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1. Impact of age-related changes in buccal epithelial cells on pediatric epigenetic biomarker research.

Author

Merrill, Sarah, Konwar, Chaini, Fatima, Fizza, Dever, Kristy, MacIsaac, Julia, Letourneau, Nicole, Giesbrecht, Gerald, Dewey, Deborah, England-Mason, Gillian, Lewis, Candace, Wang, Dennis, Teh, Ai, Meaney, Michael, Gonzalez, Andrea, Noll, Jennie, De Weerth, Carolina, Bush, Nicole, ODonnell, Kieran, Stewart, S, and Kobor, Michael

Subjects
Humans, Child, Adolescent, Mouth Mucosa, Child, Preschool, Female, Male, Epigenesis, Genetic, Young Adult, Epithelial Cells, DNA Methylation, Infant, Biomarkers, Cheek, Age Factors, Adult, Hydrocortisone
Abstract

Cheek swabs, heterogeneous samples consisting primarily of buccal epithelial cells, are widely used in pediatric DNA methylation studies and biomarker creation. However, the decrease in buccal proportion with age in adults remains unexamined in childhood. We analyzed cheek swabs from 4626 typically developing children 2-months to 20-years-old. Estimated buccal proportion declined throughout childhood with both increasing chronological and predicted epigenetic age. However, buccal proportion did not associate with age throughout adolescence. Variability in buccal proportion increased with age through the entire developmental range. These trends held inversely true for neutrophil proportions. Correcting for buccal proportion attenuated the weak association with PedBE age acceleration to non-significance during initial estimation. Notably, correcting for buccal proportion attenuated the association of PedBE age acceleration with obsessive-compulsive disorder and strengthened the association with diurnal cortisol slope. Thus, the age-related change in childrens oral cells is a crucial consideration for cell type-sensitive research.

Published
2025

3. Shared and unique transcriptomic signatures of antidepressant and probiotics action in the mammalian brain

Author

Rayan, Nirmala Arul, Aow, Jonathan, Lim, Michelle Gek Liang, Arcego, Danusa Mar, Ryan, Richard, Nourbakhsh, Nooshin, de Lima, Randriely Merscher Sobreira, Craig, Kelly, Zhang, Tie Yuan, Goh, Yeek Teck, Sun, Alfred Xuyang, Tompkins, Thomas, Bronner, Stéphane, Binda, Sylvie, Diorio, Josie, Parent, Carine, Meaney, Michael J., and Prabhakar, Shyam

Published
2024
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4. The Promise of MOOCs Revisited? Demographics of Learners Preparing for University

Author

Meaney, Michael J. and Fikes, Tom

Abstract

This paper leverages cluster analysis to provide insight into how traditionally underrepresented learners engage with entry-level massive open online courses (MOOCs) intended to lower the barrier to university enrolment, produced by a major research university in the United States. From an initial sample of 260,239 learners, we cluster analyze a subset of data from 29,083 participants who submitted an assignment in one of nine entry-level MOOC courses. Manhattan distance and Gower distance measures are computed based on engagement, achievement, and demographic data. To our knowledge, this marks one of the first such uses of Gower distance to cluster mixed variable data to explore fairness and equity in the MOOC literature. The clusters are derived from CLARA and PAM algorithms, enriched by demographic data, with a particular focus on education level, as well as approximated socioeconomic status (SES) for a smaller subset of learners. Results indicate that learners without a college degree are more likely to be high-performing compared to college-educated learners. Learners from lower SES backgrounds are just as likely to be successful as learners from middle and higher SES backgrounds. While MOOCs have struggled to improve access to learning, more fair and equitable outcomes for traditionally underrepresented learners are possible.

Published
2023

5. Associations between Social Adversity and Biomarkers of Inflammation, Stress, and Aging in Children

Author

Pantell, Matthew S, Silveira, Patricia P, de Mendonça Filho, Euclides José, Wing, Holly, Brown, Erika M, Keeton, Victoria F, Pokhvisneva, Irina, O’Donnell, Kieran J, Neuhaus, John, Hessler, Danielle, Meaney, Michael J, Adler, Nancy E, and Gottlieb, Laura M

Subjects
Paediatrics, Biomedical and Clinical Sciences, Pediatric Research Initiative, Prevention, Behavioral and Social Science, Brain Disorders, Pediatric, Aetiology, 2.3 Psychological, social and economic factors, Inflammatory and immune system, Paediatrics and Reproductive Medicine, Public Health and Health Services, Pediatrics
Abstract

