B = 0.30), and openness (B = 0.23) at week 6, with neuroticism (B = −0.47) and disagreeableness (B = −0.41) remaining decreased at month 6. Escitalopram Treatment (ET) was associated with decreases in neuroticism (B = −0.38), disagreeableness (B = −0.26), impulsivity (B = −0.35), and increases in openness (B = 0.28) at week 6, with neuroticism (B = −0.46) remaining decreased at month 6. No significant between-condition differences were observed.
ConclusionsPersonality changes across both conditions were in a direction consistent with improved mental health. With the possible exception of trait absorption, there were no compelling between-condition differences warranting conclusions regarding a selective action of PT (v. ET) on personality; however, post-ET changes in personality were significantly moderated by pre-trial positive expectancy for escitalopram, whereas expectancy did not moderate response to PT.
Effect of lysergic acid diethylamide (LSD) on reinforcement learning in humans
- Jonathan W. Kanen, Qiang Luo, Mojtaba Rostami Kandroodi, Rudolf N. Cardinal, Trevor W. Robbins, David J. Nutt, Robin L. Carhart-Harris, Hanneke E. M. den Ouden
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- Journal:
- Psychological Medicine / Volume 53 / Issue 14 / October 2023
- Published online by Cambridge University Press:
- 22 November 2022, pp. 6434-6445
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Background
The non-selective serotonin 2A (5-HT2A) receptor agonist lysergic acid diethylamide (LSD) holds promise as a treatment for some psychiatric disorders. Psychedelic drugs such as LSD have been suggested to have therapeutic actions through their effects on learning. The behavioural effects of LSD in humans, however, remain incompletely understood. Here we examined how LSD affects probabilistic reversal learning (PRL) in healthy humans.
MethodsHealthy volunteers received intravenous LSD (75 μg in 10 mL saline) or placebo (10 mL saline) in a within-subjects design and completed a PRL task. Participants had to learn through trial and error which of three stimuli was rewarded most of the time, and these contingencies switched in a reversal phase. Computational models of reinforcement learning (RL) were fitted to the behavioural data to assess how LSD affected the updating (‘learning rates’) and deployment of value representations (‘reinforcement sensitivity’) during choice, as well as ‘stimulus stickiness’ (choice repetition irrespective of reinforcement history).
ResultsRaw data measures assessing sensitivity to immediate feedback (‘win-stay’ and ‘lose-shift’ probabilities) were unaffected, whereas LSD increased the impact of the strength of initial learning on perseveration. Computational modelling revealed that the most pronounced effect of LSD was the enhancement of the reward learning rate. The punishment learning rate was also elevated. Stimulus stickiness was decreased by LSD, reflecting heightened exploration. Reinforcement sensitivity differed by phase.
ConclusionsIncreased RL rates suggest LSD induced a state of heightened plasticity. These results indicate a potential mechanism through which revision of maladaptive associations could occur in the clinical application of LSD.
Effects of psilocybin versus escitalopram on rumination and thought suppression in depression
- Tommaso Barba, Sarah Buehler, Hannes Kettner, Caterina Radu, Bruna Giribaldi Cunha, David J. Nutt, David Erritzoe, Leor Roseman, Robin Carhart-Harris
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- Journal:
- BJPsych Open / Volume 8 / Issue 5 / September 2022
- Published online by Cambridge University Press:
- 06 September 2022, e163
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Background
Major depressive disorder is often associated with maladaptive coping strategies, including rumination and thought suppression.
AimsTo assess the comparative effect of the selective serotonin reuptake inhibitor escitalopram, and the serotonergic psychedelic psilocybin (COMP360), on rumination and thought suppression in major depressive disorder.
MethodBased on data derived from a randomised clinical trial (N = 59), we performed exploratory analyses on the impact of escitalopram versus psilocybin (i.e. condition) on rumination and thought suppression from 1 week before to 6 weeks after treatment inception (i.e. time), using mixed analysis of variance. Condition responder versus non-responder subgroup analyses were also done, using the standard definition of ≥50% symptom reduction.
ResultsA time×condition interaction was found for rumination (F(1, 56) = 4.58, P = 0.037) and thought suppression (F(1,57) = 5.88, P = 0.019), with post hoc tests revealing significant decreases exclusively in the psilocybin condition. When analysing via response, a significant time×condition×response interaction for thought suppression (F(1,54) = 8.42, P = 0.005) and a significant time×response interaction for rumination (F(1,54) = 23.50, P < 0.001) were evident. Follow-up tests revealed that decreased thought suppression was exclusive to psilocybin responders, whereas rumination decreased in both responder groups. In the psilocybin arm, decreases in rumination and thought suppression correlated with ego dissolution and session-linked psychological insight.
ConclusionsThese data provide further evidence on the therapeutic mechanisms of psilocybin and escitalopram in the treatment of depression.
Exploring the dynamics of flagellar dynein within the axoneme with Fluctuating Finite Element Analysis
- Robin A. Richardson, Benjamin S. Hanson, Daniel J. Read, Oliver G. Harlen, Sarah A. Harris
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- Quarterly Reviews of Biophysics / Volume 53 / 2020
- Published online by Cambridge University Press:
- 10 August 2020, e9
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Flagellar dyneins are the molecular motors responsible for producing the propagating bending motions of cilia and flagella. They are located within a densely packed and highly organised super-macromolecular cytoskeletal structure known as the axoneme. Using the mesoscale simulation technique Fluctuating Finite Element Analysis (FFEA), which represents proteins as viscoelastic continuum objects subject to explicit thermal noise, we have quantified the constraints on the range of molecular conformations that can be explored by dynein-c within the crowded architecture of the axoneme. We subsequently assess the influence of crowding on the 3D exploration of microtubule-binding sites, and specifically on the axial step length. Our calculations combine experimental information on the shape, flexibility and environment of dynein-c from three distinct sources; negative stain electron microscopy, cryo-electron microscopy (cryo-EM) and cryo-electron tomography (cryo-ET). Our FFEA simulations show that the super-macromolecular organisation of multiple protein complexes into higher-order structures can have a significant influence on the effective flexibility of the individual molecular components, and may, therefore, play an important role in the physical mechanisms underlying their biological function.
