Broad Changes Research Articles

Defining a cohort of anemia-activated cis elements reveals a mechanism promoting erythroid precursor function

AbstractAcute anemia elicits broad transcriptional changes in erythroid progenitors and precursors. We previously discovered a cis-regulatory transcriptional enhancer at the sterile alpha motif domain-14 enhancer locus (S14E), defined by a CANNTG-spacer-AGATAA composite motif and occupied by GATA1 and TAL1 transcription factors, is required for survival in severe anemia. However, S14E is only 1 of dozens of anemia-activated genes containing similar motifs. In a mouse model of acute anemia, we identified populations of expanding erythroid precursors, which increased expression of genes that contain S14E-like cis elements. We reveal that several S14E-like cis elements provide important transcriptional control of newly identified anemia-inducing genes, including the Ssx-2 interacting protein (Ssx2ip). Ssx2ip expression was determined to play an important role in erythroid progenitor/precursor cell activities, cell cycle regulation, and cell proliferation. Over a weeklong course of acute anemia recovery, we observed that erythroid gene activation mediated by S14E-like cis elements occurs during a phase coincident with low hematocrit and high progenitor activities, with distinct transcriptional programs activated at earlier and later time points. Our results define a genome-wide mechanism in which S14E-like enhancers control transcriptional responses during erythroid regeneration. These findings provide a framework to understand anemia-specific transcriptional mechanisms, ineffective erythropoiesis, anemia recovery, and phenotypic variability within human populations.

Changes in Obstetrical Practices and Pregnancy Outcomes Following the ARRIVE Trial

(Am J Obstet Gynecol. 2022;226:716.e1–716.e12) As cesarean delivery rates approach an all-time high in the United States and other developed countries, mothers and neonates are at increased risk for morbidities associated with this mode of birth. Data from the 2018 ARRIVE (A Randomized Trial of Induction Versus Expectant Management) trial showed a decrease in cesarean delivery rates and hypertensive disorders when obstetric practices shifted to prioritize induction for 39-week, low-risk, singleton, nulliparous births. Further, meta-analysis demonstrated 39-week inductions lower the risk of infection in the peripartum period, result in fewer NICU (neonatal intensive care unit) admissions and lessen perinatal mortality. As there is a well acknowledged “evidence-to-practice” gap it is not well understood if there has been wide-spread clinical uptake of the recommendation for obstetricians to offer induction to low-risk nulliparous women at 39 weeks. The question of broad change in obstetrical practice and perinatal outcomes following the ARRIVE trial is investigated.

Repertoires of citizen action in hybrid settings

AbstractMotivationIn recent years, a growing literature has emerged analysing how organized citizen action can achieve more accountable and inclusive governance. While this literature is mostly focused on relatively open, democratic, or more stable contexts, often in western democracies, only a small proportion of the world's population lives in such settings. Rather, authoritarianism is growing and democratic spaces are closing globally.PurposeThis article explores how hybrid political settings—those which have both democratic and non‐democratic features, fragmented authority, and closing civic space—affect strategies of citizen action.Methods and approachDrawing from a large number of single and comparative case studies of citizen action, mainly from Mozambique, Myanmar, Nigeria, and Pakistan, the article builds on work by Tilly and Tarrow on repertoires of contention. Based on these, the article develops a typology of eight repertoires of citizen action through which citizens may express their grievances and attempt to hold authorities to account.FindingsThe literature suggests that there may be little space for contentious social and political action in closed or authoritarian settings. This article finds, however, that a rich and diverse tapestry of citizen action may be seen in the “hybrid” settings (those which have both democratic and non‐democratic features). Shaped by political opportunities as well as by key trigger events, these repertoires will vary according to their visibility and their level of “ruliness” and may shift or re‐enforce one another over time, contributing to building blocks for broader accountability and democratic governance.Policy implicationsPolicy and donor interventions aimed at supporting citizen‐led action for accountability have often focused on the most visible and ruly of these strategies. However, we find that the more hidden or more unruly forms of action are important in and of themselves and help to create building blocks for broader changes. For those who are interested in supporting citizen‐led accountability, mapping these broader repertoires will be important to understand the full range of accountability strategies available, going beyond more commonly understood approaches.