BackgroundPrior work has found relationships between childhood social adversity and biomarkers of stress, but knowledge gaps remain. To help address these gaps, we explored associations between social adversity and biomarkers of inflammation (interleukin-1β [IL-1β], IL-6, IL-8, tumor necrosis factor-alpha [TNF-α], and salivary cytokine hierarchical "clusters" based on the three interleukins), neuroendocrine function (cortisol, cortisone, dehydroepiandrosterone, testosterone, and progesterone), neuromodulation (N-arachidonoylethanolamine, stearoylethanolamine, oleoylethanolamide, and palmitoylethanolamide), and epigenetic aging (Pediatric-Buccal-Epigenetic clock).MethodsWe collected biomarker samples of children ages 0-17 recruited from an acute care pediatrics clinic and examined their associations with caregiver-endorsed education, income, social risk factors, and cumulative adversity. We calculated regression-adjusted means for each biomarker and compared associations with social factors using Wald tests. We used logistic regression to predict being in the highest cytokine cluster based on social predictors.ResultsOur final sample included 537 children but varied based on each biomarker. Cumulative social adversity was significantly associated with having higher levels of all inflammatory markers and with cortisol, displaying a U-shaped distribution. There were no significant relationships between cumulative social adversity and cortisone, neuromodulation biomarkers or epigenetic aging.ConclusionOur findings support prior work suggesting that social stress exposures contribute to increased inflammation in children.ImpactOur study is one of the largest studies examining associations between childhood social adversity and biomarkers of inflammation, neuroendocrine function, neuromodulation, and epigenetic aging. It is one of the largest studies to link childhood social adversity to biomarkers of inflammation, and the first of which we are aware to link cumulative social adversity to cytokine clusters. It is also one of the largest studies to examine associations between steroids and epigenetic aging among children, and one of the only studies of which we are aware to examine associations between social adversity and endocannabinoids among children.Clinical trial registrationNCT02746393.

Published
2024

6. A global multicohort study to map subcortical brain development and cognition in infancy and early childhood.

Author

Alex, Ann, Aguate, Fernando, Botteron, Kelly, Buss, Claudia, Chong, Yap-Seng, Dager, Stephen, Donald, Kirsten, Entringer, Sonja, Fair, Damien, Fortier, Marielle, Gaab, Nadine, Gilmore, John, Girault, Jessica, Graham, Alice, Groenewold, Nynke, Hazlett, Heather, Lin, Weili, Meaney, Michael, Piven, Joseph, Qiu, Anqi, Rasmussen, Jerod, Roos, Annerine, Schultz, Robert, Skeide, Michael, Stein, Dan, Styner, Martin, Thompson, Paul, Turesky, Ted, Wadhwa, Pathik, Zar, Heather, Zöllei, Lilla, de Los Campos, Gustavo, and Knickmeyer, Rebecca

Subjects
Male, Female, Humans, Infant, Newborn, Child, Preschool, Child, Premature Birth, Cognition, Brain, Neuroimaging, Magnetic Resonance Imaging
Abstract

The human brain grows quickly during infancy and early childhood, but factors influencing brain maturation in this period remain poorly understood. To address this gap, we harmonized data from eight diverse cohorts, creating one of the largest pediatric neuroimaging datasets to date focused on birth to 6 years of age. We mapped the developmental trajectory of intracranial and subcortical volumes in ∼2,000 children and studied how sociodemographic factors and adverse birth outcomes influence brain structure and cognition. The amygdala was the first subcortical volume to mature, whereas the thalamus exhibited protracted development. Males had larger brain volumes than females, and children born preterm or with low birthweight showed catch-up growth with age. Socioeconomic factors exerted region- and time-specific effects. Regarding cognition, males scored lower than females; preterm birth affected all developmental areas tested, and socioeconomic factors affected visual reception and receptive language. Brain-cognition correlations revealed region-specific associations.

Published
2024

7. Exploring multi-omics and clinical characteristics linked to accelerated biological aging in Asian women of reproductive age: insights from the S-PRESTO study

Author

Chen, Li, Tan, Karen Mei-Ling, Xu, Jia, Mishra, Priti, Mir, Sartaj Ahmad, Gong, Min, Narasimhan, Kothandaraman, Ng, Bryan, Lai, Jun Shi, Tint, Mya Thway, Cai, Shirong, Sadananthan, Suresh Anand, Michael, Navin, Yaligar, Jadegoud, Velan, Sambasivam Sendhil, Leow, Melvin Khee Shing, Tan, Kok Hian, Chan, Jerry, Meaney, Michael J., Chan, Shiao-Yng, Chong, Yap Seng, and Eriksson, Johan G.