Stakeholder engagement in methodological research: Development of a clinical decision support tool
- Denise H. Daudelin, Robin Ruthazer, Manlik Kwong, Rebecca C. Lorenzana, Daniel J. Hannon, David M. Kent, Timothy E. McAlindon, Norma Terrin, John B. Wong, Harry P. Selker
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- Journal:
- Journal of Clinical and Translational Science / Volume 4 / Issue 2 / April 2020
- Published online by Cambridge University Press:
- 18 February 2020, pp. 133-140
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Introduction:
Shared patient–clinician decision-making is central to choosing between medical treatments. Decision support tools can have an important role to play in these decisions. We developed a decision support tool for deciding between nonsurgical treatment and surgical total knee replacement for patients with severe knee osteoarthritis. The tool aims to provide likely outcomes of alternative treatments based on predictive models using patient-specific characteristics. To make those models relevant to patients with knee osteoarthritis and their clinicians, we involved patients, family members, patient advocates, clinicians, and researchers as stakeholders in creating the models.
Methods:Stakeholders were recruited through local arthritis research, advocacy, and clinical organizations. After being provided with brief methodological education sessions, stakeholder views were solicited through quarterly patient or clinician stakeholder panel meetings and incorporated into all aspects of the project.
Results:Participating in each aspect of the research from determining the outcomes of interest to providing input on the design of the user interface displaying outcome predications, 86% (12/14) of stakeholders remained engaged throughout the project. Stakeholder engagement ensured that the prediction models that form the basis of the Knee Osteoarthritis Mathematical Equipoise Tool and its user interface were relevant for patient–clinician shared decision-making.
Conclusions:Methodological research has the opportunity to benefit from stakeholder engagement by ensuring that the perspectives of those most impacted by the results are involved in study design and conduct. While additional planning and investments in maintaining stakeholder knowledge and trust may be needed, they are offset by the valuable insights gained.
The use of patient-specific equipoise to support shared decision-making for clinical care and enrollment into clinical trials
- Harry P. Selker, Denise H. Daudelin, Robin Ruthazer, Manlik Kwong, Rebecca C. Lorenzana, Daniel J. Hannon, John B. Wong, David M. Kent, Norma Terrin, Alejandro D. Moreno-Koehler, Timothy E. McAlindon
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- Journal:
- Journal of Clinical and Translational Science / Volume 3 / Issue 1 / February 2019
- Published online by Cambridge University Press:
- 20 June 2019, pp. 27-36
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Background:
To enhance enrollment into randomized clinical trials (RCTs), we proposed electronic health record-based clinical decision support for patient–clinician shared decision-making about care and RCT enrollment, based on “mathematical equipoise.”
Objectives:As an example, we created the Knee Osteoarthritis Mathematical Equipoise Tool (KOMET) to determine the presence of patient-specific equipoise between treatments for the choice between total knee replacement (TKR) and nonsurgical treatment of advanced knee osteoarthritis.
Methods:With input from patients and clinicians about important pain and physical function treatment outcomes, we created a database from non-RCT sources of knee osteoarthritis outcomes. We then developed multivariable linear regression models that predict 1-year individual-patient knee pain and physical function outcomes for TKR and for nonsurgical treatment. These predictions allowed detecting mathematical equipoise between these two options for patients eligible for TKR. Decision support software was developed to graphically illustrate, for a given patient, the degree of overlap of pain and functional outcomes between the treatments and was pilot tested for usability, responsiveness, and as support for shared decision-making.
Results:The KOMET predictive regression model for knee pain had four patient-specific variables, and an r2 value of 0.32, and the model for physical functioning included six patient-specific variables, and an r2 of 0.34. These models were incorporated into prototype KOMET decision support software and pilot tested in clinics, and were generally well received.
Conclusions:Use of predictive models and mathematical equipoise may help discern patient-specific equipoise to support shared decision-making for selecting between alternative treatments and considering enrollment into an RCT.
An example of medical device-based projection of clinical trial enrollment: Use of electrocardiographic data to identify candidates for a trial in acute coronary syndromes
- Harry P. Selker, Manlik Kwong, Robin Ruthazer, Sheeona Gorman, Giuliana Green, Elizabeth Patchen, James E. Udelson, Howard A. Smithline, Michael R. Baumann, Paul A. Harris, Rashmee U. Shah, Sarah J. Nelson, Theodora Cohen, Elizabeth B. Jones, Brien A. Barnewolt, Andrew E. Williams
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- Journal of Clinical and Translational Science / Volume 2 / Issue 6 / December 2018
- Published online by Cambridge University Press:
- 14 May 2019, pp. 377-383
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Background:
To identify potential participants for clinical trials, electronic health records (EHRs) are searched at potential sites. As an alternative, we investigated using medical devices used for real-time diagnostic decisions for trial enrollment.