Characterization of ctDNA findings at the end of life in patients with prostate cancer.

230 Background: Somatic alterations change over time in response to treatment and disease progression in patients with prostate cancer (PCa). We report ctDNA findings of patients who died from PCa within 3 months of a ctDNA assessment to better characterize patients with fatal disease. Methods: A total of 118 patients with PCa specific mortality who had been treated at Tulane Cancer Center and had ctDNA assessments between 2015 and 2022. The ctDNA was assessed by Guardant360 (Guardent Health, Inc) assays to identify alterations, pathogenic mutations and/or copy number alterations (CNAs) in cancer-related genes. Clinical annotation including treatment history, genetics, and staging were also obtained. Statistical analyses included Fischer’s Exact and Wilcoxon tests. Results: Of the 118 patients with PCa specific mortality, 42% (49/118) had a ctDNA assessment <3 months from death. Of 49 CRPC patients tested within 3 months of death, the median number of life extending therapies (LET) at death was 5 (2-9). Patients had a median of 2 (0-6) LET prior to first ctDNA screening and 3 (0-7) LET in between first and last ctDNA assessment. Of the total gene alterations detected on ctDNA analysis, within 3 months of death, the most common alterations detected were 65.3% (32/49) TP53, 44.9% (22/49) AR, 28.6% (14/49) EGFR, 24.5% (12/49) PIK3CA, 22.4% (11/49) MYC, and 20.4% (10/49) CDK6. In a paired analysis(n= 45) of first and last ctDNA screening, AR (OR= 2.35, 95% C.I. (0.99, 5.62), p= 0.05), CDK6 (OR= 4.00, 95% C.I. (1.02, 15.68), p= 0.04), FGFR1 (OR= 9.51, 95% C.I. (1.14, 79.61), p= 0.03), and EGFR (OR= 9.71, 95% C.I. (2.06, 45.83), p= 0.0009) were significantly more likely to be detected in ctDNA screening within 3 months of death. In addition, ctDNA alterations in general were significantly more likely to be detected at the end-of-life (p=< 0.00001). Other ctDNA gene mutations did not have statistically significant increases. Conclusions: An analysis of patients with PCa mortality showed most frequent gene alterations in TP53, AR, EGFR, PIK3CA, MYC, and CDK6. When comparing patients’ first and last ctDNA, alterations were significantly more likely by time of death in AR, CDK6, EGFR, FGFR and there was a significant increase in overall detection of somatic alterations in ctDNA. These analyses are limited to the genes assessed on the ctDNA panel and may or may not reflect all of the functionally relevant alterations. Further the CNAs reported herein may reflect broad genomic changes rather than specific gene alterations.

Could an incumbent firm develop a radically new medical technology with an old organizational capability?

ABSTRACT Our case study addresses how an incumbent firm from the pharmaceutical industry develops a radically new medical technology. We engage with the question as to whether such a radical innovation could be developed by relying on existent patterns of actions (existing organisational capability) or whether such novelty also requires doing innovation differently (new organisational capability). We argue that a sharp conceptual distiction between sustaining existent and developing new organizational capabilities is inadequate for describing organization of a radical innovation within an incubent firm. We propose that developing a radical innovation in a nascent innovation ecosystem requires multiple modifications across many systemic processes that constitute organisational capability for innovation. Hence, many small and interdependent innovations in organisational processes, practices and structures can make a big difference for developing radically new technology. Radical technological innovation goes hand in hand with management innovation. We argue that the nascent innovation ecosystem necessitates a careful balancing between legitimacy-seeking and advantage-seeking actions, which guides managers when adapting organisational capability for innovation. When complexity of an innovation ecosystem increases, broader changes across multiple systemic processes for innovation are required. A degree of continuity between existing and new organisational capabilities for innovation increases the internal acceptance of radical innovation.