Published
2024
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10. Linking specific biological signatures to different childhood adversities: findings from the HERO project.

Author

de Mendonça Filho, Euclides, Pokhvisneva, Irina, Maalouf, Christina, Parent, Carine, Mliner, Shanna, Slopen, Natalie, Williams, David, Boyce, William, Levitt, Pat, Nelson, Charles, Gunnar, Megan, Meaney, Michael, Shonkoff, Jack, Silveira, Patricia, and Bush, Nicole

Subjects
Humans, Child, Hydrocortisone, Cortisone, Tumor Necrosis Factor-alpha, Stress, Psychological, Saliva, Hypothalamo-Hypophyseal System, Pituitary-Adrenal System, Dehydroepiandrosterone
Abstract

BACKGROUND: Although investigations have begun to differentiate biological and neurobiological responses to a variety of adversities, studies considering both endocrine and immune function in the same datasets are limited. METHODS: Associations between proximal (family functioning, caregiver depression, and anxiety) and distal (SES-D; socioeconomic disadvantage) early-life adversities with salivary inflammatory biomarkers (IL-1β, IL-6, IL-8, and TNF-α) and hair HPA markers (cortisol, cortisone, and dehydroepiandrosterone) were examined in two samples of young U.S. children (N = 142; N = 145). RESULTS: Children exposed to higher SES-D had higher levels of TNF-α (B = 0.13, p = 0.011), IL-1β (B = 0.10, p = 0.033), and DHEA (B = 0.16, p = 0.011). Higher family dysfunction was associated with higher cortisol (B = 0.08, p = 0.033) and cortisone (B = 0.05, p = 0.003). An interaction between SES-D and family dysfunction was observed for cortisol levels (p = 0.020) whereby children exposed to lower/average levels of SES-D exhibited a positive association between family dysfunction and cortisol levels, whereas children exposed to high levels of SES-D did not. These findings were partially replicated in the second sample. CONCLUSIONS: Our results indicate that these biological response systems may react differently to different forms of early-life adversity. IMPACT: Different forms of early-life adversity have varied stress signatures, and investigations of early-life adversities with inflammation and HPA markers are lacking. Children with higher socioeconomic disadvantage had higher TNF-α, IL-1β, and DHEA. Higher family dysfunction was associated with higher hair cortisol and cortisone levels, and the association between family dysfunction and cortisol was moderated by socioeconomic disadvantage. Biological response systems (immune and endocrine) were differentially associated with distinct forms of early-life adversities.

Published
2023

13. Neurobiology of Anxiety Disorders

Author

Meaney, Michael J., Liebowitz, Michael R., David Leonardo, E., Schulze, Thomas G., Section editor, Laje, Gonzalo, Section editor, Tasman, Allan, editor, Riba, Michelle B., editor, Alarcón, Renato D., editor, Alfonso, César A., editor, Kanba, Shigenobu, editor, Lecic-Tosevski, Dusica, editor, Ndetei, David M., editor, Ng, Chee H., editor, and Schulze, Thomas G., editor

Published
2024
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14. Household Social Needs, Emotional Functioning, and Stress in Low-Income Latinx Children and their Mothers.

Author

Keeton, Victoria F, Bell, Janice F, Drake, Christiana, Fernandez Y Garcia, Erik O, Pantell, Matthew, Hessler, Danielle, Wing, Holly, Silveira, Patricia P, O'Donnell, Kieran J, de Mendonça Filho, Euclides José, Meaney, Michael J, and Gottlieb, Laura M

Subjects
Child emotional health, Latinx, hair cortisol, maternal stress, social needs, Clinical Research, Prevention, Mental Health, Pediatric, Mind and Body, Behavioral and Social Science, Rare Diseases, Basic Behavioral and Social Science, Reproductive health and childbirth, Good Health and Well Being, Maternal stress, Social needs, Hair cortisol, Public Health and Health Services, Psychology, Linguistics, Family Studies
Abstract