Methods:To project cohorts for a trial in acute coronary syndromes (ACS), we used electrocardiograph-based algorithms that identify ACS or ST elevation myocardial infarction (STEMI) that prompt clinicians to offer patients trial enrollment. We searched six hospitals’ electrocardiograph systems for electrocardiograms (ECGs) meeting the planned trial’s enrollment criterion: ECGs with STEMI or > 75% probability of ACS by the acute cardiac ischemia time-insensitive predictive instrument (ACI-TIPI). We revised the ACI-TIPI regression to require only data directly from the electrocardiograph, the e-ACI-TIPI using the same data used for the original ACI-TIPI (development set n = 3,453; test set n = 2,315). We also tested both on data from emergency department electrocardiographs from across the US (n = 8,556). We then used ACI-TIPI and e-ACI-TIPI to identify potential cohorts for the ACS trial and compared performance to cohorts from EHR data at the hospitals.
Results:Receiver-operating characteristic (ROC) curve areas on the test set were excellent, 0.89 for ACI-TIPI and 0.84 for the e-ACI-TIPI, as was calibration. On the national electrocardiographic database, ROC areas were 0.78 and 0.69, respectively, and with very good calibration. When tested for detection of patients with > 75% ACS probability, both electrocardiograph-based methods identified eligible patients well, and better than did EHRs.
Conclusion:Using data from medical devices such as electrocardiographs may provide accurate projections of available cohorts for clinical trials.
Education in Twins and Their Parents Across Birth Cohorts Over 100 years: An Individual-Level Pooled Analysis of 42-Twin Cohorts
- Karri Silventoinen, Aline Jelenkovic, Antti Latvala, Reijo Sund, Yoshie Yokoyama, Vilhelmina Ullemar, Catarina Almqvist, Catherine A. Derom, Robert F. Vlietinck, Ruth J. F. Loos, Christian Kandler, Chika Honda, Fujio Inui, Yoshinori Iwatani, Mikio Watanabe, Esther Rebato, Maria A. Stazi, Corrado Fagnani, Sonia Brescianini, Yoon-Mi Hur, Hoe-Uk Jeong, Tessa L. Cutler, John L. Hopper, Andreas Busjahn, Kimberly J. Saudino, Fuling Ji, Feng Ning, Zengchang Pang, Richard J. Rose, Markku Koskenvuo, Kauko Heikkilä, Wendy Cozen, Amie E. Hwang, Thomas M. Mack, Sisira H. Siribaddana, Matthew Hotopf, Athula Sumathipala, Fruhling Rijsdijk, Joohon Sung, Jina Kim, Jooyeon Lee, Sooji Lee, Tracy L. Nelson, Keith E. Whitfield, Qihua Tan, Dongfeng Zhang, Clare H. Llewellyn, Abigail Fisher, S. Alexandra Burt, Kelly L. Klump, Ariel Knafo-Noam, David Mankuta, Lior Abramson, Sarah E. Medland, Nicholas G. Martin, Grant W. Montgomery, Patrik K. E. Magnusson, Nancy L. Pedersen, Anna K. Dahl Aslan, Robin P. Corley, Brooke M. Huibregtse, Sevgi Y. Öncel, Fazil Aliev, Robert F. Krueger, Matt McGue, Shandell Pahlen, Gonneke Willemsen, Meike Bartels, Catharina E. M. van Beijsterveldt, Judy L. Silberg, Lindon J. Eaves, Hermine H. Maes, Jennifer R. Harris, Ingunn Brandt, Thomas S. Nilsen, Finn Rasmussen, Per Tynelius, Laura A. Baker, Catherine Tuvblad, Juan R. Ordoñana, Juan F. Sánchez-Romera, Lucia Colodro-Conde, Margaret Gatz, David A. Butler, Paul Lichtenstein, Jack H. Goldberg, K. Paige Harden, Elliot M. Tucker-Drob, Glen E. Duncan, Dedra Buchwald, Adam D. Tarnoki, David L. Tarnoki, Carol E. Franz, William S. Kremen, Michael J. Lyons, José A. Maia, Duarte L. Freitas, Eric Turkheimer, Thorkild I. A. Sørensen, Dorret I. Boomsma, Jaakko Kaprio
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- Twin Research and Human Genetics / Volume 20 / Issue 5 / October 2017
- Published online by Cambridge University Press:
- 04 October 2017, pp. 395-405
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Whether monozygotic (MZ) and dizygotic (DZ) twins differ from each other in a variety of phenotypes is important for genetic twin modeling and for inferences made from twin studies in general. We analyzed whether there were differences in individual, maternal and paternal education between MZ and DZ twins in a large pooled dataset. Information was gathered on individual education for 218,362 adult twins from 27 twin cohorts (53% females; 39% MZ twins), and on maternal and paternal education for 147,315 and 143,056 twins respectively, from 28 twin cohorts (52% females; 38% MZ twins). Together, we had information on individual or parental education from 42 twin cohorts representing 19 countries. The original education classifications were transformed to education years and analyzed using linear regression models. Overall, MZ males had 0.26 (95% CI [0.21, 0.31]) years and MZ females 0.17 (95% CI [0.12, 0.21]) years longer education than DZ twins. The zygosity difference became smaller in more recent birth cohorts for both males and females. Parental education was somewhat longer for fathers of DZ twins in cohorts born in 1990–1999 (0.16 years, 95% CI [0.08, 0.25]) and 2000 or later (0.11 years, 95% CI [0.00, 0.22]), compared with fathers of MZ twins. The results show that the years of both individual and parental education are largely similar in MZ and DZ twins. We suggest that the socio-economic differences between MZ and DZ twins are so small that inferences based upon genetic modeling of twin data are not affected.
