Coronal Plane: Cristin Millett

Coronal Plane is the culmination of Millett’s research on the anatomical theater at the University of Padua built in 1594, the oldest surviving anatomy theater in the world. The installation allows viewers to walk into and through a space that evokes physical, emotional, and psychological reactions similar to those experienced in the historic anatomy theater in Padua by audiences of the past. Illustrations depicted on red “windows” in Millett’s work are appropriated from De Formato Foetu, a text written by Girolamo Fabrizi d’Acquapendente (Hieronymus Fabricius), the Chair of Anatomy at the University of Padua. It was under his leadership that the anatomy theater of 1594 was built. Millett’s allusions to Catholic confessionals and kneeling benches in the installation invite the viewer to question the contradictory stance between surgeries performed for medical education and dissections completed in order to disperse sacred remains for widespread worship. Particular references to sexuality and sexual differences are also central to Millett’s investigation of historical medical practices and philosophies. The University of Padua was one of the first institutions that dissected both male and female cadavers.https://cupola.gettysburg.edu/artcatalogs/1026/thumbnail.jp

Examining local processes when applying a cumulative impact policy to address harms of alcohol outlet density.

One approach to addressing the negative health and social harms of excessive drinking has been to attempt to limit alcohol availability in areas of high outlet density. The Licensing Act (2003) enables English local authorities the power to implement a Cumulative Impact Policy (CIP) in order to tackle alcohol challenges. More than 100 English local authorities have implemented a CIP in one or more designated areas. We examined local licence decision-making in the context of implementing CIPs. Specifically, we explored the activities involved in alcohol licensing in one London local authority in order to explicate how local decision-making processes regarding alcohol outlet density occur. Institutional ethnographic research revealed that CIPs were contested on multiple grounds within the statutory licensing process of a local authority with this policy in place. CIPs are an example of multi-level governance in which national and local interests, legal powers and alcohol licensing priorities interface. Public health priorities can be advanced in the delivery of CIPs, but those priorities can at times be diluted by those of other stakeholders, both public sector and commercial

Modifying the self-assembled nanostructures of perylene bisimides in water and their applications

Perylene bisimide (PBI) performance in photovoltaic applications is highly dependent on their ability to form photogenerated radicals. Their aggregation and self-assembled nanostructures can have a large impact on their ability to form the photoconductive radical. Currently, the literature has been primarily focused on changing their aggregation and self-assembled nanostructures in organic solvents. However, there is a desire to move away from organic solvents and towards water as it is more environmentally friendly. The addition of pH sensitive groups onto the PBI chemical structure allows for them to be solubilised in water. This also allows for their aggregation and self-assembled nanostructures to be tailored through pH change. First, this work looked at how the counterion used to make the basic solution which solubilises the PBI could be used to change the aggregates and molecular packing in solution. This is a simple method and less time consuming compared to changing the PBI chemical structure to form new structures. The different metal ions used to form the PBI aggregates had different pH sensitivities and showed different nanostructures forming over a range of pHs. This also led to a change in the gelation kinetics for pH-triggered hydrogels and a difference in the bulk rheological properties. The solutions of PBI solubilised with different counterions at pH 6 were used to fabricate multilayer photovoltaic devices which showed varying degrees of power conversion efficiency depending on counterion choice. Next, the chemical structure was changed in the imide position with three similar amino acids. These PBIs were then characterised across various length scales to see how their self-assembled structures influenced their ability to form photoconductive radical at different pHs. This difference in molecular packing led to a difference in radical anion formation over a range of pHs. The difference in pH sensitivity led to a difference in the gelation kinetics when a pH trigger was used. It was also observed that the different pH sensitivities led to an increase in gel stiffness for one of the PBIs. Lastly the synthesis of three PBIs with different amino acid side chains that have been core-substituted with pyrrolidine groups were examined. The change in the functional group on the core is expected to change the π-π stacking. The addition of the electron density to the core leads to a dramatic change in the optical and redox properties. The PBIs were able to form radical cation instead of radical anion when irradiated. Their ability to self-assemble as pH was lowered showed that amino acid choice has a major impact on the nanostructures formed. They could be used to make pH-triggered hydrogels when the initial solution concentration was increased, however, these hydrogels could no longer form radical cation

Challenging, co-operating and splitting: a qualitative analysis of how the trade press responded to cumulative impact policies in England and Wales

