Historical Constraints Research Articles

Exposure to the antiretroviral drug dolutegravir impairs structure and neurogenesis in a forebrain organoid model of human embryonic cortical development

IntroductionFor many therapeutic drugs, including antiretroviral drugs used to treat people living with HIV-1 (PLWH), we have little data on the potential effects on the developing human brain due to limited access to tissue and historical constraints on the inclusion of pregnant populations in clinical trials. Human induced pluripotent stem cells (iPSCs) offer a new avenue to gain insight on how drugs may impact human cell types representative of the developing central nervous system. To prevent vertical transmission of HIV and promote the health of pregnant PLWH, antiretroviral therapy must be initiated and/or maintained throughout pregnancy. However, many antiretroviral drugs are approved for widespread use following clinical testing only in non-pregnant populations and there may be limited information on potential teratogenicity until pregnancy outcomes are evaluated. The integrase strand transfer inhibitor dolutegravir (DTG) is a frontline antiretroviral drug that is effective in viral suppression of HIV but was previously reported to be associated with a slight increase in the risk for neural tube defects in one study, although this has not been replicated in other cohorts.MethodsTo directly investigate the potential impact of DTG on human cortical neurogenesis, we measured the effects of daily drug exposure on the early stages of corticogenesis in a human iPSC-based forebrain organoid model. We quantified organoid size and structure and analyzed gene and protein expression to evaluate the impact of several doses of DTG on organoid development.ResultsWe observed deficits in organoid structure and impaired neurogenesis in DTG-treated organoids compared to vehicle-treated control organoids after 20 or 40 days in culture. Our highest dose of DTG (10 μM) resulted in significantly smaller organoids with a reduced density of neural rosette structures compared to vehicle-treated controls. Mechanistically, RNA-sequencing and immunohistological analysis suggests dysregulated amino acid transport and activation of the integrated stress response in the DTG-treated organoids, and functionally, a small molecule integrated stress response inhibitor (ISRIB) could partially rescue increased expression of proteins related to cell cycle regulation.DiscussionTogether, these results illustrate the potential for human iPSC-based strategies to reveal biological processes during neurogenesis that may be affected by therapeutic drugs and provide complementary data in relevant human cell types to augment preclinical investigations of drug safety during pregnancy.

Decentering governance models: education policy and school accountability in Post-Devolution Wales

ABSTRACT This paper investigates education policy reform in post-Devolution Wales with a focus on school accountability. Specifically, it provides a historicist analysis of Wales’ decision to abandon publicly mandated school league tables and subsequent accountability reforms. The paper uses the literature on four governance models to investigate successive accountability regimes in Wales through time. These have changed from a Trust and Altruism model, via a Transparent Public Rankings model, to a new, emerging model that relies on self-assessment and collaborative accountability standards. Notably, the Organization for Economic Cooperation and Development (OECD) has played an increasingly important role in shaping this process. Central to our analysis is Mark Bevir and Roderick Rhodes’ decentered theory. The paper argues that governance models need to be understood with reference to the dynamic interplay of historical constraints, power struggles and new belief systems that respond to policy dilemmas. As Wales has embarked on several substantial education policy reform initiatives, the paper demonstrates the importance of a historically informed approach to policy design and implementation which is responsive to competing traditions and beliefs.

On the edge: Conservation genomics of the critically endangered dwarf mountain pine Pherosphaera fitzgeraldii

Pherosphaera fitzgeraldii, the Dwarf Mountain Pine, is a critically endangered conifer restricted to cliff ledges within waterfall spray zones in the Greater Blue Mountains Area of New South Wales, Australia. This species is under threat from pollution, invasive weeds, and limited recruitment, which are contributing to its declining population. Using a comprehensive conservation genomic approach, we assessed the population health of P. fitzgeraldii and developed strategic recommendations for its management.Genomic analysis of P. fitzgeraldii revealed the presence of two distinct genetic groups despite the limited distribution of the species. This genetic structure aligns with prevailing wind currents, indicating potential restrictions to pollen or seed exchange between subpopulations. Furthermore, limited gene flow was observed even among nearby subpopulations, emphasizing the risk of increased genetic differentiation due to ongoing isolation. Clonality is widespread in some subpopulations, and all subpopulations displayed signs of inbreeding and genetic depletion despite subdioecy, indicative of historical constraints on gene flow and small population sizes.We offer genomic-based recommendations for prioritizing conservation sites, enhancing genetic diversity in ex situ collections, and guiding future management. Further studies to uncover the sex determination mechanism of P. fitzgeraldii could help maintain balanced sex ratios in ex situ collections and support future genetic rescue efforts. This study underscores the value of genomics in informing protection and recovery of unique threatened species.