Zygosity Differences in Height and Body Mass Index of Twins From Infancy to Old Age: A Study of the CODATwins Project
- Aline Jelenkovic, Yoshie Yokoyama, Reijo Sund, Chika Honda, Leonie H Bogl, Sari Aaltonen, Fuling Ji, Feng Ning, Zengchang Pang, Juan R. Ordoñana, Juan F. Sánchez-Romera, Lucia Colodro-Conde, S. Alexandra Burt, Kelly L. Klump, Sarah E. Medland, Grant W. Montgomery, Christian Kandler, Tom A. McAdams, Thalia C. Eley, Alice M. Gregory, Kimberly J. Saudino, Lise Dubois, Michel Boivin, Adam D. Tarnoki, David L. Tarnoki, Claire M. A. Haworth, Robert Plomin, Sevgi Y. Öncel, Fazil Aliev, Maria A. Stazi, Corrado Fagnani, Cristina D’Ippolito, Jeffrey M. Craig, Richard Saffery, Sisira H. Siribaddana, Matthew Hotopf, Athula Sumathipala, Fruhling Rijsdijk, Timothy Spector, Massimo Mangino, Genevieve Lachance, Margaret Gatz, David A. Butler, Gombojav Bayasgalan, Danshiitsoodol Narandalai, Duarte L Freitas, José Antonio Maia, K. Paige Harden, Elliot M. Tucker-Drob, Bia Kim, Youngsook Chong, Changhee Hong, Hyun Jung Shin, Kaare Christensen, Axel Skytthe, Kirsten O. Kyvik, Catherine A. Derom, Robert F. Vlietinck, Ruth J. F. Loos, Wendy Cozen, Amie E. Hwang, Thomas M. Mack, Mingguang He, Xiaohu Ding, Billy Chang, Judy L. Silberg, Lindon J. Eaves, Hermine H. Maes, Tessa L. Cutler, John L. Hopper, Kelly Aujard, Patrik K. E. Magnusson, Nancy L. Pedersen, Anna K. Dahl Aslan, Yun-Mi Song, Sarah Yang, Kayoung Lee, Laura A. Baker, Catherine Tuvblad, Morten Bjerregaard-Andersen, Henning Beck-Nielsen, Morten Sodemann, Kauko Heikkilä, Qihua Tan, Dongfeng Zhang, Gary E. Swan, Ruth Krasnow, Kerry L. Jang, Ariel Knafo-Noam, David Mankuta, Lior Abramson, Paul Lichtenstein, Robert F. Krueger, Matt McGue, Shandell Pahlen, Per Tynelius, Glen E. Duncan, Dedra Buchwald, Robin P. Corley, Brooke M. Huibregtse, Tracy L. Nelson, Keith E. Whitfield, Carol E. Franz, William S. Kremen, Michael J. Lyons, Syuichi Ooki, Ingunn Brandt, Thomas Sevenius Nilsen, Fujio Inui, Mikio Watanabe, Meike Bartels, Toos C. E. M. van Beijsterveldt, Jane Wardle, Clare H. Llewellyn, Abigail Fisher, Esther Rebato, Nicholas G. Martin, Yoshinori Iwatani, Kazuo Hayakawa, Joohon Sung, Jennifer R. Harris, Gonneke Willemsen, Andreas Busjahn, Jack H. Goldberg, Finn Rasmussen, Yoon-Mi Hur, Dorret I. Boomsma, Thorkild I. A. Sørensen, Jaakko Kaprio, Karri Silventoinen
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- Twin Research and Human Genetics / Volume 18 / Issue 5 / October 2015
- Published online by Cambridge University Press:
- 04 September 2015, pp. 557-570
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A trend toward greater body size in dizygotic (DZ) than in monozygotic (MZ) twins has been suggested by some but not all studies, and this difference may also vary by age. We analyzed zygosity differences in mean values and variances of height and body mass index (BMI) among male and female twins from infancy to old age. Data were derived from an international database of 54 twin cohorts participating in the COllaborative project of Development of Anthropometrical measures in Twins (CODATwins), and included 842,951 height and BMI measurements from twins aged 1 to 102 years. The results showed that DZ twins were consistently taller than MZ twins, with differences of up to 2.0 cm in childhood and adolescence and up to 0.9 cm in adulthood. Similarly, a greater mean BMI of up to 0.3 kg/m2 in childhood and adolescence and up to 0.2 kg/m2 in adulthood was observed in DZ twins, although the pattern was less consistent. DZ twins presented up to 1.7% greater height and 1.9% greater BMI than MZ twins; these percentage differences were largest in middle and late childhood and decreased with age in both sexes. The variance of height was similar in MZ and DZ twins at most ages. In contrast, the variance of BMI was significantly higher in DZ than in MZ twins, particularly in childhood. In conclusion, DZ twins were generally taller and had greater BMI than MZ twins, but the differences decreased with age in both sexes.