Introduction: Cumulative impact policies (CIPs) increase English and Welsh local authority powers to regulate licences to sell alcohol. Commercial actors’ responses to CIPs potentially affect implementation and impacts. An analysis of the trade press provides perspectives on how commercial actors respond to this intervention. Methods: Qualitative, thematic analysis of trade press articles (published 2003–2016, n = 6 trade journals) focusing on depictions and responses to CIPs, including strategies for commercial actors engaging with the intervention. Results: Included articles (n = 257) provided both positive, but more typically, negative depictions of CIPs. CIPs were criticised for being unfair and an economic threat. Legal challenges to CIPs were at times advocated. Partnership and dialogue with local authority stakeholders were presented as a means by which licence applicants could promote their commercial interests in areas where CIPs were implemented, or as an alternative to regulatory interventions such as CIPs. Some alcohol retailers hoped CIPs could protect their businesses from market competition. Conclusions: Commercial actors do not respond uniformly to alcohol regulation. This study of CIPs found that at times different commercial interests could be served by directly challenging the intervention or strategically co-operating with implementers. Implementation and evaluation of such interventions should consider commercial actors’ responses

Mesenchymal stromal cells (MSCs) and colorectal cancer - a troublesome twosome for the anti-tumour immune response?

The tumour microenvironment (TME) is an important factor in determining the growth and metastasis of colorectal cancer, and can aid tumours by both establishing an immunosuppressive milieu, allowing the tumour avoid immune clearance, and by hampering the efficacy of various therapeutic regimens. The tumour microenvironment is composed of many cell types including tumour, stromal, endothelial and immune cell populations. It is widely accepted that cells present in the TME acquire distinct functional phenotypes that promote tumorigenesis. One such cell type is the mesenchymal stromal cell (MSC). Evidence suggests that MSCs exert effects in the colorectal tumour microenvironment including the promotion of angiogenesis, invasion and metastasis. MSCs immunomodulatory capacity may represent another largely unexplored central feature of MSCs tumour promoting capacity. There is considerable evidence to suggest that MSCs and their secreted factors can influence the innate and adaptive immune responses. MSC-immune cell interactions can skew the proliferation and functional activity of T-cells, dendritic cells, natural killer cells and macrophages, which could favour tumour growth and enable tumours to evade immune cell clearance. A better understanding of the interactions between the malignant cancer cell and stromal components of the TME is key to the development of more specific and efficacious therapies for colorectal cancer. Here, we review and explore MSC- mediated mechanisms of suppressing anti-tumour immune responses in the colon tumour microenvironment. Elucidation of the precise mechanism of immunomodulation exerted by tumour-educated MSCs is critical to inhibiting immunosuppression and immune evasion established by the TME, thus providing an opportunity for targeted and efficacious immunotherapy for colorectal cancer growth and metastasis

Prevalence of Victimisation in Autistic Individuals: A Systematic Review and Meta-Analysis

Autistic individuals are at an increased risk of experiencing victimisation. Previous reviews have focussed specific types of victimisation. Thus, a clearer picture considering the range of victimisation experiences autistic people face is required. This systematic review aims to identify the prevalence of victimisation in autistic individuals considering a variety of victimisation types (e.g., bulling, sexual victimisation, and crime) in both adults and children from clinical and community settings. Through systematic searches of relevant databases, 291 studies met the criteria for review. Of those, 34 studies met the inclusion criteria: a) quantitative studies, b) involving autistic individuals, c) reporting prevalence rates of victimisation. Meta-analysis found a pooled prevalence rate of victimisation of 44% in autistic individuals. Subgroup analysis examined moderating factors as high heterogeneity was present. This found the pooled prevalence rates for bullying to be 47%, 16% for child abuse, 40% for sexual victimisation, 13% for cyberbullying, and 84% for multiple forms of victimisation in autistic individuals, though heterogeneity remained. Correction for participants’ age, reporter used, and the population which the sample was recruited from did not reduce heterogeneity. Although heterogeneity impedes the definitive interpretation of the findings, this review illustrates the need for strategies and interventions to reduce the incidence of victimisation

Divergent amino acid and sphingolipid metabolism in patients with inherited neuro-retinal disease

