Polyoxazoline-Based Bottlebrush and Brush-Arm Star Polymers via ROMP: Syntheses and Applications as Organic Radical Contrast Agents

Copyright © 2019 American Chemical Society. The synthesis of functional poly(2-alkyl-2-oxazoline) (PAOx) copolymers with complex nanoarchitectures using a graft-through ring-opening metathesis polymerization (ROMP) approach is described. First, well-defined norbornene-terminated poly(2-ethyl-2-oxazoline) (PEtOx) macromonomers (MM) were prepared by cationic ring-opening polymerization. ROMP of these MMs produced bottlebrush copolymers with PEtOx side chains. In addition, PEtOx-based branched MMs bearing a terminal alkyne group were prepared and conjugated to an azide-containing bis-spirocyclohexyl nitroxide via Cu-catalyzed azide-alkyne cycloaddition (CuAAC). ROMP of this branched MM, followed by in situ cross-linking, provided PEtOx-based brush-arm star polymers (BASPs) with nitroxide radicals localized at the core-shell interface. These PEtOx-based nitroxide-containing BASPs displayed relaxivity values on par with state-of-the-art polyethylene glycol (PEG)-based nitroxide materials, making them promising as organic radical contrast agents for metal-free magnetic resonance imaging (MRI)

‘Why haven’t I got one of those?’ A consideration regarding the need to protect non-participant children in early years research

It is widely documented that young children participating in research should be protected from harm and that ethical considerations should be applied throughout a research project. What this paper strives to assert, however, is that protecting these participants is insufficient. A research project into children’s speech and language development, using audio–-visual methods, highlighted that children who are non-participants, those on the periphery of research, can also be affected by the research process. It is acknowledged throughout this paper that although ethical procedures were adhered to whilst undertaking a specific research project, this was insufficient. It is therefore argued that all children within a research environment, whether participatory or not, should be given equal consideration with regards to ethical protection when undertaking research. It is asserted that ‘“why haven’t I got one of those’”, or the equivalent, is a phrase to be avoided at all costs when undertaking research with children

Pro-organic radical contrast agents (“pro-ORCAs”) for real-time MRI of pro-drug activation in biological systems

Nitroxide-based organic-radical contrast agents (ORCAs) are promising as safe next-generation magnetic resonance imaging (MRI) tools. Nevertheless, stimuli-responsive ORCAs that enable MRI monitoring of prodrug activation have not been reported; such systems could open new avenues for prodrug validation and image-guided drug delivery. Here, we introduce a novel “pro-ORCA” concept that addresses this challenge. By covalent conjugation of nitroxides and drug molecules (doxorubicin, DOX) to the same brush-arm star polymer (BASP) through chemically identical cleavable linkers, we demonstrate that pro-ORCA and prodrug activation, i.e., ORCA and DOX release, leads to significant changes in MRI contrast that correlate with cytotoxicity. This approach is shown to be general for a range of commonly used linker cleavage mechanisms (e.g., photolysis and hydrolysis) and release rates. Pro-ORCAs could find applications as research tools or clinically viable “reporter theranostics” for in vitro and in vivo MRI-correlated prodrug activation

Vascular complications associated with intraaortic balloon pump supported percutaneous coronary intervention (PCI) and clinical outcomes from the British Cardiovascular Intervention Society National PCI Database.

INTRODUCTION: The impact of a vascular complication (VC) in the setting of intraaortic balloon pump (IABP) supported PCI on clinical outcomes is unclear. METHODS: Using data from the BCIS National PCI Database, multivariate logistic regression was used to identify independent predictors of a VC. Propensity scoring was used to quantify the association between a VC and outcomes. RESULTS: Between 2007 and 2014, 9,970 PCIs in England and Wales were supported by IABP (1.6% of total PCI), with 224 femoral VCs (2.3%). Annualized rates of a VC reduced as the use of radial access for PCI increased. The independent predictors of a VC included a procedural complication (odds ratio [OR] 2.9, p < .001), female sex (OR 2.3, p < .001), PCI for stable angina (OR 3.47, p = .028), and use of a glycoprotein inhibitor (OR 1.46 [1.1:2.5], p = .04), with a lower likelihood of a VC when radial access was used for PCI (OR 0.48, p = .008). A VC was associated with a higher likelihood of transfusion (OR 5.7 [3.5:9.2], p < .0001), acute kidney injury (OR 2.6 [1.2:6.1], p = .027), and periprocedural MI (OR 3.2 [1.5:6.7], p = .002) but not with adjusted mortality at discharge (OR 1.2 [0.8:1.7], p = .394) or 12-months (OR 1.1 [0.76:1.56], p = .639). In sensitivity analyses, there was a trend towards higher mortality in patients experiencing a VC who underwent PCI for stable angina (OR 4.1 [1.0:16.4], p value for interaction .069). Discussion and Conclusions Although in-hospital morbidity was observed to be adversely affected by occurrence of a VC during IABP-supported PCI, in-hospital and 1-year survival were similar between groups

'To live and die [for] Dixie': Irish civilians and the Confederate States of America