The CODATwins Project: The Cohort Description of Collaborative Project of Development of Anthropometrical Measures in Twins to Study Macro-Environmental Variation in Genetic and Environmental Effects on Anthropometric Traits
- Karri Silventoinen, Aline Jelenkovic, Reijo Sund, Chika Honda, Sari Aaltonen, Yoshie Yokoyama, Adam D. Tarnoki, David L. Tarnoki, Feng Ning, Fuling Ji, Zengchang Pang, Juan R. Ordoñana, Juan F. Sánchez-Romera, Lucia Colodro-Conde, S. Alexandra Burt, Kelly L. Klump, Sarah E. Medland, Grant W. Montgomery, Christian Kandler, Tom A. McAdams, Thalia C. Eley, Alice M. Gregory, Kimberly J. Saudino, Lise Dubois, Michel Boivin, Claire M. A. Haworth, Robert Plomin, Sevgi Y. Öncel, Fazil Aliev, Maria A. Stazi, Corrado Fagnani, Cristina D’Ippolito, Jeffrey M. Craig, Richard Saffery, Sisira H. Siribaddana, Matthew Hotopf, Athula Sumathipala, Timothy Spector, Massimo Mangino, Genevieve Lachance, Margaret Gatz, David A. Butler, Gombojav Bayasgalan, Danshiitsoodol Narandalai, Duarte L. Freitas, José Antonio Maia, K. Paige Harden, Elliot M. Tucker-Drob, Kaare Christensen, Axel Skytthe, Kirsten O. Kyvik, Changhee Hong, Youngsook Chong, Catherine A. Derom, Robert F. Vlietinck, Ruth J. F. Loos, Wendy Cozen, Amie E. Hwang, Thomas M. Mack, Mingguang He, Xiaohu Ding, Billy Chang, Judy L. Silberg, Lindon J. Eaves, Hermine H. Maes, Tessa L. Cutler, John L. Hopper, Kelly Aujard, Patrik K. E. Magnusson, Nancy L. Pedersen, Anna K. Dahl Aslan, Yun-Mi Song, Sarah Yang, Kayoung Lee, Laura A. Baker, Catherine Tuvblad, Morten Bjerregaard-Andersen, Henning Beck-Nielsen, Morten Sodemann, Kauko Heikkilä, Qihua Tan, Dongfeng Zhang, Gary E. Swan, Ruth Krasnow, Kerry L. Jang, Ariel Knafo-Noam, David Mankuta, Lior Abramson, Paul Lichtenstein, Robert F. Krueger, Matt McGue, Shandell Pahlen, Per Tynelius, Glen E. Duncan, Dedra Buchwald, Robin P. Corley, Brooke M. Huibregtse, Tracy L. Nelson, Keith E. Whitfield, Carol E. Franz, William S. Kremen, Michael J. Lyons, Syuichi Ooki, Ingunn Brandt, Thomas Sevenius Nilsen, Fujio Inui, Mikio Watanabe, Meike Bartels, Toos C. E. M. van Beijsterveldt, Jane Wardle, Clare H. Llewellyn, Abigail Fisher, Esther Rebato, Nicholas G. Martin, Yoshinori Iwatani, Kazuo Hayakawa, Finn Rasmussen, Joohon Sung, Jennifer R. Harris, Gonneke Willemsen, Andreas Busjahn, Jack H. Goldberg, Dorret I. Boomsma, Yoon-Mi Hur, Thorkild I. A. Sørensen, Jaakko Kaprio
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- Twin Research and Human Genetics / Volume 18 / Issue 4 / August 2015
- Published online by Cambridge University Press:
- 27 May 2015, pp. 348-360
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For over 100 years, the genetics of human anthropometric traits has attracted scientific interest. In particular, height and body mass index (BMI, calculated as kg/m2) have been under intensive genetic research. However, it is still largely unknown whether and how heritability estimates vary between human populations. Opportunities to address this question have increased recently because of the establishment of many new twin cohorts and the increasing accumulation of data in established twin cohorts. We started a new research project to analyze systematically (1) the variation of heritability estimates of height, BMI and their trajectories over the life course between birth cohorts, ethnicities and countries, and (2) to study the effects of birth-related factors, education and smoking on these anthropometric traits and whether these effects vary between twin cohorts. We identified 67 twin projects, including both monozygotic (MZ) and dizygotic (DZ) twins, using various sources. We asked for individual level data on height and weight including repeated measurements, birth related traits, background variables, education and smoking. By the end of 2014, 48 projects participated. Together, we have 893,458 height and weight measures (52% females) from 434,723 twin individuals, including 201,192 complete twin pairs (40% monozygotic, 40% same-sex dizygotic and 20% opposite-sex dizygotic) representing 22 countries. This project demonstrates that large-scale international twin studies are feasible and can promote the use of existing data for novel research purposes.
Contributors
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- By Mitchell Aboulafia, Frederick Adams, Marilyn McCord Adams, Robert M. Adams, Laird Addis, James W. Allard, David Allison, William P. Alston, Karl Ameriks, C. Anthony Anderson, David Leech Anderson, Lanier Anderson, Roger Ariew, David Armstrong, Denis G. Arnold, E. J. Ashworth, Margaret Atherton, Robin Attfield, Bruce Aune, Edward Wilson Averill, Jody Azzouni, Kent Bach, Andrew Bailey, Lynne Rudder Baker, Thomas R. Baldwin, Jon Barwise, George Bealer, William Bechtel, Lawrence C. Becker, Mark A. Bedau, Ernst Behler, José A. Benardete, Ermanno Bencivenga, Jan Berg, Michael Bergmann, Robert L. Bernasconi, Sven Bernecker, Bernard Berofsky, Rod Bertolet, Charles J. Beyer, Christian Beyer, Joseph Bien, Joseph Bien, Peg Birmingham, Ivan Boh, James Bohman, Daniel Bonevac, Laurence BonJour, William J. Bouwsma, Raymond D. Bradley, Myles Brand, Richard B. Brandt, Michael E. Bratman, Stephen E. Braude, Daniel Breazeale, Angela