Sustainability of specialized healthcare in economies like Jamaica: Overcoming historical constraints

Small island economies designated as upper-middle-income economies find themselves in the somewhat awkward position of not being viewed as in desperate need of financial support for their healthcare and thus receive severely limited external aid for healthcare. Consequently, countries like Jamaica have had to be self-reliant in funding their health-care systems. This challenge has prompted an early and sustained focus on primary healthcare, recognizing that prevention is better than cure. However, with the success of this strategy and the change in the disease profile from infectious concerns to chronic non-communicable diseases associated with aging, the cost of healthcare has markedly increased. Rapid technological advances in the diagnosis and treatment of specialized conditions have further escalated health-care costs. Funding these increasing health-care costs sustainably is a significant challenge for Jamaica and similarly developed smaller economies, especially given the numerous other demands for scarce funds. One potential solution to this chronic problem is to develop sustainable funding sources within the country, such as through local entrepreneurs and philanthropy. Partnerships for health can be forged, where philanthropic investments play a critical role. This article is the first in a series of two. It explores a relationship between the historical context and the current status of healthcare in Jamaica, which is evaluated in further detail, identifying the existing deficiencies that stem from chronic underinvestment. The second article will discuss the principles of giving, with a focus on philanthropy. Future endeavors will include a formal qualitative study of Jamaica’s wealthiest entrepreneurs to assess their interest in philanthropy and their potential to invest philanthropically in specialized healthcare in Jamaica.

Influences of sociocultural and historical constraints on athletes’ developmental experiences: a case study of baseball in Japan

Many observers have pointed out how baseball in Japan is narrated, taught, and played differently from its counterpart in North America. Hard-work, selfless behaviors, and defensive and collectivistic strategies are described as the basic tenets of Japanese baseball, often referred to as ‘Samurai Baseball’. This paper aims to investigate sports and non-sporting constraints that define this distinct way of perceiving the game. Ecological psychology, arguing individuals’ actions should be investigated at the level of interactions which happen between them and their environment, provides the epistemological foundation for this study, while the Skilled Intentionality Framework, proposing behaviours occur amid specific sets of promoted values, gives the ontological base for investigating proximal and distal influences on Japanese ballplayers’ development. Using Bronfenbrenner’s bioecological model as a theoretical framework, this paper demonstrates how coaches’ strategies and training proposals, as well as players’ skill-acquisition processes, are constrained by socio-cultural-historical features of the culture of reference.

The empire strikes back: the financialization of rental housing – a new frontier of accumulation and precarity

ABSTRACT The financialization of rental housing, driven by post-GFC financial contexts, sees assets concentrated in the hands of corporate landlords aided by technological innovations and state support. Foreclosures and evictions, especially in GFC-affected areas, enable corporate acquisition of property at bargain rates, followed by eviction strategies to increase turnover and rental prices, bypassing regulations. This upward distribution of value is supported by growing labor precarity, intertwined with rising rental prices globally. Labor market precarity, linked to stagnant wages, exacerbates housing precarity, creating new forms of accumulation by dispossession. The hypothesis suggests a convergence in “regulated deregulation,” blending formality and informality through financial processes, digital mechanisms, and public policies. Renting becomes a bridging mechanism, transforming housing into a service, managing time and income generation, with potential scalability through digital mechanisms. This marks a departure from historical constraints, potentially establishing unprecedented connections between informality and finance.

