Concurrent analysis of choice and control in childbirth?

Background: this paper reports original research on choice and control in childbirth. Eight women were interviewed as part of a wider investigation into locus of control in women with pre-labour rupture of membranes at term (PROM) [1].Methods: the following study uses concurrent analysis to sample and analyse narrative aspects of relevant literature along with these interviews in order to synthesise a generalisable analysis of the pertinent issues. The original PROM study had found that women experienced a higher degree of control in hospital, a finding that appeared at odds with contemporary notions of choice. However, this paper contextualises this finding by presenting narratives that lucidly subscribe to the dominant discourse of hospital as the safest place to give birth, under the premise of assuring a live healthy baby irrespective of their management type.Results: this complex narrative is composed of the following themes: 'perceiving risk', 'being prepared', 'reflecting on experience', maintaining control' and relinquishing control'. These themes are constructed within and around the medical, foetocentric, risk averse cultural context. Primary data are presented throughout to show the origins and interconnected nature of these themes.Conclusions: within this context it is clear that there is a highly valued role for competent health professionals that respect, understand and are capable of facilitating genuine choice for women

Journeyman's stage: Rehistoricizing O'Neill, his audience, and the American family in the 1920s

The years between 1921 and 1934 were Eugene O'Neill's journeyman years, a time when the country's theatrical community, hungering after a national playwright, turned a spotlight on a good writer in hopes of finding a great one. The discursive interplay between the maturing playwright and his growing constituency--ardently supportive critics, equally passionate detractors, and a widening audience both in numbers and social classes--shaped both the young playwright and a burgeoning national art.After the manner of the New Historicism, I examine how the American theatre reproduces specific cultural values through the representations of the American family on stage. The First Man (1922), Desire Under the Elms (1924), and Strange Interlude (1928) enact and debate revisionary family structures. Through conflicts over obstacles to reproduction, who will control reproduction, and what form the next generation will take, these plays challenge the status quo of the "traditional" American family in the 1920s. O'Neill's audiences responded vigorously to these conflicts--rejecting the unspeakably intimate (First Man), censoring the aggressively new (Desire), and fanatically embracing a therapeutic experience (Interlude).Through the vehicle of vested theatre audiences, these journeyman plays disseminated familial trends and participated in social change. Familial revisions intersect with a number of 1920s historical trends: the politics of obstetrics in the 1920s, pop anthropology, the popularization of Freud, sensational child murders (including the 1925 Leopold and Loeb trial), eugenics crusades, the legacies of Puritanism, and revisionary theologies (including Interlude's innovative mother-centered theology which parallels early revisionary Freudians like Melanie Klein).My work focuses on the interplay between staged family conflicts and extra-literary cultural evolution. I examine newspaper reviews and other historical discourse (including a detailed analysis of the 1925 campaign to censor Desire Under the Elms) in order to discover why some of the plays' family structures were received with favor by audiences or critics, while others triggered controversy. This analysis demonstrates how the colloquy between stage and audience affected O'Neill's development and his audiences' attitudes toward their would-be national playwright.U of I OnlyETDs are only available to UIUC Users without author permissio

Multiparametric assessment of mitochondrial respiratory inhibition in HepG2 and RPTEC/TERT1 cells using a panel of mitochondrial targeting agrochemicals