Breitenbach, Jason Bridges, David O. Brink, Gordon G. Brittan, Justin Broackes, Dan W. Brock, Aaron Bronfman, Jeffrey E. Brower, Bartosz Brozek, Anthony Brueckner, Jeffrey Bub, Lara Buchak, Otavio Bueno, Ann E. Bumpus, Robert W. Burch, John Burgess, Arthur W. Burks, Panayot Butchvarov, Robert E. Butts, Marina Bykova, Patrick Byrne, David Carr, Noël Carroll, Edward S. Casey, Victor Caston, Victor Caston, Albert Casullo, Robert L. Causey, Alan K. L. Chan, Ruth Chang, Deen K. Chatterjee, Andrew Chignell, Roderick M. Chisholm, Kelly J. Clark, E. J. Coffman, Robin Collins, Brian P. Copenhaver, John Corcoran, John Cottingham, Roger Crisp, Frederick J. Crosson, Antonio S. Cua, Phillip D. Cummins, Martin Curd, Adam Cureton, Andrew Cutrofello, Stephen Darwall, Paul Sheldon Davies, Wayne A. Davis, Timothy Joseph Day, Claudio de Almeida, Mario De Caro, Mario De Caro, John Deigh, C. F. Delaney, Daniel C. Dennett, Michael R. DePaul, Michael Detlefsen, Daniel Trent Devereux, Philip E. Devine, John M. Dillon, Martin C. 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One and Two Dimensional Arrays of Membrane Proteins Stabilized by Amphipol
- Wanatchaporn Arunmanee, J. Robin Harris, Jeremy H Lakey
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- By Rose Teteki Abbey, K. C. Abraham, David Tuesday Adamo, LeRoy H. Aden, Efrain Agosto, Victor Aguilan, Gillian T. W. Ahlgren, Charanjit Kaur AjitSingh, Dorothy B E A Akoto, Giuseppe Alberigo, Daniel E. Albrecht, Ruth Albrecht, Daniel O. Aleshire, Urs Altermatt, Anand Amaladass, Michael Amaladoss, James N. Amanze, Lesley G. Anderson, Thomas C. Anderson, Victor Anderson, Hope S. Antone, María Pilar Aquino, Paula Arai, Victorio Araya Guillén, S. Wesley Ariarajah, Ellen T. Armour, Brett Gregory Armstrong, Atsuhiro Asano, Naim Stifan Ateek, Mahmoud Ayoub, John Alembillah Azumah, Mercedes L. García Bachmann, Irena Backus, J. Wayne Baker, Mieke Bal, Lewis V. Baldwin, William Barbieri, António Barbosa da Silva, David Basinger, Bolaji Olukemi Bateye, Oswald Bayer, Daniel H. Bays, Rosalie Beck, Nancy Elizabeth Bedford, Guy-Thomas Bedouelle, Chorbishop Seely Beggiani, Wolfgang Behringer, Christopher M. Bellitto, Byard Bennett, Harold V. Bennett, Teresa Berger, Miguel A. 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Van Bavel, Steven Vanderputten, Peter Van der Veer, Huub Van de Sandt, Louis Van Tongeren, Luke A. Veronis, Noel Villalba, Ramón Vinke, Tim Vivian, David Voas, Elena Volkova, Katharina von Kellenbach, Elina Vuola, Timothy Wadkins, Elaine M. Wainwright, Randi Jones Walker, Dewey D. Wallace, Jerry Walls, Michael J. Walsh, Philip Walters, Janet Walton, Jonathan L. Walton, Wang Xiaochao, Patricia A. Ward, David Harrington Watt, Herold D. Weiss, Laurence L. Welborn, Sharon D. Welch, Timothy Wengert, Traci C. West, Merold Westphal, David Wetherell, Barbara Wheeler, Carolinne White, Jean-Paul Wiest, Frans Wijsen, Terry L. Wilder, Felix Wilfred, Rebecca Wilkin, Daniel H. Williams, D. Newell Williams, Michael A. Williams, Vincent L. Wimbush, Gabriele Winkler, Anders Winroth, Lauri Emílio Wirth, James A. Wiseman, Ebba Witt-Brattström, Teofil Wojciechowski, John Wolffe, Kenman L. Wong, Wong Wai Ching, Linda Woodhead, Wendy M. Wright, Rose Wu, Keith E. Yandell, Gale A. Yee, Viktor Yelensky, Yeo Khiok-Khng, Gustav K. K. Yeung, Angela Yiu, Amos Yong, Yong Ting Jin, You Bin, Youhanna Nessim Youssef, Eliana Yunes, Robert Michael Zaller, Valarie H. Ziegler, Barbara Brown Zikmund, Joyce Ann Zimmerman, Aurora Zlotnik, Zhuo Xinping
- Edited by Daniel Patte, Vanderbilt University, Tennessee
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- The Cambridge Dictionary of Christianity
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- 05 August 2012
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- 20 September 2010, pp xi-xliv
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Contributors
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- By Phillip L. Ackerman, Neil Anderson, Jens B. Asendorpf, R. Michael Bagby, Michael Harris Bond, Gregory J. Boyle, Andrea L. Briggs, Giles St J. Burch, Turhan Canli, David Canter, Gianvittorio Caprara, Charles S. Carver, Douglas F. Cellar, Gordon Claridge, Susan Cloninger, Elisabeth D. Conradt, Philip J. Corr, Sharon Dawe, Ian J. Deary, Boele De Raad, Edward L. Deci, Colin G. DeYoung, M. Brent Donnellan, Juris G. Draguns, Marko Elovainio, Aurelio José Figueredo, David C. Funder, Paul Gladden, Rapson Gomez, Samuel D. Gosling, Jeremy R. Gray, Robert D. Hare, B. Austin Harley, Edward Helmes, Robert Hogan, Lauri A. Jensen-Campbell, Daniel Nelson Jones, Mika Kivimäki, Jennifer M. Knack, James T. Lamiell, Natalie J. Loxton, Geoff MacDonald, Gerald Matthews, Robert R. McCrae, Mario Mikulincer, Stephanie N. Mullins-Sweatt, Marcus R. Munafò, Vickie Nam, Craig S. Newmann, Rainer Reisenzein, Madeline Rex-Lear, Richard W. Robins, Michael D. Robinson, Mary K. Rothbart, Richard M. Ryan, Gerard Saucier, Michael F. Scheier, Constantine Sedikides, Phillip R. Shaver, Brad E. Sheese, Yuichi Shoda, Ronald E. Smith, Alice F. Stuhlmacher, Rhonda Swickert, Avril Thorne, David D. Vachon, Geneva Vásquez, Michele Vecchione, Seth A. Wagerman, Fiona Warren, Hannelore Weber, Thomas A. Widiger, Pedro Sofio Abril Wolf, Donna Youngs, Moshe Zeidner
