Mapping transcriptomic vector fields of single cells.

Single-cell (sc)RNA-seq, together with RNA velocity and metabolic labeling, reveals cellular states and transitions at unprecedented resolution. Fully exploiting these data, however, requires kinetic models capable of unveiling governing regulatory functions. Here, we introduce an analytical framework dynamo (https://github.com/aristoteleo/dynamo-release), which infers absolute RNA velocity, reconstructs continuous vector fields that predict cell fates, employs differential geometry to extract underlying regulations, and ultimately predicts optimal reprogramming paths and perturbation outcomes. We highlight dynamo's power to overcome fundamental limitations of conventional splicing-based RNA velocity analyses to enable accurate velocity estimations on a metabolically labeled human hematopoiesis scRNA-seq dataset. Furthermore, differential geometry analyses reveal mechanisms driving early megakaryocyte appearance and elucidate asymmetrical regulation within the PU.1-GATA1 circuit. Leveraging the least-action-path method, dynamo accurately predicts drivers of numerous hematopoietic transitions. Finally, in silico perturbations predict cell-fate diversions induced by gene perturbations. Dynamo, thus, represents an important step in advancing quantitative and predictive theories of cell-state transitions.

A theoretical perspective on Waddington's genetic assimilation experiments.

Genetic assimilation is the process by which a phenotype that is initially induced by an environmental stimulus becomes stably inherited in the absence of the stimulus after a few generations of selection. While the concept has attracted much debate after being introduced by C. H. Waddington 70 y ago, there have been few experiments to quantitatively characterize the phenomenon. Here, we revisit and organize the results of Waddington's original experiments and follow-up studies that attempted to replicate his results. We then present a theoretical model to illustrate the process of genetic assimilation and highlight several aspects that we think require further quantitative studies, including the gradual increase of penetrance, the statistics of delay in assimilation, and the frequency of unviability during selection. Our model captures Waddington's picture of developmental paths in a canalized landscape using a stochastic dynamical system with alternative trajectories that can be controlled by either external signals or internal variables. It also reconciles two descriptions of the phenomenon-Waddington's, expressed in terms of an individual organism's developmental paths, and that of Bateman in terms of the population distribution crossing a hypothetical threshold. Our results provide theoretical insight into the concepts of canalization, phenotypic plasticity, and genetic assimilation.

Precision of tissue patterning is controlled by dynamical properties of gene regulatory networks.

During development, gene regulatory networks allocate cell fates by partitioning tissues into spatially organised domains of gene expression. How the sharp boundaries that delineate these gene expression patterns arise, despite the stochasticity associated with gene regulation, is poorly understood. We show, in the vertebrate neural tube, using perturbations of coding and regulatory regions, that the structure of the regulatory network contributes to boundary precision. This is achieved, not by reducing noise in individual genes, but by the configuration of the network modulating the ability of stochastic fluctuations to initiate gene expression changes. We use a computational screen to identify network properties that influence boundary precision, revealing two dynamical mechanisms by which small gene circuits attenuate the effect of noise in order to increase patterning precision. These results highlight design principles of gene regulatory networks that produce precise patterns of gene expression.

Pillars of theoretical biology: "Biochemical systems analysis, I, II and III".

Michael Savageau's Biochemical Systems Analysis I, II, IIIpapers, published in volumes 25 and 26 of the journal,kickstarted a research programme that originated many of the core concepts and tools of Systems Biology. This article briefly summarizes these papers anddiscusses the most relevant developments in Biochemical Systems Theory since their publication.

Quality of life and its influencing factors on children with asthma in China: a comparative study before and during the COVID-19 pandemic.

OBJECTIVE: This study compares the level of quality of life (QoL) and its influencing factors on children with asthma before and during the COVID-19 pandemic. METHODS: The study carried out cross-sectional surveys on children with asthma and their parents in China before and during the epidemic. Data were collected using a demographic questionnaire, the Family Management Scale for Children with Asthma (FMSCA), and the Pediatric Asthma Quality of Life Questionnaire (PAQLQ). Participants from before the epidemic were matched by their propensity score in a 1:1 ratio with individuals from during the epidemic. The level of QoL of children with asthma was subsequently analyzed. Both univariate analysis and multiple linear regression were employed to identify the influencing factors. RESULTS: Compared to their level before the epidemic, the total score of PAQLQ and its three dimensions decreased during the epidemic. Regression analysis revealed that before the epidemic, the total score of PAQLQ was significantly associated with follow-up visits, attendance of asthma lectures, and the total score of FMSCA (p < 0.05). During the epidemic, the total score of the PAQLQ was significantly associated with three dimensions of the FMSCA (future expectation, children identity, and views of condition), and two classifications of the family management styles (FMS) (enduring and accommodating) (p < 0.05). CONCLUSION: The QoL of children with asthma deteriorated during the epidemic. Influencing factors changed during the epidemic, with more emphasis on the family environment. Future intervention strategies need to take into account the development of interactions between children and environmental forces.