Latinx families may be particularly vulnerable to emotional dysfunction, due to higher rates of economic hardship and complex social influences in this population. Little is known about the impact of environmental stressors such as unmet social needs and maternal stress on the emotional health of Latinx children from low-income families. We conducted secondary analyses using survey and biomarker data from 432 Latinx children and mothers collected in a separate study. We used binomial and multinomial logistic regression to test if household social needs, or maternal perceived stress or hair cortisol concentration (HCC), predicted child measures of emotional functioning or child HCC, independent of relevant sociodemographic factors. Approximately 40% of children in the sample had symptoms consistent with emotional dysfunction, and over 37% of households reported five or more social needs. High perceived maternal stress predicted higher odds of child emotional dysfunction (OR = 2.15; 95% CI [1.14, 4.04]; p = 0.01), and high maternal HCC was positively associated with high child HCC (OR = 10.60; 95% CI [4.20, 26.74]; p < 0.01). Most individual household social needs, as well as the level of household social need, were not independently associated with child emotional dysfunction or child HCC. Our findings begin to define a framework for understanding emotional health, stress, and resilience when caring for Latinx children and mothers living with high levels of social need, and the need for integrated mental health and social needs screening and interventions in settings that serve this population.

Published
2023

20. Atypical Brain Aging and Its Association With Working Memory Performance in Major Depressive Disorder

Author

Adamson, Chris, Adler, Sophie, Alexander-Bloch, Aaron F., Anagnostou, Evdokia, Anderson, Kevin M., Areces-Gonzalez, Ariosky, Astle, Duncan E., Auyeung, Bonnie, Ayub, Muhammad, Bae, Jong Bin, Ball, Gareth, Baron-Cohen, Simon, Beare, Richard, Bedford, Saashi A., Benegal, Vivek, Bethlehem, Richard A.I., Beyer, Frauke, Blangero, John, Cábez, Manuel Blesa, Boardman, James P., Borzage, Matthew, Bosch-Bayard, Jorge F., Bourke, Niall, Bullmore, Edward T., Calhoun, Vince D., Chakravarty, Mallar M., Chen, Christina, Chertavian, Casey, Chetelat, Gaël, Chong, Yap S., Corvin, Aiden, Costantino, Manuela, Courchesne, Eric, Crivello, Fabrice, Cropley, Vanessa L., Crosbie, Jennifer, Crossley, Nicolas, Delarue, Marion, Delorme, Richard, Desrivieres, Sylvane, Devenyi, Gabriel, Di Biase, Maria A., Dolan, Ray, Donald, Kirsten A., Donohoe, Gary, Dorfschmidt, Lena, Dunlop, Katharine, Edwards, Anthony D., Elison, Jed T., Ellis, Cameron T., Elman, Jeremy A., Eyler, Lisa, Fair, Damien A., Fletcher, Paul C., Fonagy, Peter, Franz, Carol E., Galan-Garcia, Lidice, Gholipour, Ali, Giedd, Jay, Gilmore, John H., Glahn, David C., Goodyer, Ian M., Grant, P.E., Groenewold, Nynke A., Gudapati, Shreya, Gunning, Faith M., Gur, Raquel E., Gur, Ruben C., Hammill, Christopher F., Hansson, Oskar, Hedden, Trey, Heinz, Andreas, Henson, Richard N., Heuer, Katja, Hoare, Jacqueline, Holla, Bharath, Holmes, Avram J., Huang, Hao, Ipser, Jonathan, Jack, Clifford R., Jr., Jackowski, Andrea P., Jia, Tianye, Jones, David T., Jones, Peter B., Kahn, Rene S., Karlsson, Hasse, Karlsson, Linnea, Kawashima, Ryuta, Kelley, Elizabeth A., Kern, Silke, Kim, Ki-Woong, Kitzbichler, Manfred G., Kremen, William S., Lalonde, François, Landeau, Brigitte, Lerch, Jason, Lewis, John D., Li, Jiao, Liao, Wei, Liston, Conor, Lombardo, Michael V., Lv, Jinglei, Mallard, Travis T., Marcelis, Machteld, Mathias, Samuel R., Mazoyer, Bernard, McGuire, Philip, Meaney, Michael J., Mechelli, Andrea, Misic, Bratislav, Morgan, Sarah E., Mothersill, David, Ortinau, Cynthia, Ossenkoppele, Rik, Ouyang, Minhui, Palaniyappan, Lena, Paly, Leo, Pan, Pedro M., Pantelis, Christos, Park, Min Tae M., Paus, Tomas, Pausova, Zdenka, Paz-Linares, Deirel, Binette, Alexa Pichet, Pierce, Karen, Qian, Xing, Qiu, Anqi, Raznahan, Armin, Rittman, Timothy, Rodrigue, Amanda, Rollins, Caitlin K., Romero-Garcia, Rafael, Ronan, Lisa, Rosenberg, Monica D., Rowitch, David H., Salum, Giovanni A., Satterthwaite, Theodore D., Schaare, H. Lina, Schabdach, Jenna, Schachar, Russell J., Schöll, Michael, Schultz, Aaron P., Seidlitz, Jakob, Sharp, David, Shinohara, Russell T., Skoog, Ingmar, Smyser, Christopher D., Sperling, Reisa A., Stein, Dan J., Stolicyn, Aleks, Suckling, John, Sullivan, Gemma, Thyreau, Benjamin, Toro, Roberto, Traut, Nicolas, Tsvetanov, Kamen A., Turk-Browne, Nicholas B., Tuulari, Jetro J., Tzourio, Christophe, Vachon-Presseau, Étienne, Valdes-Sosa, Mitchell J., Valdes-Sosa, Pedro A., Valk, Sofie L., van Amelsvoort, Therese, Vandekar, Simon N., Vasung, Lana, Vértes, Petra E., Victoria, Lindsay W., Villeneuve, Sylvia, Villringer, Arno, Vogel, Jacob W., Wagstyl, Konrad, Wang, Yin-Shan S., Warfield, Simon K., Warrier, Varun, Westman, Eric, Westwater, Margaret L., Whalley, Heather C., White, Simon R., Witte, A. Veronica, Yang, Ning, Yeo, B.T. Thomas, Yun, Hyuk Jin, Zalesky, Andrew, Zar, Heather J., Zettergren, Anna, Zhou, Juan H., Ziauddeen, Hisham, Zimmerman, Dabriel, Zugman, Andre, Zuo, Xi-Nian N., Ho, Natalie C.W., Nogovitsyn, Nikita, Metzak, Paul, Ballester, Pedro L., Hassel, Stefanie, Rotzinger, Susan, Poppenk, Jordan, Lam, Raymond W., Taylor, Valerie H., Milev, Roumen, Frey, Benicio N., Harkness, Kate L., Addington, Jean, and Kennedy, Sidney H.