Evidence is mounting for the central role of mitochondrial dysfunction in several pathologies including metabolic diseases, accelerated ageing, neurodegenerative diseases and in certain xenobiotic-induced organ toxicity. Assessing mitochondrial perturbations is not trivial and the outcomes of such investigations are dependent on the cell types used and assays employed. Here we systematically investigated the effect of electron transport chain (ETC) inhibitors on multiple mitochondrial-related parameters in two human cell types, HepG2 and RPTEC/TERT1. Cells were exposed to a broad range of concentrations of 20 ETC-inhibiting agrochemicals and capsaicin, consisting of inhibitors of NADH dehydrogenase (Complex I, CI), succinate dehydrogenase (Complex II, CII) and cytochrome bc1 complex (Complex III, CIII). A battery of tests was utilised, including viability assays, lactate production, mitochondrial membrane potential (MMP) and the Seahorse bioanalyser, which simultaneously measures extracellular acidification rate [ECAR] and oxygen consumption rate [OCR]. CI inhibitors caused a potent decrease in OCR, decreased mitochondrial membrane potential, increased ECAR and increased lactate production in both cell types. Twenty-fourhour exposure to CI inhibitors decreased viability of RPTEC/TERT1 cells and 3D spheroid-cultured HepG2 cells in the presence of glucose. CI inhibitors decreased 2D HepG2 viability only in the absence of glucose. CII inhibitors had no notable effects in intact cells up to 10 µM. CIII inhibitors had similar effects to the CI inhibitors. Antimycin A was the most potent CIII inhibitor, with activity in the nanomolar range. The proposed CIII inhibitor cyazofamid demonstrated a mitochondrial uncoupling signal in both cell types. The study presents a comprehensive example of a mitochondrial assessment workflow and establishes measurable key events of ETC inhibition.publishe

Triboluminescence from Pharmaceutical Formulations

Triboluminescence (TL) is shown to enable selective detection of trace crystallinity within nominally amorphous solid dispersions (ASDs). ASDs are increasingly used for the preparation of pharmaceutical formulations, the physical stability of which can be negatively impacted by trace crystallinity introduced during manufacturing or storage. In the present study, TL measurements of a model ASD consisting of griseofulvin in polyethylene glycol produced limits of detection of 140 ppm. Separate studies of the particle size dependence of sucrose crystals and the dependence on polymorphism in clopidogrel bisulfate particles are both consistent with a mechanism for TL closely linked to the piezoelectric response of the crystalline fraction. Whereas disordered polymeric materials cannot support piezoelectric activity, molecular crystals produced from homochiral molecules adopt crystal structures that are overwhelmingly symmetry-allowed for piezoelectricity. Consequently, TL may provide a broadly applicable and simple experimental route for sensitive detection of trace crystallinity within nominally amorphous materials

New approach methods (NAMs) supporting read-across: Two neurotoxicity AOP-based IATA case studies

Read-across approaches are considered key in moving away from in vivo animal testing towards addressing data-gaps using new approach methods (NAMs). Ample successful examples are still required to substantiate this strategy. Here we present and discuss the learnings from two OECD IATA endorsed read-across case studies. They involve two classes of pesticides – rotenoids and strobilurins – each having a defined mode-of-action that is assessed for its neurological hazard by means of an AOP-based testing strategy coupled to toxicokinetic simulations of human tissue concentrations. The endpoint in question is potential mitochondrial respiratory chain mediated neurotoxicity, specifically through inhibition of complex I or III. An AOP linking inhibition of mitochondrial respiratory chain complex I to the degeneration of dopaminergic neurons formed the basis for both cases but was deployed in two different regulatory contexts. The two cases also exemplify several different read-across concepts: analogue versus category approach, consolidated versus putative AOP, positive versus negative prediction (i.e., neurotoxicity versus low potential for neurotoxicity), and structural versus biological similarity. We applied a range of NAMs to explore the toxicodynamic properties of the compounds, e.g., in silico docking as well as in vitro assays and readouts – including transcriptomics – in various cell systems, all anchored to the relevant AOPs. Interestingly, although some of the data addressing certain elements of the read-across were associated with high uncertainty, their impact on the overall read-across conclusion remained limited. Coupled to the elaborate regulatory review that the two cases underwent, we propose some generic learnings of AOP-based testing strategies supporting read-across.This work was supported by the European Union’s Horizon 2020 research and innovation programme under grant agreement no. 681002 (EU-ToxRisk). Parts of this work contributed to two IATA Case Studies Projects “Identification and characterization of parkinsonian hazard liability of deguelin by an AOP-based testing and read across approach” and “Mitochondrial complex-III-mediated neurotoxicity of azoxystrobin – Read-across to other strobilurins” (van der Stel et al., 2020b; Bennekou et al., 2020)