Exploring the world of food with families: perspectives of low-income families on factors influencing their food choices.

OBJECTIVE: The aim of this study was to investigate the social and environmental factors involved in the food decision-making processes of families living on lower incomes on the Island of Ireland. DESIGN: A qualitative design was employed for this study, using photovoice and creative mapping methods. Parents were requested to take photos and draw maps of their food environments. Interviews were then conducted with parents, using the materials produced by parents as a cue to discuss their food environments, influences and decision-making processes around food choices. SETTING: The participants were interviewed online via Microsoft Teams. PARTICIPANTS: The participants were parents or guardians of children between the ages of 2 and 18 who self-defined as 'living on a tight budget'. RESULTS: Twenty-eight participants were recruited and interviewed for this study, including twelve parents in Northern Ireland and sixteen in the Republic of Ireland. The findings were mapped on to Bronfenbrenner's Ecological Systems Theory and showed that multiple, overlapping and intersecting factors at the individual, micro-, meso-, exo-, macro- and chrono-system were implicated in family food choices. Upstream factors in particular, including structural, policy and commercial determinants, appear to be significant drivers of behaviour. CONCLUSIONS: While the findings suggest that a complex range of factors are involved in family food choices, it is clear that policy measures and regulations are needed to stave off the impacts of rising social inequality and food poverty. Health promoters should strive to find non-stigmatising interventions to bridge the nutritional divide experienced by lower-income families.

An ecosystemic perspective of the factors affecting the learning experiences of learners with dyslexia in mainstream schools in England.

A systematic literature review (SLR) of seven papers written between 2015 and 2021 explored the educational experiences of learners with dyslexia in mainstream schools in England from an ecosystemic perspective and how to improve the situation. The analysis employed keywords for database searches and followed the PRISMA flow protocol. It synthesised evidence using thematic analysis and identified seven themes: dyslexia challenges; differential treatment; negative stereotypes; early intervention; teachers' training; power dynamics; and collaboration. The results suggest that several factors can influence the learning experiences of learners with dyslexia in English mainstream schools. Similarly, such factors can, in turn, be dependent on education policies. On that premise, this systematic literature review recommends that to promote positive learning experiences for learners with dyslexia, classroom strategies targeting interventions should be supported with broader environmental strategies shaping individuals' learning experience and offer support from different perspectives. A whole-school approach to providing intervention, teachers' training, parents and school partnerships, and professional collaboration can improve learners' educational experiences. A further recommendation is for learning interventions to target all learners, to prevent differential treatment of learners with dyslexia and to avoid them standing out from their peers and creating a negative experience.

Age-related differences in the interplay of fluency and complexity in Chinese-speaking seniors' oral narratives.