Published
2024
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23. Seemingly Unrelated Multi-State processes: a Bayesian semiparametric approach

Author

Cremaschi, Andrea, Argiento, Raffele, De Iorio, Maria, Shirong, Cai, Chong, Yap Seng, Meaney, Michael J., and Kee, Michelle Z. L.

Subjects
Statistics - Methodology
Abstract

Many applications in medical statistics as well as in other fields can be described by transitions between multiple states (e.g. from health to disease) experienced by individuals over time. In this context, multi-state models are a popular statistical technique, in particular when the exact transition times are not observed. The key quantities of interest are the transition rates, capturing the instantaneous risk of moving from one state to another. The main contribution of this work is to propose a joint semiparametric model for several possibly related multi-state processes (Seemingly Unrelated Multi-State, SUMS, processes), assuming a Markov structure for the transitions over time. The dependence between different processes is captured by specifying a joint random effect distribution on the transition rates of each process. We assume a flexible random effect distribution, which allows for clustering of the individuals, overdispersion and outliers. Moreover, we employ a graph structure to describe the dependence among processes, exploiting tools from the Gaussian Graphical model literature. It is also possible to include covariate effects. We use our approach to model disease progression in mental health. Posterior inference is performed through a specially devised MCMC algorithm.

Published
2021

24. Realism about Reskilling: Upgrading the Career Prospects of America's Low-Wage Workers. Workforce of the Future Initiative

Author

Brookings Institution, Center for Universal Education, Brookings Institution, Global Economy and Development, Escobari, Marcela, Seyal, Ian, and Meaney, Michael

Abstract

Every person deserves the opportunity for dignified employment that provides living wages and potential for advancement. However, for many in America today, this is far from reality, as they are caught in a cycle of low-wage work, earning poverty wages, and unable to move up in the economy. Local leaders, firms, and workers need to adapt quickly to keep pace with rapid technological innovation and its transformative impact on the U.S. economy. Using reskilling as a focal point, this report aims to provide policymakers with tools to do so by answering the following questions: (1) Who are the nation's low-wage workers, and what are their prospects?; (2) Where are the local opportunities for mobility, and how can policymakers expand them and help low-wage workers transition?; and (3) How can the reskilling infrastructure adapt to the future, foster inclusion, and address the needs of any worker seeking upward mobility? Combined with the previous report, "Growing Cities that Work for All," this report illustrates the trends affecting low-wage work and the implications for leaders aiming to improve worker mobility. [For "Growing Cities that Work for All," see ED602975. Support from Google.org and MasterCard Center for Inclusive Growth.]