Ultrastructure and phylogenetic significance of spermatozoa in Nemertea

Sperm ultrastructure is frequently employed as a source for phylogenetic inference due to the ease of accessing spermatozoa. Despite being unicellular, sperm cells exhibit a relatively high number of diverse characters and character states. Spermatozoa are subject to strong sexual selection as they are finely tuned for maximizing male reproductive success. Given this strong functional constraint, one might anticipate the emergence of convergent characters in line with similar modes of reproduction. As a result, it might be expected that sperm cells do not possess substantial phylogenetic signal, with functional constraints overshadowing any evolutionary heritage. To test this assumption, we conducted a study on sperm ultrastructure in 11 nemertean species, representing closely related groups and major nemertean lineages. We analyzed these data for their phylogenetic signal within the context of the most recent nemertean phylogenies. Our findings demonstrate that, at all systematic levels, functional constraints imposed by sexual selection, or the mode of reproduction do not supersede the influence of historical constraints on sperm ultrastructure.

Altitudinal variation in soil nematode communities in an alpine mountain region of the eastern Tibetan plateau

Distribution patterns of species diversity in high mountains have received considerable attention in scientific research and conservation efforts. However, our understanding of the corresponding altitudinal patterns of soil fauna across spatial scales, particularly on high-altitude plateaus, remains limited. To address this gap, we conducted a case study on Balang Mountain, located at the eastern margin of the Tibetan Plateau. Our focus was on soil nematodes within an altitudinal range of approximately 3000 to 4000 m. We collected climate, soil, and vegetation data to test multiple hypotheses, including the effects of energy, water availability, productivity, soil resource availability, and pH constraints on nematode communities. Dominance analysis and commonality analysis were employed to determine the relative support of these hypotheses in explaining nematode abundance, diversity, and composition. Beta-diversity, which links local alpha-diversity and regional gamma-diversity, was decomposed into distinct components to elucidate ecological processes along altitude and across diversity facets. Our findings revealed distinct yet significant altitudinal patterns in nematode abundance (concave-down), richness (monotonous decrease), and evenness (concave-up). Water and soil resource availability emerged as dominant factors influencing nematode abundance, while energy and pH played pivotal roles in determining nematode richness. Additionally, water and productivity were identified as the most significant drivers shaping nematode community composition. Furthermore, a significant influence of pH on gamma- and beta-diversities was observed, surpassing the impact of other predictors at a coarse level. Upon decomposing beta-diversities into different components, we discovered that taxa substitution (turnover) and individual substitution (balance-variation) were the primary contributors to community dissimilarity among altitudes, indicating strong effects of environmental sorting or spatial and historical constraints on soil nematode communities. These findings contribute to our understanding of the distribution patterns and processes of soil nematode communities along altitude in alpine ecosystems. Moreover, they offer valuable insights into soil biodiversity distribution and conservation in high-mountain environments.

Mass individualism: The snowman effect

This study critically evaluates contemporary menswear, with a particular focus on the ‘snowman effect’ and mass individualism, to understand the complex dynamics between performativity, gender and socio-styles. It is inspired by the story of ‘Frosty the Snowman’, which illustrates how garments, initially mass-produced, are given life and identity through personalization. This transformation metaphorically represents the fashion industry’s complex relationship between individual expression and societal norms. The article addresses the issue of overconsumption, arguing that it leads to uniform fashion styles despite an abundance of clothing options, thereby increasing the demand for more authentic and personalized fashion. The core of this research examines ‘mass individualism’ within the global fashion industry, exploring its potential to offer sustainable choices while highlighting the challenges and opportunities it presents to major fashion brands. It argues for a shift away from traditional marketing, emphasizing the need for tailored services that meet consumers’ desires for authenticity and individuality. The article also examines the historical constraints on menswear, the evolution of socio-styles and the impact of ‘fit’ on the appropriateness of clothing. It also examines consumer habits and the growing trend towards customization in men’s fashion, particularly in terms of performative individuality and social norms. Finally, the study emphasizes the importance of recognizing the contemporary consumer’s desire for uniqueness and suggests mass customization as a vital strategy for revitalizing the menswear sector, reflecting the changing relationship between fashion, gender performance and socio-styles in contemporary society.