BACKGROUND: Previous studies on language production in normal ageing have primarily focused on distinct dimensions of older adults' spoken language performance, such as fluency and complexity. However, little attention has been paid to the complex, interconnected relations between these dimensions. Additionally, older adults have been treated as a homogeneous group, with little consideration for the differential characteristics of language performance across different stages of ageing. AIMS: This study aims to investigate how increasing age impacts Chinese seniors' oral language performance, focusing on fluency (articulation rate and dysfluency rate), complexity (lexical and syntactic) and the potential interactions between these dimensions. METHODS & PROCEDURES: Spontaneous oral narratives were collected from 60 normally ageing individuals, who were categorised into three groups: young-old (60-69 years old), middle-old (70-79 years old) and old-old (≥80 years old). Four measures for assessing language performance, namely, articulation rate, dysfluency rate, lexical complexity and syntactic complexity, were derived from the oral narratives. Dynamic systems techniques, including moving correlations, locally estimated scatterplot smoothing and Monte Carlo simulations, were employed for data analysis. OUTCOMES & RESULTS: This study revealed two major findings. First, across different age groups, the seniors' oral narratives significantly differed in the aspect of articulation rate and syntactic complexity. Specifically, both the young-old and the middle-old groups exhibited significantly higher articulation rates than the old-old group; the middle-old group also demonstrated significantly higher syntactic complexity compared to the old-old group. Second, the distinct subsystems (i.e., articulation rate, dysfluency rate, lexical and syntactic complexity) of seniors' oral narratives demonstrated varying interactions across different stages of ageing. While these subsystems tended to coordinate with each other in young-old individuals, they exhibited a greater tendency to compete in middle-old and old-old individuals. CONCLUSIONS & IMPLICATIONS: The findings reveal that subsystems of older adults' oral narratives display varying interactions with the increase of age, indicating that focusing solely on one dimension of language performance may result in inaccurate or misleading conclusions. Therefore, a multi-index comprehensive assessment should be employed for the enhancement of clinical evaluations of language performance in older adults. Additionally, it is vital to consider the interactional patterns (i.e., support or competition) between language subsystems when assessing language performance in normal ageing. WHAT THIS PAPER ADDS: What is already known on the subject Previous research on language production in normal ageing has primarily focused on distinct dimensions of older adults' spoken language performance, such as fluency, vocabulary richness and grammatical complexity, overlooking the intricate interconnections between these dimensions. However, investigating these connections is significant for a thorough and in-depth understanding of language production in late adulthood, which operates as a system comprising interconnected components. Furthermore, existing studies have predominantly treated older adults as a homogeneous group, comparing their language use to that of young people. This approach lacks justification, given the substantial variations in language use among seniors at different stages of ageing. What this paper adds to existing knowledge The present findings illuminate the dynamic nature of language production in normal ageing. Not only do the distinct dimensions or subsystems of older adults' oral narratives (e.g., articulation rate, dysfluency rate, syntactic complexity) change with age, but more important, the ways in which these subsystems interact with each other also evolve with age, resulting in changing states of spoken language production in the ageing process. More specifically, our study provides evidence that the interactions among subsystems of older adults' oral narratives predominately transition from supportive relationships in earlier stages to competitive ones at later stages of ageing. What are the potential or actual clinical implications of this work? The present study suggests the use of multiple linguistic indices related to various aspects of language performance to assess the spoken language production of older adults. This is highlighted by the observation that various dimensions of older adults' oral narratives continuously interact with one another across different stages of ageing, and hence focusing solely on one dimension of language performance tends to lead to inaccurate or misleading results. Additionally, the patterns of interaction (i.e., support or competition) between different dimensions of language performance may reflect older adults' capacity to coordinate and control attentional resources and therefore should be taken into consideration in clinical evaluations of language performance in older adults.

Medical student experiences of equality, diversity, and inclusion: content analysis of student feedback using Bronfenbrenner's ecological systems theory.

BACKGROUND: Issues relating to equality, diversity, and inclusion (EDI) significantly impact on medical student achievement and wellbeing. Interventions have been introduced at curricular and organisational levels, yet progress in addressing these issues remains limited. Timely evaluation is needed to assess effectiveness of interventions, and to explore issues and interactions in learning environments impacting on student experience. We introduced an anonymous question concerning students' experiences of EDI into routine online student feedback questionnaires, to scope the nature of ongoing issues and develop greater understanding of students' experiences in our programme environment. Ecological systems theory, which conceptualizes learning as a function of complex social interactions, determined by characteristics of individual learners and their environment, provides a framework for understanding. METHODS: Free-text responses regarding experiences of EDI gathered over 20 months from all programme years (n = 760) were pooled for analysis, providing a holistic overview of experiences in the learning environment. A counting exercise identified broad categories reported by students. Content analysis of the qualitative dataset was undertaken. Bronfenbrenner's ecological systems theory was applied as a framework to demonstrate interdependencies between respondents' experiences and environments, and associated impacts. RESULTS: Three hundred and seventy-six responses were received relating to wide-ranging EDI issues, most frequently gender or ethnicity. Responses mapped onto all areas of the ecological systems model, with frequent links between subsystems, indicating considerable complexity and interdependencies. Interpersonal interactions and associated impacts like exclusion were frequently discussed. Differential experiences of EDI-related issues in medical school compared to clinical settings were reported. Impacts of institutional leadership and wider societal norms were considered by respondents. Respondents discussed their need for awareness of EDI with reference to future professional practice. CONCLUSIONS: Implementation of a regular free-text evaluation question allowed data-gathering across cohorts and throughout several stages of the curriculum, illuminating student experience. Connections established demonstrated intersectionality, and how environment and other factors interact, impacting on student experiences. Students experience EDI-related issues on multiple levels within the educational environment, with consequent impacts on learning. Any successful approach towards tackling issues and promoting equity of opportunity for all requires multi-level actions and widespread culture change. Students can offer fresh and distinct perspectives regarding change needed, to complement and diversify perspectives provided by staff and organisational leadership. Student voice should be enabled to shape change.