The transition from an Indigenous to a European influenced fire regime at Lake Werri Berri, south-east Australia

The drivers of fire regimes prior to the European occupation of Australia are still contentious, with some advocating regimes dominated by anthropogenic ignitions and others advocating a climate source or mixture of these elements. Here, we examine an 850-year history of fire regimes at Lake Werri Berri in south-east Australia, prior to and following European occupation. Macroscopic charcoal and FTIR spectroscopy were used to infer broad changes of the fire regime in proximity to the lake. We found little change through much of the 850-year period and most interesting, no apparent change following the initial displacement of Indigenous peoples and the introduction of farming and woodcutting to the region by Europeans. From the mid-20th Century onwards, there was an increase in both area burnt and fire severity or intensity, likely the result of increased fuel load and connectivity following an extended period of increased precipitation and heavier recreational land usage, which likely led to an increase in anthropogenic ignitions.

National Digital Infrastructure and India’s Healthcare Sector: Physician’s Perspectives

Patient-centric digital infrastructure can potentially enhance the efficiency of healthcare systems. However, even in developed nations, evidence suggests low adoption rates for such infrastructure and lack of support from clinicians is considered as one of the most critical hindering factors. In this study, we examine physicians' perceptions of the proposed large-scale information technology initiative in India that aims to transform the health sector and provide universal health coverage to all residents of India. We employed the information ecology lens to understand the broader changes in the healthcare system that could result from the initiative. We use focus group discussion and in-depth interviews to comprehend the perceptions of doctors about the initiative. Drawing upon Foucault’s conceptualization of power, we find that physicians, the key stakeholders in this initiative, are skeptical about the changes in the locus of power in the new ecosystem. Specifically, they perceive that knowledge power has shifted from a historical “expert knowledge power” to power related to “data management.” The physicians believe that changes are expected to manifest through monitoring, controlling, and managing the data rather than providing knowledge-based services. We present recommendations to engage physicians' perspectives in implementing large-scale patient-centric digital infrastructure.

Cryptocurrency regulation and market quality

We examine the effects of the 2021 Chinese cryptocurrency ban on several aspects of crypto market quality, namely, prices, volatility, and liquidity. We find that average crypto prices plunge and liquidity deteriorates, while volatility spikes in response to the announcement of the ban. While the volatility surge is short-lived, the fall in crypto values and liquidity persists. The results are robust across dollar trading volume sorts, and remain significant after taking into account the inter-connectedness between the market quality measures in a vector autoregressive framework. We present the results in comparison with the 2017 Chinese cryptocurrency ban, which did not result in the same broad changes in the crypto market. We also discuss the potential household ownership and environmental implications of the ban.

Evaluating response mechanisms of soil microbiomes and metabolomes to Bt toxin additions

The accumulation and persistence of Bt toxins in soils from Bt plants and Bt biopesticides may result in environmental hazards such as adverse impacts on soil microorganisms. However, the dynamic relationships among exogenous Bt toxins, soil characteristics, and soil microorganisms are not well understood. Cry1Ab is one of the most commonly used Bt toxins and was added to soils in this study to evaluate subsequent changes in soil physiochemical properties, microbial taxa, microbial functional genes, and metabolites profiles via 16S rRNA gene pyrosequencing, high-throughput qPCR, metagenomic shotgun sequencing, and untargeted metabolomics. Higher additions of Bt toxins led to higher concentrations of soil organic matter (SOM), ammonium (NH+4-N), and nitrite (NO2--N) compared against controls without addition after 100 days of soil incubation. High-throughput qPCR analysis and shotgun metagenomic sequencing analysis revealed that the 500 ng/g Bt toxin addition significantly affected profiles of soil microbial functional genes involved in soil carbon (C), nitrogen (N), and phosphorus (P) cycling after 100 days of incubation. Furthermore, combined metagenomic and metabolomic analyses indicated that the 500 ng/g Bt toxin addition significantly altered low molecular weight metabolite profiles of soils. Importantly, some of these altered metabolites are involved in soil nutrient cycling, and robust associations were identified among differentially abundant metabolites and microorganisms due to Bt toxin addition treatments. Taken together, these results suggest that higher levels of Bt toxin addition can alter soil nutrients, probably by affecting the activities of Bt toxin-degrading microorganisms. These dynamics would then activate other microorganisms involved in nutrient cycling, finally leading to broad changes in metabolite profiles. Notably, the addition of Bt toxins did not cause the accumulation of potential microbial pathogens in soils, nor did it adversely affect the diversity and stability of microbial communities. This study provides new insights into the putative mechanistic associations among Bt toxins, soil characteristics, and microorganisms, providing new understanding into the ecological impacts of Bt toxins on soil ecosystems.