History constrains the evolution of efficient color naming, enabling historical inference

Color naming in natural languages is not arbitrary: It reflects efficient partitions of perceptual color space [T. Regier, P. Kay, N. Khetarpal, Proc. Natl. Acad. Sci. U.S.A. 104, 1436-1441 (2007)] modulated by the relative needs to communicate about different colors [C. Twomey, G. Roberts, D. Brainard, J. Plotkin, Proc. Natl. Acad. Sci. U.S.A. 118, e2109237118 (2021)]. These psychophysical and communicative constraints help explain why languages around the world have remarkably similar, but not identical, mappings of colors to color terms. Languages converge on a small set of efficient representations.But languages also evolve, and the number of terms in a color vocabulary may change over time. Here we show that history, i.e. the existence of an antecedent color vocabulary, acts as a nonadaptive constraint that biases the choice of efficient solution as a language transitions from a vocabulary of size [Formula: see text] to [Formula: see text] terms. Moreover, as efficient vocabularies evolve to include more terms they explore a smaller fraction of all possible efficient vocabularies compared to equally sized vocabularies constructed de novo. This path dependence of the cultural evolution of color naming presents an opportunity. Historical constraints can be used to reconstruct ancestral color vocabularies, allowing us to answer long-standing questions about the evolutionary sequences of color words, and enabling us to draw inferences from phylogenetic patterns of language change.

A history of progressive Doxa: an exploration of Bengali women’s labour power

ABSTRACT This discussion paper is presented to be read in three simultaneous and different modalities. At one level, it is a historiography of British Bengali women’s labour power and hence an exploration of the historical constraints that vis-a-vis appear as a natural logical consequence but on closer examination performed as part of a broader structure of inequality. At another level, it intervenes, utilising the theoretical lens of Pierre Bourdieu’s ‘thinking tools’ to inform an awareness that does not pathologize, but instead reads against the constructed layers of assumptions to foreground the social conditions that appear as social structures in diminishing Bengali women’s labour power. Finally, the discussion expands the site of analysis, arguing under Sunni orthodoxy based upon the recitation, women have significant labour rights, moreover those rights have diminished in Bangladesh. At the same time, in Britain, social conditions have superseded religious limitations that have benefitted British Bengali women.

Model Predictive Control of Switched Linear Systems With Persistent Dwell-Time Constraints: Recursive Feasibility and Stability

This paper develops a model predictive control (MPC) framework to co-optimize switching sequences and control inputs for switched linear systems subject to persistent dwell-time (PDT) constraints. As a class of time constraints, PDT has been demonstrated to be more general and flexible than others like dwell-time or average dwell-time. Although time constraints are widely used in applications for safety and stability concerns, MPC of switched systems with time constraints often formulates a mixed- integer nonlinear program which cannot obtain the optimal solution in polynomial time, and thus suffers from the loss of recursive feasibility and stability. To address this problem, we propose several novel techniques: (i) the construction of the terminal sets based on two constraint admissible PDT contractive sets, (ii) the introduction of PDT and historical constraints, (iii) the use of two non-globally optimal solutions, and (iv) the prolonged prediction horizon. It is the first time that MPC approaches are applied to the co-optimization problem of switched systems under time constraints with guaranteed recursive feasibility and stability.

What Dynamic Approaches Have Taught Us About Cognition and What They Have Not: On Values in Motion and the Importance of Replicable Forms.

Over the past several decades, research in the cognitive sciences has foregrounded the importance of active bodies and their continuous dependence on the changing environment, strengthening the relevance of dynamical models. These models have been steadily developed within the ecological psychology approach to cognition, which arguably contributes to the "ecological turn" we are witnessing today. The embodied and situated nature of cognition, regarded by some as a passing trend, is presently becoming a largely accepted assumption. In this paper, I claim that in light of these developments, ecological psychology, in alliance with related approaches, such as enactivism and interactivism, has the potential to deeply transform our perspectives on cognition and action, restoring their pertinence to humans as persons. However, an important challenge to the realization of this potential has to be noted: neither the mainstream information-processing approach nor the dynamics-oriented perspective on cognition provides an account of how the capacity of humans to use language and think "symbolically" can be derived from the continuous flow of agent-environment interaction. I will attempt to show that posing the "dynamical" and "computational" hypotheses about the nature of cognition as mutually exclusive approaches to cognition results in undesirable reductionism, which makes it difficult to meet this challenge. There are good reasons, advanced over half a century ago by, for example, Michael Polanyi or Howard Pattee, to think that we need complementary descriptions to understand cognizing systems, in order to grasp the fact that they are governed both by physical laws and by emergent historical constraints. Details of such a complementarity-based approach still await elucidation, but some proposed solutions have the potential to ease the tension between the information-processing and dynamical approaches to cognition and to lead to a better understanding of their interrelation.