"100 Things I Wish Someone Would Have Told Me": Everyday Challenges Parents Face While Caring for Their Children With a Tracheostomy.

Equitable access to appropriate care, emergency department services, and in-home support aids are needed to minimize the occurrences of adverse events that have a significant impact on families. However, many families of children with medical complexity (CMC) lack consistent care due to issues of health inequity. We conducted 11 qualitative interviews with primary caregivers who were asked about their experiences of providing care to children who have a tracheostomy and are supported by multiple life-saving machines at home. Guided by ecological systems theory, we identified three themes that contextualize the lived experiences of the participants who expressed needs that arose from poor interactions within the mesosystem. Findings convey participant frustrations that result from insufficient support, ineffective training, and inadequate healthcare coverage. Although each theme is organized systematically to emphasize specific concerns within the mesosystem, together these themes emphasize the inextricable relationship between daily needs with systemic barriers to care. We provide a discussion of these needs with a broader context that also impacts the perceived quality of care among families managing the needs of their children who are supported by life-saving technology. By addressing existing challenges and identifying opportunities for improvement within the healthcare system, we seek to contribute to the collective effort of advocating for ethical systemic change on behalf of CMC and their families.

Couple differentiation and health-related quality of life.

The purpose of this study was to examine whether couple differentiation influenced mental and physical health-related quality of life in couple members. Data for this study were derived from a larger study at a couple a family therapy clinic. One hundred and thirty-three couples were included in a latent profile analysis, and seventy-two couples were included in analyses of mean differences. The latent profile analysis resulted in three distinct groups by level of couple differentiation: high, moderate, or low in differentiation of self. Analyses of variance indicated evidence that couple differentiation influenced health-related quality-of-life measures. Findings are discussed in the context of Bowen Family Systems Theory and the existing literature.

A special section: Contributions of family science to anti-racism efforts.

Concomitant with a growing recognition of demographic shifts toward greater racial/ethnic diversity in the United States and widespread depictions of racial injustice, desires for increased racial/ethnic tolerance and inclusivity have been expressed in various sectors of U.S. society, including education, healthcare, and business. However, the literature on effective strategies and interventions for advancing anti-racism, or efforts to reduce racial/ethnic injustice, is minimal and underdeveloped. The family science field, characterized by rich theories on human systems and interactions, strategies for changing interpersonal dynamics, and the recognition that perceived knowledge is dependent on sociopolitical location, has much to offer the study of strategies to actualize increased racial/ethnic equity. The articles in this special section demonstrate potential contributions family science can make to the endeavor for racial/ethnic equity, through presenting theoretical, empirical, and practice innovations and findings steeped in the family science orientation toward addressing systems, cycles, and change.

The ecological dynamics of trumpet improvisation.

The nature of music improvisation continues to provide an interesting showcase of the multifaceted and skilful ways we engage with and act within our environments. Improvising musicians are somehow able to generate musical material in real time that adaptively navigates musical situations. In this article I explore the broader aspects of improvised activity-such as our bodily interactions with the instrument and environment-as they relate to improvised music-making. I do so by drawing upon principles from the embodied cognitive sciences, namely ecological and dynamical systems approaches. Firstly, I introduce the concept of affordances to illustrate the bidirectional relationship between improvisor and environment. I then take a dynamical view, exploring the ways that a trumpet player coordinates their body with their instrument and engages with trumpet affordances in order to navigate musical situations. I continue this dynamical view, taking the improviser to be an adaptive system whose behaviours are self-organised responses to a set of constraints. To conclude, I situate my research within the wider 4E approach. I advocate that 'E' approaches, which take seriously the role of the body-instrument-environment relationship, provide an insightful perspective on the nature of improvisation.

"You Can Do So Much Better Than What They Expect": An Arts-Based Engagement Ethnography on School Integration With Newcomer Youth.