- Edited by Philip J. Corr, University of East Anglia, Gerald Matthews, University of Cincinnati
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- The Cambridge Handbook of Personality Psychology
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- 05 June 2012
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- 16 July 2009, pp xv-xvii
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- By Graham Allan, Donna M. Allen, Irwin Altman, Arthur Aron, Donald H. Baucom, Steven R. H. Beach, Ellen Berscheid, Rosemary Blieszner, Jeffrey Boase, Tyfany M. J. Boettcher, Barbara B. Brown, Abraham P. Buunk, Lorne Campbell, Daniel J. Canary, Rodney Cate, John P. Caughlin, Mahnaz Charania, Jennie Y. Chen, F. Scott Christopher, Jennifer A. Clarke, Marilyn Coleman, W. Andrew Collins, Michael K. Coolsen, Nathan R. Cottle, Carolyn E. Cutrona, Marianne Dainton, Valerian J. Derlega, Lisa M. Diamond, Pieternel Dijkstra, Steve Duck, Pearl A. Dykstra, Norman B. Epstein, Beverley Fehr, Frank D. Fincham, Helen E. Fisher, Julie Fitness, Garth J. O. Fletcher, Myron D. Friesen, Lawrence Ganong, Kelli A. Gardner, Jenny de Jong Gierveld, Robin Goodwin, Christine R. Gray, Kathryn Greene, David W. Harris, Willard W. Hartup, John H. Harvey, Kathi L. Heffner, Ted L. Huston, William J. Ickes, Emily A. Impett, Michael P. Johnson, Deborah J. Jones, Deborah A. Kashy, Janice K. Kiecolt‐Glaser, Jeffrey L. Kirchner, Brighid M. Kleinman, Galena H. Kline, Mark L. Knapp, Ascan Koerner, Jean‐Philippe Laurenceau, Kim Leon, Timothy J. Loving, Stephanie D. Madsen, Howard J. Markman, Alicia Mathews, Mario Mikulincer, Patricia Noller, Nickola C. Overall, Letitia Anne Peplau, Daniel Perlman, Sally Planalp, Urmila Pillay, Nicole D. Pleasant, Caryl E. Rusbult, Barbara R. Sarason, Irwin G. Sarason, Phillip R. Shaver, Alan L. Sillars, Jeffry A. Simpson, Susan Sprecher, Susan Stanton, Greg Strong, Catherine A. Surra, Anita L. Vangelisti, C. Arthur VanLear, Theo van Tilburg, Barry Wellman, Amy Wenzel, Carol M. Werner, Adam R. West, Sarah W. Whitton, Heike A. Winterheld
- Edited by Anita L. Vangelisti, University of Texas, Austin, Daniel Perlman, University of British Columbia, Vancouver
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- The Cambridge Handbook of Personal Relationships
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- 05 June 2012
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- 05 June 2006, pp xvii-xxii
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Looking Backward, Looking Forward: MLA Members Speak
- April Alliston, Elizabeth Ammons, Jean Arnold, Nina Baym, Sandra L. Beckett, Peter G. Beidler, Roger A. Berger, Sandra Bermann, J.J. Wilson, Troy Boone, Alison Booth, Wayne C. Booth, James Phelan, Marie Borroff, Ihab Hassan, Ulrich Weisstein, Zack Bowen, Jill Campbell, Dan Campion, Jay Caplan, Maurice Charney, Beverly Lyon Clark, Robert A. Colby, Thomas C. Coleman III, Nicole Cooley, Richard Dellamora, Morris Dickstein, Terrell Dixon, Emory Elliott, Caryl Emerson, Ann W. Engar, Lars Engle, Kai Hammermeister, N. N. Feltes, Mary Anne Ferguson, Annie Finch, Shelley Fisher Fishkin, Jerry Aline Flieger, Norman Friedman, Rosemarie Garland-Thomson, Sandra M. Gilbert, Laurie Grobman, George Guida, Liselotte Gumpel, R. K. Gupta, Florence Howe, Cathy L. Jrade, Richard A. Kaye, Calhoun Winton, Murray Krieger, Robert Langbaum, Richard A. Lanham, Marilee Lindemann, Paul Michael Lützeler, Thomas J. Lynn, Juliet Flower MacCannell, Michelle A. Massé, Irving Massey, Georges May, Christian W. Hallstein, Gita May, Lucy McDiarmid, Ellen Messer-Davidow, Koritha Mitchell, Robin Smiles, Kenyatta Albeny, George Monteiro, Joel Myerson, Alan Nadel, Ashton Nichols, Jeffrey Nishimura, Neal Oxenhandler, David Palumbo-Liu, Vincent P. Pecora, David Porter, Nancy Potter, Ronald C. Rosbottom, Elias L. Rivers, Gerhard F. Strasser, J. L. Styan, Marianna De Marco Torgovnick, Gary Totten, David van Leer, Asha Varadharajan, Orrin N. C. Wang, Sharon Willis, Louise E. Wright, Donald A. Yates, Takayuki Yokota-Murakami, Richard E. Zeikowitz, Angelika Bammer, Dale Bauer, Karl Beckson, Betsy A. Bowen, Stacey Donohue, Sheila Emerson, Gwendolyn Audrey Foster, Jay L. Halio, Karl Kroeber, Terence Hawkes, William B. Hunter, Mary Jambus, Willard F. King, Nancy K. Miller, Jody Norton, Ann Pellegrini, S. P. Rosenbaum, Lorie Roth, Robert Scholes, Joanne Shattock, Rosemary T. VanArsdel, Alfred Bendixen, Alarma Kathleen Brown, Michael J. Kiskis, Debra A. Castillo, Rey Chow, John F. Crossen, Robert F. Fleissner, Regenia Gagnier, Nicholas Howe, M. Thomas Inge, Frank Mehring, Hyungji Park, Jahan Ramazani, Kenneth M. Roemer, Deborah D. Rogers, A. LaVonne Brown Ruoff, Regina M. Schwartz, John T. Shawcross, Brenda R. Silver, Andrew von Hendy, Virginia Wright Wexman, Britta Zangen, A. Owen Aldridge, Paula R. Backscheider, Roland Bartel, E. M. Forster, Milton Birnbaum, Jonathan Bishop, Crystal Downing, Frank H. Ellis, Roberto Forns-Broggi, James R. Giles, Mary E. Giles, Susan Blair Green, Madelyn Gutwirth, Constance B. Hieatt, Titi Adepitan, Edgar C. Knowlton, Jr., Emanuel Mussman, Sally Todd Nelson, Robert O. Preyer, David Diego Rodriguez, Guy Stern, James