Published
2019

28. Understanding Factors that Influence Upskilling

Author

Laguna-Muggenburg, Eduardo, Bhole, Monica, and Meaney, Michael

Subjects
Economics - General Economics
Abstract

We investigate the motivation and means through which individuals expand their skill-set by analyzing a survey of applicants from the Facebook Jobs product. Individuals who report being influenced by their networks or local economy are over 29% more likely to have a postsecondary degree, but peer effects still exist among those who do not acknowledge such influences. Users with postsecondary degrees are more likely to upskill in general, by continuing coursework or applying to higher-skill jobs, though the latter is more common among users across all education backgrounds. These findings indicate that policies aimed at connecting individuals with different educational backgrounds can encourage upskilling. Policies that encourage users to enroll in coursework may not be as effective among individuals with a high school degree or less. Instead, connecting such individuals to opportunities that value skills acquired outside of a formal education, and allow for on-the-job training, may be more effective., Comment: 11 pages, 4 tables, 3 figures

Published
2021

30. Change of pace: How developmental tempo varies to accommodate failed provision of early needs

Author

Roubinov, Danielle, Meaney, Michael J, and Boyce, W Thomas

Subjects
Biomedical and Clinical Sciences, Health Sciences, Pediatric Research Initiative, Pediatric, Generic health relevance, Developmental acceleration and deceleration, HPA axis, Adversity, Gene x environment, Medical and Health Sciences, Psychology and Cognitive Sciences, Behavioral Science & Comparative Psychology, Biomedical and clinical sciences, Health sciences
Abstract

The interplay of genes and environments (GxE) is a fundamental source of variation in behavioral and developmental outcomes. Although the role of developmental time (T) in the unfolding of such interactions has yet to be fully considered, GxE operates within a temporal frame of reference across multiple timescales and degrees of biological complexity. Here, we consider GxExT interactions to understand adversity-induced developmental acceleration or deceleration whereby environmental conditions hasten or hinder children's development. To date, developmental pace changes have been largely explained through a focus on the individual: for example, how adversity "wears down" aging biological systems or how adversity accelerates or decelerates maturation to optimize reproductive fitness. We broaden such theories by positing shifts in developmental pace in response to the parent-child dyad's capacity or incapacity for meeting children's early, physiological and safety needs. We describe empirical evidence and potential neurobiological mechanisms supporting this new conceptualization of developmental acceleration and deceleration. We conclude with suggestions for future research on the developmental consequences of early adverse exposures.

Published
2021

34. A Glucocorticoid-Sensitive Hippocampal Gene Network Moderates the Impact of Early-Life Adversity on Mental Health Outcomes

Author

Arcego, Danusa Mar, Buschdorf, Jan-Paul, O’Toole, Nicholas, Wang, Zihan, Barth, Barbara, Pokhvisneva, Irina, Rayan, Nirmala Arul, Patel, Sachin, de Mendonça Filho, Euclides José, Lee, Patrick, Tan, Jennifer, Koh, Ming Xuan, Sim, Chu Ming, Parent, Carine, de Lima, Randriely Merscher Sobreira, Clappison, Andrew, O’Donnell, Kieran J., Dalmaz, Carla, Arloth, Janine, Provençal, Nadine, Binder, Elisabeth B., Diorio, Josie, Silveira, Patrícia Pelufo, and Meaney, Michael J.

Published
2024
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35. Essays on the design of inclusive learning in Massive Open Online Courses, and implications for educational futures

Author

Meaney, Michael and Sabates, Ricardo

Subjects
Distance Education, Massive Open Online Courses, Educational Technology, Inclusive Learning, Education Policy
Abstract

This thesis examines the tensions and contradictions of Massive Open Online Courses (MOOCs) as a force for more inclusive tertiary education, particularly for adults without a college degree in the United States. Through a multimethodological research approach yielding three discrete papers, presented as chapters, this work seeks to augment and clarify the existing MOOCs literature across conceptual, quantitative, and qualitative domains. The first paper develops a conceptual framework, 'hegemonic design bias,' that describes the socio-technical development ecosystem in which MOOCs are embedded. This framework helps account for why MOOCs have yet to serve as a democratising force in education by highlighting the processes and constraints that bias MOOC production toward the already well-educated. The potential economic implications of these developments are also considered. The second paper provides insight into how underrepresented learners are engaging with entry-level MOOCs. The exploration of learning analytic data from an initial sample of more than 260,000 enrolees through cluster analysis and multinomial logistic regression indicates that students without a college degree are more likely to be high-performing learners compared to college-educated students in these courses. Additionally, students from approximated lower socioeconomic backgrounds are no less likely to be successful than students from approximated middle and higher socioeconomic backgrounds in these courses. The third paper provides insight into the opportunities and challenges producers face in building inclusive MOOCs through a qualitative analysis of six semi-structured interviews. The interviews unearthed diverse conceptions of inclusion among producers that reflect a sincere normative commitment to make inclusive MOOCs, though the conceptions were quite distinct and fragmented. Producers were intentional about utilising best-practice pedagogy, as well as innovative program design, to include diverse learners. Innovative technology partners helped create interactive, unique experiences, but this also led to challenges in harmonising the design process and required the considerable influence of intermediary actors. To conclude, I briefly consider the implications of these findings for research, practice, and policy, with particular attention to how the public and social sectors can incentivise improved design of MOOCs with the specific intent of helping adults without college degrees develop human capital in order to remain economically resilient amidst the disruptions of skills-biased technological change.