Newcomer adolescents make up a large minority of Canada's population and their positive integration experiences with education systems across the country are critical for both their development and the country's long-term success. The current study examined newcomer adolescents' (n = 4, between 16 and 18 years old) integration experiences using an arts-based engagement ethnography to understand what influences their positive integration into the school system. Artifacts, interview, and focus group data were analyzed systematically using ethnographic research guidelines. Five structures were identified: (1) barriers to advancement at individual, school, and macro levels, (2) fluctuating relationship with cultural identity, (3) limited trust in systems, (4) resilience through independent learning, and (5) facilitating factors to positive integration experiences at the family and school level. In keeping with a relational developmental systems theory framework, each structure accounts for multiple inter- and intra-individual factors at multiple environmental levels. These findings outline considerations for systemic issues in academic institutions and offer suggestions for how institutions can better support newcomer adolescents.

Farm to Preschool Programs and Its Impact on Children's Dietary Health: Evaluation Through Bronfenbrenner's Socio-Ecological Model.

Children's development is shaped by the world around them. According to Bronfenbrenner's theory, children are influenced by direct interactions and the broader environment, which includes family, community, and society. This concept aligns with initiatives like farm-to-preschool programs. These programs forge connections between communities and local food sources, introducing gardening and nutritional education. This approach aligns seamlessly with Bronfenbrenner's theory, creating a multi-layered learning experience and fostering children's healthier eating habits. This review delves into how farm-to-preschool efforts enhance young children's diets through the ecological model evaluation framework, encompassing health, education, economics, and the environment.

Phenotype Design Space Provides a Mechanistic Framework Relating Molecular Parameters to Phenotype Diversity Available for Selection.

Two long-standing challenges in theoretical population genetics and evolution are predicting the distribution of phenotype diversity generated by mutation and available for selection, and determining the interaction of mutation, selection and drift to characterize evolutionary equilibria and dynamics. More fundamental for enabling such predictions is the current inability to causally link genotype to phenotype. There are three major mechanistic mappings required for such a linking - genetic sequence to kinetic parameters of the molecular processes, kinetic parameters to biochemical system phenotypes, and biochemical phenotypes to organismal phenotypes. This article introduces a theoretical framework, the Phenotype Design Space (PDS) framework, for addressing these challenges by focusing on the mapping of kinetic parameters to biochemical system phenotypes. It provides a quantitative theory whose key features include (1) a mathematically rigorous definition of phenotype based on biochemical kinetics, (2) enumeration of the full phenotypic repertoire, and (3) functional characterization of each phenotype independent of its context-dependent selection or fitness contributions. This framework is built on Design Space methods that relate system phenotypes to genetically determined parameters and environmentally determined variables. It also has the potential to automate prediction of phenotype-specific mutation rate constants and equilibrium distributions of phenotype diversity in microbial populations undergoing steady-state exponential growth, which provides an ideal reference to which more realistic cases can be compared. Although the framework is quite general and flexible, the details will undoubtedly differ for different functions, organisms and contexts. Here a hypothetical case study involving a small molecular system, a primordial circadian clock, is used to introduce this framework and to illustrate its use in a particular case. The framework is built on fundamental biochemical kinetics. Thus, the foundation is based on linear algebra and reasonable physical assumptions, which provide numerous opportunities for experimental testing and further elaboration to deal with complex multicellular organisms that are currently beyond its scope. The discussion provides a comparison of results from the PDS framework with those from other approaches in theoretical population genetics.

Spiraling Risk: Visualizing the multilevel factors that socially pattern HIV risk among gay, bisexual & other men who have sex with men using Complex Systems Theory.