Arsenic Exposure Causes Global Changes in the Metalloproteome of Escherichia coli.

Arsenic is a toxic metalloid with differential biological effects, depending on speciation and concentration. Trivalent arsenic (arsenite, AsIII) is more toxic at lower concentrations than the pentavalent form (arsenate, AsV). In E. coli, the proteins encoded by the arsRBC operon are the major arsenic detoxification mechanism. Our previous transcriptional analyses indicate broad changes in metal uptake and regulation upon arsenic exposure. Currently, it is not known how arsenic exposure impacts the cellular distribution of other metals. This study examines the metalloproteome of E. coli strains with and without the arsRBC operon in response to sublethal doses of AsIII and AsV. Size exclusion chromatography coupled with inductively coupled plasma mass spectrometry (SEC-ICPMS) was used to investigate the distribution of five metals (56Fe, 24Mg, 66Zn, 75As, and 63Cu) in proteins and protein complexes under native conditions. Parallel analysis by SEC-UV-Vis spectroscopy monitored the presence of protein cofactors. Together, these data reveal global changes in the metalloproteome, proteome, protein cofactors, and soluble intracellular metal pools in response to arsenic stress in E. coli. This work brings to light one outcome of metal exposure and suggests that metal toxicity on the cellular level arises from direct and indirect effects.

Review: Dreams of Flight: The Great Escape in American Film Culture, by Dana Polan

Review: <i>Dreams of Flight:</i> The Great Escape <i>in American Film Culture</i>, by Dana Polan

Preaching to the choir: effects of the Mentors in Violence Prevention programme on ‘the bad apples’

Mentors in Violence Prevention (MVP) is a systematic education programme aimed at addressing gender inequality and preventing violence among boys and men. The programme originates from Canada and the USA, and since 2015 has been introduced in a number of Swedish schools. Whereas most evaluations of MVP and other programmes addressing gender-based violence focus on broad changes, we argue that these evaluations fail to provide insight into where and for whom the programmes are or are not effective. By identifying the participants with knowledge and attitudes furthest away from the target assumptions of the programme and following them throughout the programme, we can see what effects the programme has on those with the most problematic knowledge and attitudes. The study shows that MVP does not seem to contribute to a more positive development for the group of students whose knowledge and attitudes are furthest from the programme’s target assumptions. Moreover, the study shows that the comparison group shows a more positive development over time than the MVP group. This leads to the conclusion that MVP seems to have limited potential to change the specific group with low levels of knowledge about violence and most problematic attitudes towards violent behaviour.

Study examines challenges facing ER staff with BH patients

Observing the challenges and care dynamics experienced by emergency room (ER) nurses and physicians caring for patients with mental health and substance use disorders (SUDs), who noted that these patient populations are typically time‐ and energy‐intensive, researchers of a new study on ER staff acknowledge that broad public and institutional changes are needed to deliver better ER care for behavioral health patients. The study is considered the largest qualitative study on this issue conducted with physicians and nurses, they stated.