OBJECTIVES: The non-essential amino acids serine, glycine, and alanine, as well as diverse sphingolipid species, are implicated in inherited neuro-retinal disorders and are metabolically linked by serine palmitoyltransferase (SPT), a key enzyme in membrane lipid biogenesis. To gain insight into the pathophysiological mechanisms linking these pathways to neuro-retinal diseases we compared patients diagnosed with two metabolically intertwined diseases: macular telangiectasia type II (MacTel), hereditary sensory autonomic neuropathy type 1 (HSAN1), or both. METHODS: We performed targeted metabolomic analyses of amino acids and broad sphingolipids in sera from a cohort of MacTel (205), HSAN1 (25) and Control (151) participants. RESULTS: MacTel patients exhibited broad alterations of amino acids, including changes in serine, glycine, alanine, glutamate, and branched-chain amino acids reminiscent of diabetes. MacTel patients had elevated 1-deoxysphingolipids but reduced levels of complex sphingolipids in circulation. A mouse model of retinopathy indicates dietary serine and glycine restriction can drive this depletion in complex sphingolipids. HSAN1 patients exhibited elevated serine, lower alanine, and a reduction in canonical ceramides and sphingomyelins compared to controls. Those patients diagnosed with both HSAN1 and MacTel showed the most significant decrease in circulating sphingomyelins. CONCLUSIONS: These results highlight metabolic distinctions between MacTel and HSAN1, emphasize the importance of membrane lipids in the progression of MacTel, and suggest distinct therapeutic approaches for these two neurodegenerative diseases

Sustainability as corporate culture of a brand for superior performance

This is the post-print version of the final paper published in the Journal of World Business. The published article is available from the link below. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. Copyright @ 2012 Elsevier B.V.Sustainability research highlights new challenges and opportunities for businesses. This paper reviews the literature to understand the ability of sustainable green initiatives when practiced as a corporate culture to individually create new opportunities for operations, management and marketing. According to current research, business opportunities exclusively available to different functions of a firm can drive its performance. The role of marketing in the achievement of superior performance by virtue of sustainability practices is also explained by the existing literature. Branding literature, however, fails to explain the influence of a brand on sustainability-driven opportunities available to a firm for superior performance. The objective of this study is to explore if a brand can strengthen the ability of sustainability-based green initiatives of managers to drive opportunities available to a firm for superior performance. A conceptual framework grounded in the triple bottom line theory is presented based on the assumption that brand as a stimulating factor can accelerate the conversion of opportunities available to a business into superior performance. Academic and managerial perspectives have been used to draw upon the implications of the model. Both practitioners and academic researchers will benefit from future research on this topic

Quantitative cross-species extrapolation between humans and fish: The case of the anti-depressant fluoxetine

This article has been made available through the Brunel Open Access Publishing Fund.Fish are an important model for the pharmacological and toxicological characterization of human pharmaceuticals in drug discovery, drug safety assessment and environmental toxicology. However, do fish respond to pharmaceuticals as humans do? To address this question, we provide a novel quantitative cross-species extrapolation approach (qCSE) based on the hypothesis that similar plasma concentrations of pharmaceuticals cause comparable target-mediated effects in both humans and fish at similar level of biological organization (Read-Across Hypothesis). To validate this hypothesis, the behavioural effects of the anti-depressant drug fluoxetine on the fish model fathead minnow (Pimephales promelas) were used as test case. Fish were exposed for 28 days to a range of measured water concentrations of fluoxetine (0.1, 1.0, 8.0, 16, 32, 64 μg/L) to produce plasma concentrations below, equal and above the range of Human Therapeutic Plasma Concentrations (HTPCs). Fluoxetine and its metabolite, norfluoxetine, were quantified in the plasma of individual fish and linked to behavioural anxiety-related endpoints. The minimum drug plasma concentrations that elicited anxiolytic responses in fish were above the upper value of the HTPC range, whereas no effects were observed at plasma concentrations below the HTPCs. In vivo metabolism of fluoxetine in humans and fish was similar, and displayed bi-phasic concentration-dependent kinetics driven by the auto-inhibitory dynamics and saturation of the enzymes that convert fluoxetine into norfluoxetine. The sensitivity of fish to fluoxetine was not so dissimilar from that of patients affected by general anxiety disorders. These results represent the first direct evidence of measured internal dose response effect of a pharmaceutical in fish, hence validating the Read-Across hypothesis applied to fluoxetine. Overall, this study demonstrates that the qCSE approach, anchored to internal drug concentrations, is a powerful tool to guide the assessment of the sensitivity of fish to pharmaceuticals, and strengthens the translational power of the cross-species extrapolation