PURPOSE OF REVIEW: Global disparities in HIV infection, particularly among gay, bisexual, and other men who have sex with men (GBMSM), indicate the importance of exploring the multi-level processes that shape HIV's spread. We used Complex Systems Theory and the PRISMA guidelines to conduct a systematic review of 63 global reviews to understand how HIV is socially patterned among GBMSM. The purpose was to conduct a thematic analysis of the reviews to (1) synthesize the multi-level risk factors of HIV risk, (2) categorize risk across the socioecological model, and (3) develop a conceptual model that visualizes the interrelated factors that shape GBMSMS's HIV "risk." RECENT FINDINGS: We included 49 studies of high and moderate quality studies. Results indicated that GBMSM's HIV risk stems from the individual, interpersonal, and structural levels of the socioecological model. We identified a few themes that shape GBMSM's risk of HIV infection related to biomedical prevention methods; sexual and sex-seeking behaviors; behavioral prevention methods; individual-level characteristics and syndemic infections; lived experiences and interpersonal relationships; country-level income; country-level HIV prevalence; and structural stigma. The multi-level factors, in tandem, serve to perpetuate GBMSM's risk of HIV infection globally. The amalgamation of our thematic analyses from our systematic reviews of reviews suggests that the risk of HIV infection operates in an emergent, dynamic, and complex nature across multiple levels of the socioecological model. Applying complex systems theory indicates how multilevel factors create a dynamic and reinforcing system of HIV risk among GBMSM.

The Dynamics of Pasture-Herbivores-Carnivores with Sigmoidal Density Dependent Harvesting.

We investigate biomass-herbivore-carnivore (top predator) interactions in terms of a tritrophic dynamical systems model. The harvesting rates of the herbivores and the top predators are described by means of a sigmoidal function of the herbivores density and the top predator density, respectively. The main focus in this study is on the dynamics as a function of the natural mortality and the maximal harvesting rate of the top predators. We identify parameter regimes for which we have non-existence of equilibrium points as well as necessary conditions for the existence of such states of the modelling framework. The system does not possess any finite equilibrium states in the regime of high herbivore mortality. In the regime of a high consumption rate of the herbivores and low mortality rates of the top predator, an asymptotically stable finite equilibrium state exists. For this positive equilibrium to exist the mortality of the top predator should not exceed a certain threshold level. We also detect regimes producing coexistence of equilibrium states and their respective stability properties. In the regime of negligible harvesting of the top predator level, we observe a finite window of the natural top predator mortality rates for which oscillations in the top predator-, the herbivore- and the biomass level take place. The lower and upper bound of this window correspond to two Hopf bifurcation points. We also identify a bifurcation diagram using the top predator harvesting rate as a control variable. Using this diagram we detect several saddle node- and Hopf bifurcation points as well as regimes for which we have coexistence of interior equilibrium states, bistability and relaxation type of oscillations.

Toddlers' expressions indicate that they track agent-object interactions but do not detect false object representations.

In the theory of mind debate, a middle position between nativism and conceptual change theory has gained traction. This position states that children younger than 4 years track agent-object relations (by building "records" of others' experiences) without cognizing how agents represent-or misrepresent-the objects they encounter. We tested these claims with 3.5-year-olds using puppet shows geared to evoke suspenseful expressions. In two experiments (N = 90), children watched an agent approach an object that looked like her favorite food but was inedible. In Experiment 1, children showed tense expressions when an agent's real food item was, unbeknownst to her, replaced with a fake food item. Children, however, showed no signs of understanding that the agent would mistake the deceptive object for food. Consistent with this, children's expressions in Experiment 2 did not differ when the agent approached a deceptive object compared with when she approached a non-deceptive object. The experiments support the middle position's view that toddlers track agent-object interactions but fail to recognize when agents misrepresent objects.

The structural and social determinants of Alzheimer's disease related dementias.

INTRODUCTION: The projected growth of Alzheimer's disease (AD) and AD-related dementia (ADRD) cases by midcentury has expanded the research field and impelled new lines of inquiry into structural and social determinants of health (S/SDOH) as fundamental drivers of disparities in AD/ADRD. METHODS: In this review, we employ Bronfenbrenner's ecological systems theory as a framework to posit how S/SDOH impact AD/ADRD risk and outcomes. RESULTS: Bronfenbrenner defined the "macrosystem" as the realm of power (structural) systems that drive S/SDOH and that are the root cause of health disparities. These root causes have been discussed little to date in relation to AD/ADRD, and thus, macrosystem influences, such as racism, classism, sexism, and homophobia, are the emphasis in this paper. DISCUSSION: Under Bronfenbrenner's macrosystem framework, we highlight key quantitative and qualitative studies linking S/SDOH with AD/ADRD, identify scientific gaps in the literature, and propose guidance for future research. HIGHLIGHTS: Ecological systems theory links structural/social determinants to AD/ADRD. Structural/social determinants accrue and interact over the life course to impact AD/ADRD. Macrosystem is made up of societal norms, beliefs, values, and practices (e.g., laws). Most macro-level determinants have been understudied in the AD/ADRD literature.