AAV-based gene therapy prevents and halts the progression of dilated cardiomyopathy in a mouse model of phosphoglucomutase 1 deficiency (PGM1-CDG)

Phosphoglucomutase 1 (PGM1) deficiency is recognized as the third most common N-linked congenital disorders of glycosylation (CDG) in humans. Affected individuals present with liver, musculoskeletal, endocrine, and coagulation symptoms; however, the most life-threatening complication is the early onset of dilated cardiomyopathy (DCM). Recently, we discovered that oral D-galactose supplementation improved liver disease, endocrine, and coagulation abnormalities, but does not alleviate the fatal cardiomyopathy and the associated myopathy. Here we report on left ventricular ejection fraction (LVEF) in 6 individuals with PGM1-CDG. LVEF was pathologically low in most of these individuals and varied between 10% and 65%. To study the pathobiology of the cardiac disease observed in PGM1-CDG, we constructed a novel cardiomyocyte-specific conditional Pgm2 gene (mouse ortholog of human PGM1) knockout (Pgm2 cKO) mouse model. Echocardiography studies corroborated a DCM phenotype with significantly reduced ejection fraction and left ventricular dilation similar to those seen in individuals with PGM1-CDG. Histological studies demonstrated excess glycogen accumulation and fibrosis, while ultrastructural analysis revealed Z-disk disarray and swollen/fragmented mitochondria, which was similar to the ultrastructural pathology in the cardiac explant of an individual with PGM1-CDG. In addition, we found decreased mitochondrial function in the heart of KO mice. Transcriptomic analysis of hearts from mutant mice demonstrated a gene signature of DCM. Although proteomics revealed only mild changes in global protein expression in left ventricular tissue of mutant mice, a glycoproteomic analysis unveiled broad glycosylation changes with significant alterations in sarcolemmal proteins including different subunits of laminin-211, which was confirmed by immunoblot analyses. Finally, augmentation of PGM1 in KO mice via AAV9-PGM1 gene replacement therapy prevented and halted the progression of the DCM phenotype.

Metabolic reprogramming underlies cavefish muscular endurance despite loss of muscle mass and contractility

Physical inactivity is a scourge to human health, promoting metabolic disease and muscle wasting. Interestingly, multiple ecological niches have relaxed investment into physical activity, providing an evolutionary perspective into the effect of adaptive physical inactivity on tissue homeostasis. One such example, the Mexican cavefish Astyanax mexicanus, has lost moderate-to-vigorous activity following cave colonization, reaching basal swim speeds ~3.7-fold slower than their river-dwelling counterpart. This change in behavior is accompanied by a marked shift in body composition, decreasing total muscle mass and increasing fat mass. This shift persisted at the single muscle fiber level via increased lipid and sugar accumulation at the expense of myofibrillar volume. Transcriptomic analysis of laboratory-reared and wild-caught cavefish indicated that this shift is driven by increased expression of pparγ-the master regulator of adipogenesis-with a simultaneous decrease in fast myosin heavy chain expression. Exvivo and invivo analysis confirmed that these investment strategies come with a functional trade-off, decreasing cavefish muscle fiber shortening velocity, time to maximal force, and ultimately maximal swimming speed. Despite this, cavefish displayed a striking degree of muscular endurance, reaching maximal swim speeds ~3.5-fold faster than their basal swim speeds. Multi-omic analysis suggested metabolic reprogramming, specifically phosphorylation of Pgm1-Threonine 19, as a key component enhancing cavefish glycogen metabolism and sustained muscle contraction. Collectively, we reveal broad skeletal muscle changes following cave colonization, displaying an adaptive skeletal muscle phenotype reminiscent to mammalian disuse and high-fat models while simultaneously maintaining a unique capacity for sustained muscle contraction via enhanced glycogen metabolism.

Assessing the Effects of Exercise, Cognitive Demand, and Rest on Audiovisual Multisensory Processing in OlderAdults: A Pilot Study.