Thorpe, Robert J. Wilson, Rebecca S. Beal, Joyce Simutis, Betsy Bowden, Sara Cooper, Wheeler Winston Dixon, Tarek el Ariss, Richard Jewell, John W. Kronik, Wendy Martin, Stuart Y. McDougal, Hugo Méndez-Ramírez, Ivy Schweitzer, Armand E. Singer, G. Thomas Tanselle, Tom Bishop, Mary Ann Caws, Marcel Gutwirth, Christophe Ippolito, Lawrence D. Kritzman, James Longenbach, Tim McCracken, Wolfe S. Molitor, Diane Quantic, Gregory Rabassa, Ellen M. Tsagaris, Anthony C. Yu, Betty Jean Craige, Wendell V. Harris, J. Hillis Miller, Jesse G. Swan, Helene Zimmer-Loew, Peter Berek, James Chandler, Hanna K. Charney, Philip Cohen, Judith Fetterley, Herbert Lindenberger, Julia Reinhard Lupton, Maximillian E. Novak, Richard Ohmann, Marjorie Perloff, Mark Reynolds, James Sledd, Harriet Turner, Marie Umeh, Flavia Aloya, Regina Barreca, Konrad Bieber, Ellis Hanson, William J. Hyde, Holly A. Laird, David Leverenz, Allen Michie, J. Wesley Miller, Marvin Rosenberg, Daniel R. Schwarz, Elizabeth Welt Trahan, Jean Fagan Yellin
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- PMLA / Publications of the Modern Language Association of America / Volume 115 / Issue 7 / December 2000
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- 23 October 2020, pp. 1986-2078
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- December 2000
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Negative Staining: Historical Background and Technical Development
- J. Robin Harris
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- Microscopy Today / Volume 5 / Issue 2 / March 1997
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- 14 March 2018, pp. 10-13
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- March 1997
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There is a considerable body of information of a technical and review nature on negative staining elsewhere in the literature (Bremner et al., 1992; Harris and Home, 1991, 1994; Hayatand Miller, 1990; Holzenburg, 1988; Home, 1991; Nermut, 1991; Spiess et al., 1987; Valentine and Home, 1962); therefore, I shall attempt to avoid undue repetition and present the current laboratory approaches with which I am personally familiar and have achieved some technical success. After considering the range of procedures necessary for the production of carbon and carbon-plastic support films (sometimes termed substrates) emphasis will be placed upon the droplet negative staining technique (Harris and Agutter, 1970; Harris and Horne, 1991). I was introduced to this approach by Ennio Lucio Benedetti in his laboratory, at the start of my doctoral studies in 1966 (Anderson, 1966; Benedetti and Emmelot, 1965,1968) and with minor variations it is still useful for many biological applications.
Negative Staining and Cryoelectron Microscopy
- J. Robin Harris
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- Journal:
- Microscopy Today / Volume 5 / Issue 1 / January 1997
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- 14 March 2018, p. 18
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- January 1997
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Negative Stains Containing Trehalose: Application to Tubular and Filamentous Structures
- J. Robin Harris, Max Gerber, Wolfgang Gebauer, Wolfgang Wernicke, Jürgen Markl
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- Microscopy and Microanalysis / Volume 2 / Issue 1 / February 1996
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- 30 July 2003, pp. 43-52
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- February 1996
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Several examples are presented that show the successful application of uranyl acetate and ammonium molybdate negative staining in the presence of trehalose for TEM studies of filamentous and tubular structures. The principal benefit to be gained from the inclusion of trehalose stems from the considerably reduced flattening of the large tubular structures and the greater orientational freedom of single molecules due to an increased depth of the negative stain in the presence of trehalose. Trehalose is likely to provide considerable protection to protein molecules and their assemblies during the drying of negatively stained specimens. Some reduction in the excessive density imparted by uranyl acetate around large assemblies is also achieved. Nevertheless, in the presence of 1% (w/v) trehalose, it is desirable to increase the concentration of negative stain to 5% (w/v) for ammonium molybdate and to 4% for uranyl acetate to produce satisfactory image contrast. In general, the ammonium molybdate-trehalose negative stain is more satisfactory than the uranyl acetate-trehalose combination, because of the greater electron beam sensitivity of the uranyl negative stain. Reassembled taxol-stabilized pig brain microtubules, together with collagen fibrils, sperm tails, helical filaments, and reassociated hemocyanin (KLH2), all from the giant keyhole limpet Megathura crenulata, have been studied by negative staining in the presence of trehalose. In all cases satisfactory TEM imaging conditions were readily obtained on the specimens, as long as regions of excessively deep stain were avoided.