Published
2021
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38. DCC gene network in the prefrontal cortex is associated with total brain volume in childhood

Author

Morgunova, Alice, Pokhvisneva, Irina, Nolvi, Saara, Entringer, Sonja, Wadhwa, Pathik, Gilmore, John, Styner, Martin, Buss, Claudia, Sassi, Roberto Britto, Hall, Geoffrey BC, O'Donnell, Kieran J, Meaney, Michael J, Silveira, Patricia P, and Flores, Cecilia A

Subjects
Pediatric, Brain Disorders, Genetics, Basic Behavioral and Social Science, Clinical Research, Neurosciences, Behavioral and Social Science, Aetiology, 2.1 Biological and endogenous factors, Neurological, Good Health and Well Being, Adult, Brain, Child, Child, Preschool, Cohort Studies, DCC Receptor, Female, Gene Regulatory Networks, Genome-Wide Association Study, Humans, Infant, Infant, Newborn, Male, Multifactorial Inheritance, Polymorphism, Single Nucleotide, Prefrontal Cortex, Clinical Sciences, Cognitive Sciences, Psychiatry
Abstract

BackgroundGenetic variation in the guidance cue DCC gene is linked to psychopathologies involving dysfunction in the prefrontal cortex. We created an expression-based polygenic risk score (ePRS) based on the DCC coexpression gene network in the prefrontal cortex, hypothesizing that it would be associated with individual differences in total brain volume.MethodsWe filtered single nucleotide polymorphisms (SNPs) from genes coexpressed with DCC in the prefrontal cortex obtained from an adult postmortem donors database (BrainEAC) for genes enriched in children 1.5 to 11 years old (BrainSpan). The SNPs were weighted by their effect size in predicting gene expression in the prefrontal cortex, multiplied by their allele number based on an individual's genotype data, and then summarized into an ePRS. We evaluated associations between the DCC ePRS and total brain volume in children in 2 community-based cohorts: the Maternal Adversity, Vulnerability and Neurodevelopment (MAVAN) and University of California, Irvine (UCI) projects. For comparison, we calculated a conventional PRS based on a genome-wide association study of total brain volume.ResultsHigher ePRS was associated with higher total brain volume in children 8 to 10 years old (β = 0.212, p = 0.043; n = 88). The conventional PRS at several different thresholds did not predict total brain volume in this cohort. A replication analysis in an independent cohort of newborns from the UCI study showed an association between the ePRS and newborn total brain volume (β = 0.101, p = 0.048; n = 80). The genes included in the ePRS demonstrated high levels of coexpression throughout the lifespan and are primarily involved in regulating cellular function.LimitationsThe relatively small sample size and age differences between the main and replication cohorts were limitations.ConclusionOur findings suggest that the DCC coexpression network in the prefrontal cortex is critically involved in whole brain development during the first decade of life. Genes comprising the ePRS are involved in gene translation control and cell adhesion, and their expression in the prefrontal cortex at different stages of life provides a snapshot of their dynamic recruitment.

Published
2021

41. Plasma lipidomic profiling reveals metabolic adaptations to pregnancy and signatures of cardiometabolic risk: a preconception and longitudinal cohort study

Author

Chen, Li, Mir, Sartaj Ahmad, Bendt, Anne K., Chua, Esther W. L., Narasimhan, Kothandaraman, Tan, Karen Mei-Ling, Loy, See Ling, Tan, Kok Hian, Shek, Lynette P., Chan, Jerry, Yap, Fabian, Meaney, Michael J., Chan, Shiao-Yng, Chong, Yap Seng, Gluckman, Peter D., Eriksson, Johan G., Karnani, Neerja, and Wenk, Markus R.