A single bout of aerobic exercise is related to positive changes in higher-order cognitive function among older adults; however, the impact of aerobic exercise on multisensory processing remains unclear. Here we assessed the effects of a single bout of aerobic exercise on commonly utilized tasks that measure audiovisual multisensory processing: response time (RT), simultaneity judgements (SJ), and temporal-order judgements (TOJ), in a pilot study. To our knowledge this is the first effort to investigate the effects of three well-controlled intervention conditions on multisensory processing: resting, completing a cognitively demanding task, and performing aerobic exercise for 20 minutes. Our results indicate that the window of time within which stimuli from different modalities are integrated and perceived as simultaneous (temporal binding window; TBW) is malleable and changes after each intervention condition for both the SJ and TOJ tasks. Specifically, the TBW consistently became narrower post exercise while consistently increasing in width post rest, suggesting that aerobic exercise may improve temporal perception precision via broad neural change rather than targeting the specific networks that subserve either the SJ or TOJ tasks individually. The results from the RT task further support our findings of malleability of the multisensory processing system, as changes in performance, as assessed through cumulative probability models, were observed after each intervention condition. An increase in integration (i.e., greater magnitude of multisensory effect) however, was only found after a single bout of aerobic exercise. Overall, our results indicate that exercise uniquely affects the central nervous system and may broadly affect multisensory processing.

Pathways to Suicide among Police in Rajasthan: Perceptions and Experiences of Police Personnel.

Background: Evidence regarding the experience and perceptions of police personnel with suicide in South Asia is limited. This study explored the lived experiences and perceptions of suicide among police personnel in an Indian state. The focus was on explanations of and reasons for suicide. Methods: We conducted 20 qualitative interviews in 2021 with police of different ranks, guided by a topic guide. The reflexive thematic analysis approach was supported by the use of NVivo 12, a qualitative software package. Results: We explore three intersecting key themes around suicide in the police force, including: (1) the stressful police environment; (2) expectations of mental strength; and (3) police image and help-seeking. We discuss the tensions between these themes and how to address the challenges of supporting police personnel. Conclusions: To support and improve police personnel's mental well-being training and support are needed but also broader changes at the organisational level. These need to take social and historical factors into account. An increased level of suicide and mental health literacy will not only benefit the police force but also the general public, and it would be very timely with recent changes in the Indian mental health and suicide policy context.

Abstract B023: Oncostatin M induces HIF1A-dependent collective cell migration in mammary epithelial cells

Abstract Over 40,000 deaths due to breast cancer occur annually in the United States, and metastatic status is the most important determinant in prognosis. The metastatic potential of cancer cells is strongly influenced by interactions with the tumor microenvironment, which are mediated in large part by growth factors and cytokines that can modulate cellular phenotype. One such ligand is Oncostatin M (OSM), a cytokine produced by macrophages in breast cancer tumors. An emerging body of literature suggests that OSM is capable of shifting cancer cells into a metastatic cell state, however the mechanistic relationship between OSM signaling and cancer progression remains unclear. Gaining a better understanding of the molecular and microenvironmental factors that promote metastasis is critical for design of therapeutic strategies that can mitigate metastasis for patients with breast cancer. In previous studies, we found that MCF10A mammary epithelial cells exposed to OSM form multicellular clusters that migrate collectively, a process termed collective cell migration (CCM). This migratory phenotype has been linked to an increase in metastatic potential in breast cancer and provides an explanation for the association between OSM and cancer progression. Understanding the mechanism that underlies OSM-induced CCM may reveal how this phenotype contributes to metastasis. Toward this goal, we performed RNAseq and proteomic profiling of OSM-treated MCF10A cells, which revealed broad changes in molecular activity. Notably, OSM induced upregulation of transcription factors associated with migration (e.g., CEBPB, HIF1A) as well as a set of transcripts that contribute to cell junction formation (e.g., CDH3, GJA1). Network analysis revealed key nodes that may be associated with the phenotypic response, and functional screening with siRNA knock-down identified HIF1A as an essential mediator of OSM-induced CCM. Cellular activation of HIF1A is typically observed in response to hypoxia, a microenvironmental condition commonly found in human breast tumors, and patients with increased HIF1A expression have been found to be at a greater risk of metastasis. Our findings suggest that OSM released from tumor infiltrating myeloid cells may offer an alternative hypoxia-independent pathway to induce tumor cell upregulation of HIF1A and activation of metastatic cascades. Single-cell RNA-seq will be utilized to identify the transcriptional programs regulated by HIF1A in OSM-treated MCF10A cells. To further explore this hypothesis, we have performed additional experiments investigating the HIF1A signaling axis using organoids derived from MMTV-PyMT mice, cultured ex vivo in collagen gels. Initial results indicate that exposure to OSM increase cancer cell invasion in this mouse model of breast cancer. Future experiments will explore the relationship between HIF1A activation and MMTV-PyMT invasion and dissemination. Collectively, these results demonstrate an important connection between OSM, HIF1A, and CCM and help clarify the signaling consequences of OSM on cancer cell invasion. Citation Format: Ian C. McLean. Oncostatin M induces HIF1A-dependent collective cell migration in mammary epithelial cells [abstract]. In: Proceedings of the AACR Special Conference: Cancer Metastasis; 2022 Nov 14-17; Portland, OR. Philadelphia (PA): AACR; Cancer Res 2022;83(2 Suppl_2):Abstract nr B023.