Institutional diversity and state-led development: Singapore as a unique variety of capitalism

This paper provides a critique of economic freedom indices through a case study of Singapore's unique political economy. We argue that these metrics reflect an ahistorical approach to development, obscuring real-world institutional diversity. By instantiating a single ideal of laissez-faire and proceeding to measure the magnitude of economic freedom in nations, these indices implicitly treat capitalist varieties as mere defects of laissez-faire rather than as distinct alternatives.Consequently, owing to the discursive power neoliberal metrics enjoy in country-benchmarking, the varied roles that states play are overlooked in development discourse. Singapore's unique political economy and approach to development is one such institutional innovation being neglected. Through its strategic and calibrated control over factor markets, the Singapore state is ranked as a small government by economic freedom indices while simultaneously enjoying significant influence over economic activity. The wider implication is that nations’ unique historical constraints push them onto diverse development trajectories.

Reviving Minjung Theology in the Technological Era: Kim Yong-bok’s Seontopian Zoesophia in dialogue with Theo-Dao

This article explores into Kim Yong-bok’s final reflections on Minjung Theology in dialogue with Theo-Dao, a theology of Dao. Kim’s groundbreaking assertion that Minjung Theology is a sociobiography of Minjung broadens the cosmological Zoegraphy (the narrative of life) beyond historical constraints. It matures into a sapiential Zoesophia (Wisdom of Life), envisioning a Seontopia (East Asian Utopia). Minjung Theology prompts preparation for the impending ultra-technological civilization, characterized by the burgeoning evolution of artificial intelligence, marking a stride toward the future. Kim’s profound insights into Seontopian Zoesophia could serve as foundational pillars for the revival of Minjung Theology in the Anthropocene era of technological civilization. Furthermore, it extends an invitation to future theologians and scholars of religion to perpetuate this line of inquiry.

Crafting Future Memories

Myths of gendered labour and specifically the masculinisation of certain forms of artisanship are bothsteeped in Victorian colonial ideals of female respectability that serve to exclude unemployed, educatedwomen from market relevant, lucrative jobs in carpentry trades, in the city of Lagos, West Africa. Thesehist orically situated dynamics of social exclusion expose an increasing number of educated women topoverty in one of Africa's primary economic hubs. Utilising the linguistic devices of rich descriptionsand first person accounts in this reflective paper, and drawing data from culturally groundedethnographic research on a female carpentry training project in the city, I examine how the communitieswhich emerged from the project negotiate socio economic, familial, and historical constraints in aneffort to buil d new, inclusive training pathways and craft alternative future narratives of gendered labourpractices in Lagos.Keywords

The Limits of Evolutionary Convergence in Sympatry: Reproductive Interference and Historical Constraints Leading to Local Diversity in Warning Traits.

AbstractMutualistic interactions between defended species represent a striking case of evolutionary convergence in sympatry, driven by the increased protection against predators brought by mimicry in warning traits. However, such convergence is often limited: sympatric defended species frequently display different or imperfectly similar warning traits. The phylogenetic distance between sympatric species may indeed prevent evolution toward the exact same signal. Moreover, warning traits are also involved in mate recognition, so trait convergence might result in heterospecific courtship and mating. Here, we develop a mathematical model to investigate the strength and direction of the evolution of warning traits in defended species with different ancestral traits. Specifically, we determine the effect of phenotypic distances between ancestral trait states of sympatric defended species and of the costs of heterospecific sexual interactions on imperfect mimicry and trait divergence. Our analytical results confirm that reproductive interference and historical constraints limit the convergence of warning traits, leading to either complete divergence or imperfect mimicry. Our model reveals that imperfect mimicry evolves only when ancestral trait values differ between species because of historical constraints and highlights the importance of female and predator discrimination in the evolution of such imperfect mimicry. Our study thus provides new predictions on how reproductive interference interacts with historical constraints and may promote the emergence of novel warning traits, enhancing mimetic diversity.