Around 20,000 Irishmen served in the Confederate army in the Civil War. As a result, they left behind, in various Southern towns and cities, large numbers of friends, family, and community leaders. As with native-born Confederates, Irish civilian support was crucial to Irish participation in the Confederate military effort. Also, Irish civilians served in various supporting roles: in factories and hospitals, on railroads and diplomatic missions, and as boosters for the cause. They also, however, suffered in bombardments, sieges, and the blockade. Usually poorer than their native neighbours, they could not afford to become 'refugees' and move away from the centres of conflict. This essay, based on research from manuscript collections, contemporary newspapers, British Consular records, and Federal military records, will examine the role of Irish civilians in the Confederacy, and assess the role this activity had on their integration into Southern communities. It will also look at Irish civilians in the defeat of the Confederacy, particularly when they came under Union occupation. Initial research shows that Irish civilians were not as upset as other whites in the South about Union victory. They welcomed a return to normalcy, and often 'collaborated' with Union authorities. Also, Irish desertion rates in the Confederate army were particularly high, and I will attempt to gauge whether Irish civilians played a role in this. All of the research in this paper will thus be put in the context of the Drew Gilpin Faust/Gary Gallagher debate on the influence of the Confederate homefront on military performance. By studying the Irish civilian experience one can assess how strong the Confederate national experiment was. Was it a nation without a nationalism

What facilitates the delivery of dignified care to older people? A survey of health care professionals Geriatrics

Background: Whilst the past decade has seen a growing emphasis placed upon ensuring dignity in the care of older people this policy objective is not being consistently achieved and there appears a gap between policy and practice. We need to understand how dignified care for older people is understood and delivered by the health and social care workforce and how organisational structures and policies can promote and facilitate, or hinder, the delivery of such care. Methods: To achieve our objective of understanding the facilitators and to the delivery of dignified care we undertook a survey with health and social care professionals across four NHS Trusts in England. Participants were asked provide free text answers identifying any facilitators/barriers to the provision of dignified care. Survey data was entered into SPSSv15 and analysed using descriptive statistics. These data provided the overall context describing staff attitudes and beliefs about dignity and the provision of dignified care. Qualitative data from the survey were transcribed verbatim and categorised into themes using thematic analysis. Results: 192 respondents were included in the analysis. 79 % of respondents identified factors within their working environment that helped them provide dignified care and 68 % identified barriers to achieving this policy objective. Facilitators and barriers to delivering dignified care were categorised into three domains: 'organisational level'; 'ward level' and 'individual level'. Within the these levels, respondents reported factors that both supported and hindered dignity in care including 'time', 'staffing levels', training',' 'ward environment', 'staff attitudes', 'support', 'involving family/carers', and 'reflection'. Conclusion: Facilitators and barriers to the delivery of dignity as perceived by health and social care professionals are multi-faceted and range from practical issues to interpersonal and training needs. Thus interventions to support health and social care professionals in delivering dignified care, need to take a range of issues into account to ensure that older people receive a high standard of care in NHS Trusts.Professor David Oliver, Professor Andree le May, Dr. Sally Richards, Dr Wendy Marti

Theatre and drama education and populism : the ensemble ‘family’ as a space for dialogic empathy and civic care

This article, understanding populism as an essentially undemocratic ideology, argues that the pro‐social theatre education approach of ensemble pedagogy can offer a model of educational practice which counters these anti‐democratic rhetorics by creating a shared space for the enactment of empathetic discourse. Via an ethnography of the UK Shakespeare Schools Foundation festival project, the notion of the theatre education ensemble ‘family’ as a model of civic caring is offered as an alternative, feminist ‘care perspective’ on civic and political rhetorics, in contrast to the patriarchal ‘justice perspectives’ which facilitate the reductive anti‐democratic rhetorics of populism. Thus, this article concludes that ensemble approaches to theatre education, viewed through this feminist pedagogy lens, hold rich potential for developing learners’ capacity to resist populism and act in socially hopeful ways

Observations of Milky Way Dwarf Spheroidal galaxies with the Fermi-LAT detector and constraints on Dark Matter models

We report on the observations of 14 dwarf spheroidal galaxies with the Fermi Gamma-Ray Space Telescope taken during the first 11 months of survey mode operations. The Fermi telescope provides a new opportunity to test particle dark matter models through the expected gamma-ray emission produced by pair annihilation of weakly interacting massive particles (WIMPs). Local Group dwarf spheroidal galaxies, the largest galactic substructures predicted by the cold dark matter scenario, are attractive targets for such indirect searches for dark matter because they are nearby and among the most extreme dark matter dominated environments. No significant gamma-ray emission was detected above 100 MeV from the candidate dwarf galaxies. We determine upper limits to the gamma-ray flux assuming both power-law spectra and representative spectra from WIMP annihilation. The resulting integral flux above 100 MeV is constrained to be at a level below around 10^-9 photons cm^-2 s^-1. Using recent stellar kinematic data, the gamma-ray flux limits are combined with improved determinations of the dark matter density profile in 8 of the 14 candidate dwarfs to place limits on the pair annihilation cross-section of WIMPs in several widely studied extensions of the standard model. With the present data, we are able to rule out large parts of the parameter space where the thermal relic density is below the observed cosmological dark matter density and WIMPs (neutralinos here) are dominantly produced non-thermally, e.g. in models where supersymmetry breaking occurs via anomaly mediation. The gamma-ray limits presented here also constrain some WIMP models proposed to explain the Fermi and PAMELA e^+e^- data, including low-mass wino-like neutralinos and models with TeV masses pair-annihilating into muon-antimuon pairs. (Abridged)Comment: 25 pages, 4 figures, accepted to ApJ, Corresponding authors: J. Cohen-Tanugi, C. Farnier, T.E. Jeltema, E. Nuss, and S. Profum