Perceptions and experiences of environmental health and risks among Latina mothers in urban Los Angeles, California, USA

BackgroundEnvironmental exposures during pregnancy and early childhood can have acute and chronic adverse health impacts. As minoritized populations are more likely to reside in areas with greater pollution, it is important to understand their views and lived experiences to inform action. The purpose of this community-driven qualitative research study was to understand how urban Latina mothers in Los Angeles County, California perceived environmental health and risks.MethodsWe conducted semi-structured individual interviews with Latina pregnant women and mothers of young children, recruited through existing collaborations with community organizations. Interviews conducted in either English or Spanish and were coded inductively according to a modified grounded theory approach.ResultsThirty-six Latina mothers completed interviews between August–October 2016. Participants lived primarily in low-income communities of South-Central Los Angeles and East Los Angeles. We identified three major themes based on the participants’ responses during interviews: Defining the Environment, Environment & Health Risks, and Social & Political Responsibility. Women defined their environment in terms of both “nature” and “hazards.” They consistently identified foul odors, dirtiness, noise, trash, bugs, smoke, and other visible blights as indicators of household and neighborhood environmental hazards. They expressed fear and uncertainty about how their environment could affect their health and that of their children, as well as specific concerns about respiratory health, asthma, allergies, cancer, and adverse pregnancy outcomes. Mothers often changed individual behaviors around diet and cleaning during pregnancy but were frustrated by power imbalances that left them unable to change their home or neighborhood environments, despite their desire to do so.DiscussionOur study is among the first to describe how urban Latina mothers perceive and experience environmental health risks during pregnancy and early childhood. Our research suggests additional attention is needed by public health professionals and researchers to address the environmental health risks that matter most to urban Latina mothers. They also highlight the tension that many urban Latina mothers feel between wanting to protect their families’ health and well-being and feeling powerless to change their environment. Broad policy changes, rather than additional individual recommendations, are needed to address the concerns of this vulnerable population.

The role of temple institutions in Wari imperial expansion at Pakaytambo, Peru

During the Andean Middle Horizon (CE 600–1000), the highland Wari emerged as an expansive power that formed the largest pre-Inka imperial project in the Andes. Although territorially discontinuous, the introduction of Wari state institutions to disparate regions of Peru knit together far-flung and diverse social groups. Recent excavations at Pakaytambo in southern Peru have uncovered a Wari ritual complex replete with a d-shaped temple, patio-group architecture, and monumental platform construction. The complex was established in the upper Majes-Chuquibamba drainage of Arequipa at ∼ 1700 masl and was strategically placed along a major pre-Inka road at the nexus of highland-coastal populations and socio-ecological zones. In this article, excavations at Pakaytambo are presented and discussed in terms of architectural canons, site chronology, and material studies in consideration to broader changes during the late Middle Horizon. d-shaped temples represent the most ubiquitous form of civic-ceremonial architecture related to Wari religious institutions and imperial ideology. Thus, Pakaytambo provides invaluable insights into the production of state authority through public ritual and performance in regions beyond a state heartland. A focus on institutions, their group members, norms, shared objectives, and archaeological patterning provides a middle-level unit of social analysis complimentary to high theory of the state.