Dispersal syndromes mediate phylogenetic distance decay relationships in a dendritic stream network

AbstractAimUnderstanding the mechanisms underlying the structure and connectivity of ecological communities is a central issue in biogeography. Dispersal syndromes are tightly woven into organisms' life history seen across populations and communities, but measuring dispersal is still complicated in practice. We investigated the role of dispersal syndromes (here, associated with body size, adult flying ability and voltinism) to predict phylogenetic distance decay relationships (DDRs) of aquatic insect assemblages in dendritic stream networks.LocationDu River Basin, China.TaxonAquatic insects (Coleoptera, Diptera, Ephemeroptera, Hemiptera, Lepidoptera, Megaloptera, Odonata, Plecoptera and Trichoptera).MethodsWe applied multiple methods (i.e. deconstruction approach, null models, Mantel tests and partial Mantel tests) to enhance our basic understanding of phylogenetic distance decay patterns. To provide additional insights into correlates of phylogenetic dissimilarity between stream sites, we modelled potential dispersal routes based on overland, watercourse and cost distances.ResultsOverland distances were among the main correlates of phylogenetic distance decay in the stream networks studied, suggesting that aquatic insects disperse overland seeking for habitats suitable for survival and reproduction. However, local environmental filtering was generally more important for phylogenetic DDRs than geographical distances alone. The interaction between environmental vs. dispersal processes in driving spatial patterns of phylogenetic dissimilarity was contingent on different dispersal syndromes. More specifically, significant phylogenetic DDRs were detected only for subsets of large‐bodied, univoltine taxa with strong adult flying abilities, such as dragonflies.Main ConclusionsOverall, historical constraints affect the phylogenetic DDRs in aquatic insects. Dispersal syndromes associated with body size, adult flying ability and voltinism are key features underlying distance decay in phylogenetic assemblage similarity and the evolutionary legacies of aquatic insects in dendritic stream networks.

Beyond the Ideal: Anne Brontë's Realistic Feminism

This article offers a fresh perspective on Anne Brontë's feminist stance in her novels The Tenant of Wildfell Hall and Agnes Grey. While previous scholars have criticized Brontë's portrayal of her female protagonists in a manner that contradicts her feminist message, this article argues that Brontë's nuanced portrayal of the complexities of female subjectivity within the social, cultural, and historical constraints of her time is essential to her feminist stance. Anne Brontë empowers her female characters with realistic feminine tools to cope with the patriarchal suppression they face and calls for a rethinking of the miserable situation of women in the Victorian patriarchal society. The article argues that Brontë's aim is not to call for an impossible revolution through an ideal feminine figure but rather to promote action based on the reality of the situation. This article's originality lies in its fresh and sophisticated interpretation of Brontë's feminist stance that avoids reducing her characters to mere symbols of resistance and acknowledges the complexities of female subjectivity in a patriarchal society.

Osteoradionecrosis rate in oropharynx cancer treated with dose volume histogram based constraints

ObjectivesMandibular dose constraints are designed to limit high dose to small volumes to avoid osteoradionecrosis (ORN). Based upon a published experience, intermediate-dose constraints were introduced but have not been independently validated. We hypothesize that these constraints lower ORN rate without compromising other organs at risk (OAR). MethodsOropharyngeal cancer patients treated with standard fractionation adjuvant/definitive VMAT from 01/2014–08/2020 were included. In 09/2017, mandibular dose constraint was changed from historical constraint (HC) of D 0.1 cc < 70 Gy to modified constraints (MC) of V 44 Gy < 42%, V 58 Gy < 25%, D 0.5 cc < 70 Gy. OAR dosimetric changes and ORN development were evaluated. Regression modelling predicted long-term ORN cases in MC group. ResultsThere were 174 patients, 71 in MC group. Seven cases of ORN in HC group at a median follow up (FU) of 39 months and 1 case of ORN in MC group at a median FU of 11 months were observed. More patients in the MC group met V 44 Gy (87% vs 62%, p < 0.01) and V 58 Gy constraints (92% vs 73%, p < 0.01). Mean doses to OARs did not rise. Mandible V 44 Gy and V 58 Gy were significantly associated with ORN (p < 0.01 and p = 0.03, respectively) across all patients. In the HC group, V 44 Gy was independently associated with ORN (p = 0.01). To account for shorter FU in MC group, logistic regression of ORN based on V 44 Gy in HC patients was performed. This predicts 3.2 ORN cases in the MC group (95% CI: 0.00–6.4). ConclusionAchieving V 44 Gy and V 58 Gy was successful in 87% of cases without sacrificing target coverage or OARs and resulted in non-significant ORN decrease.