Published
2023
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42. The PedBE clock accurately estimates DNA methylation age in pediatric buccal cells.

Author

McEwen, Lisa M, O'Donnell, Kieran J, McGill, Megan G, Edgar, Rachel D, Jones, Meaghan J, MacIsaac, Julia L, Lin, David Tse Shen, Ramadori, Katia, Morin, Alexander, Gladish, Nicole, Garg, Elika, Unternaehrer, Eva, Pokhvisneva, Irina, Karnani, Neerja, Kee, Michelle ZL, Klengel, Torsten, Adler, Nancy E, Barr, Ronald G, Letourneau, Nicole, Giesbrecht, Gerald F, Reynolds, James N, Czamara, Darina, Armstrong, Jeffrey M, Essex, Marilyn J, de Weerth, Carolina, Beijers, Roseriet, Tollenaar, Marieke S, Bradley, Bekh, Jovanovic, Tanja, Ressler, Kerry J, Steiner, Meir, Entringer, Sonja, Wadhwa, Pathik D, Buss, Claudia, Bush, Nicole R, Binder, Elisabeth B, Boyce, W Thomas, Meaney, Michael J, Horvath, Steve, and Kobor, Michael S

Subjects
Mouth Mucosa, Epithelial Cells, Humans, Cohort Studies, Longitudinal Studies, Epigenesis, Genetic, CpG Islands, Adolescent, Adult, Child, Child, Preschool, Infant, Female, Male, Young Adult, Epigenomics, DNA methylation, adolescence, age, development, epigenetic clock, Human Genome, Genetics, Pediatric, Underpinning research, 1.1 Normal biological development and functioning, Generic health relevance, Good Health and Well Being
Abstract

The development of biological markers of aging has primarily focused on adult samples. Epigenetic clocks are a promising tool for measuring biological age that show impressive accuracy across most tissues and age ranges. In adults, deviations from the DNA methylation (DNAm) age prediction are correlated with several age-related phenotypes, such as mortality and frailty. In children, however, fewer such associations have been made, possibly because DNAm changes are more dynamic in pediatric populations as compared to adults. To address this gap, we aimed to develop a highly accurate, noninvasive, biological measure of age specific to pediatric samples using buccal epithelial cell DNAm. We gathered 1,721 genome-wide DNAm profiles from 11 different cohorts of typically developing individuals aged 0 to 20 y old. Elastic net penalized regression was used to select 94 CpG sites from a training dataset (n = 1,032), with performance assessed in a separate test dataset (n = 689). DNAm at these 94 CpG sites was highly predictive of age in the test cohort (median absolute error = 0.35 y). The Pediatric-Buccal-Epigenetic (PedBE) clock was characterized in additional cohorts, showcasing the accuracy in longitudinal data, the performance in nonbuccal tissues and adult age ranges, and the association with obstetric outcomes. The PedBE tool for measuring biological age in children might help in understanding the environmental and contextual factors that shape the DNA methylome during child development, and how it, in turn, might relate to child health and disease.

Published
2020

45. Preconception sleep quality moderates the association between preconception hair cortisol levels and mental health in pregnant women

Author

Abdul Jafar, Nur K., Tham, Elaine K.H., Eng, Derric Z.H., Yeo, Sherwynn, Rifkin-Graboi, Anne, Gooley, Joshua J., Loy, See Ling, Eriksson, Johan G., Chong, Yap-Seng, Tan, Kok Hian, Chan, Jerry Kok Yen, Chen, Helen, Shek, Lynette Pei-Chi, Gluckman, Peter D., Yap, Fabian, Meaney, Michael J., Broekman, Birit F.P., Kee, Michelle Z.L., and Cai, Shirong

Published
2023
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47. Genetic predisposition to depression and inflammation impacts symptom burden and survival in patients with head and neck cancer: A longitudinal study

Author

Henry, Melissa, Harvey, Raphaële, Chen, Lawrence M., Meaney, Michael, Nguyen, Thi Thu Thao, Kao, Han-Tin, Rosberger, Zeev, Frenkiel, Saul, Hier, Michael, Zeitouni, Anthony, Kost, Karen, Mlynarek, Alex, Richardson, Keith, Greenwood, Celia M.T., Melnychuk, David, Gold, Phil, Chartier, Gabrielle, Black, Martin, Mascarella, Marco, MacDonald, Christina, Sadeghi, Nader, Sultanem, Khalil, Shenouda, Georges, Cury, Fabio, and O'Donnell, Kieran John

Published
2023
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