Obesity and postmenopausal breast cancer : determining the role of local aromatase expression

textObesity is associated with a worse breast cancer prognosis, particularly in estrogen receptor alpha (ER alpha) positive, postmenopausal patients. It has also been correlated with elevated levels of inflammation, which can stimulate adipose tissue aromatase expression and subsequent estrogen production. Given that obese patients have a lower response rate to aromatase inhibitor treatment and greater mammary tissue aromatase levels, it was hypothesized that obesity promotes ER alpha positive postmenopausal breast cancer progression in part via an inflammation-induced increase in mammary tissue aromatase expression and ER alpha activity. These studies utilized an in vitro model of obesity in which cultured cells were exposed to postmenopausal breast cancer patients’ serum samples, pooled by body mass index category (Obese (OB): ≥30.0 kg/m2; Normal weight (N): 18.5-24.9 kg/m2). OB versus N patient sera induced greater breast cancer cell (BCC) aromatase expression, as well as higher ER alpha activity and cell viability in the presence of testosterone, the substrate for aromatase. Pre-adipocytes exposed to OB versus N patient sera also indirectly stimulated greater BCC aromatase expression, ER alpha activity, and viability. A retrospective review of breast cancer patient data demonstrated that daily use of non-steroidal anti-inflammatory drugs, which inhibit cyclooxygenase-2 (COX-2) activity, is associated with reduced ER alpha positive breast cancer recurrence in obese and overweight women. The mechanisms mediating this effect were examined using the same in vitro model. Exposure to OB versus N patient sera stimulated greater macrophage and BCC COX-2 expression and prostaglandin E2 production, leading to enhanced pre-adipocyte aromatase expression. These OB patient sera-induced effects were further linked with greater BCC ER alpha activity, proliferation, and migration in the presence of testosterone, and these differences were eliminated or reduced with aromatase inhibition. Based on these findings, prospective studies designed to examine the clinical benefit of NSAID use in obese ER alpha positive postmenopausal breast cancer patients are warranted. Additional obesity-associated mechanisms that may also promote breast cancer progression were also explored, including enhanced cross-talk between non-genomic ER alpha and growth factor signaling pathways, reduced estrogen receptor beta expression, and resistance to chemotherapy. Finally, the impact of obesity on tumor incidence and characteristics in the MMTV-Wnt1 mouse model of mammary carcinogenesis was explored.Nutritional Science

Why surplus structure is not superfluous

The idea that gauge theory has `surplus' structure poses a puzzle: in one much discussed sense, this structure is redundant; but on the other hand, it is also widely held to play an essential role in the theory. In this paper, we employ category-theoretic tools to illuminate an aspect of this puzzle. We precisify what is meant by `surplus' structure by means of functorial comparisons with equivalence classes of gauge fields, and then show that such structure is essential for any theory that represents a rich collection of physically relevant fields which are `local' in nature

The Impact of Trauma on Graduate Occupational Therapy Students: Trauma-Informed Implications for Educators

Recent worldwide events have led to a dramatic increase in reported levels of anxiety in college students and individuals aged 18-29. If there is currently a marked increase in anxiety and stress responses in college age students and traumatic events negatively impact an individual’s ability to participate in their education, it is reasonable to assume that the occupational disruption that students are currently experiencing negatively impacts their ability to participate adequately in their education. This study explored the impact of trauma on graduate occupational therapy students (OTS) from entry-level programs. A mixed-methods survey was utilized to gain the perspectives of graduate OTS (n=74) currently attending programs in the Northeastern portion of the United States who have experienced acute, chronic, and/or complex trauma. Participants completed an online survey consisting of 26 Likert-style, true/false, and open-ended short answer questions. Results indicate that trauma is highly impactful on all areas of occupation, including education. Additionally, students indicated that they are fearful of stigma when discussing trauma and informing educators of its impacts on education, therefore benefiting from open and communicative educators. Further, results support previous research that trauma influences many aspects of academic performance, such as attention, memory, and volition. The information gathered indicates that educators should be aware of the likelihood of students being impacted by trauma and understand how to successfully support students universally through trauma-informed strategies

Homological perspective on edge modes in linear Yang-Mills theory

We provide an elegant homological construction of the extended phase space for linear Yang-Mills theory on an oriented and time-oriented Lorentzian manifold M with a time-like boundary ∂M that was proposed by Donnelly and Freidel [JHEP 1609, 102 (2016)]. This explains and formalizes many of the rather ad hoc constructions for edge modes appearing in the theoretical physics literature

Identification of Emotional Facial Expressions: Effects of Expression, Intensity, and Sex on Eye Gaze

<p>Accuracy of emotion recognition for female (A) and male (B) faces, and response times for classifying female (C) and male (D) faces, by expression, and intensity.</p

Textual Sensibilities: The Physicality of British Poetry, 1750-1850

My dissertation argues that key eighteenth and early nineteenth-century poets - including James Thomson and James Macpherson, Thomas Chatterton, Charlotte Smith, and Erasmus Darwin, and William Blake, John Keats, and Percy Shelley - are united by a preoccupation with the physical properties of the text, language, or both. I argue that these writers take the central period concept of sensibility, or the human capacity for sensory perception and emotion, and reconceive it as a textual category, exploring what I call textual sensibility, or the text's capacity to stimulate the senses relative to its intellectual comprehensibility. In major poems these writers foreground the visual and sonic characteristics of words, punctuation, and space, and use various poetic "units"- from one letter to the entire poem - as physical things or effects that frustrate informational reading and force a more experiential approach to the text. I argue that these techniques arise from the widespread focus on the senses in eighteenth and early nineteenth-century British culture. The dissertation's first chapter defines the salient techniques of physical poetic practice in a range of eighteenth and early nineteenth-century texts; the other chapters concentrate specifically on Blake, Keats, and Shelley as poets who pursue particularly rich, complex, and self-reflexive forms of physical poetic style. My study fills a gap in coverage in the larger field of interest in material affect, which has tended to focus on virtually every other literary period at the expense of the eighteenth and early nineteenth centuries. Jerome McGann's The Poetics of Sensibility touches upon "affective" versus "referential" language in certain late eighteenth-century poets, and scholars have addressed Blake's material uses of word and image and some aspects of Keats's sensory style. But my study supplies an in-depth account of the diverse techniques of physical poetic practice in the eighteenth and early nineteenth-century period, and of the important epistemological inquiry that underlies them: is reading, and particularly reading poetry, about gaining "information" from the text or "experiencing" it, and can these two effects be combined

Secondary survivors of trauma: a research portfolio on the experiences of non-offending caregivers whose children have disclosed sexual abuse

Background: Non-offending caregivers (NOCs) of children who have disclosed sexual abuse have a vital role in supporting their child post-disclosure. Nevertheless, research indicates that NOCs experience clinically elevated levels of distress, which may impact their ability to support their child. Despite this, services have been found to often overlook the support needs of NOCs and there are gaps in the literature around NOCs’ own experiences and distress post-disclosure. This research portfolio aimed to address these research gaps in two parts: 1) a systematic review investigating what key factors have been found to be associated with NOCs’ psychological distress; and 2) a mixed-methods empirical paper exploring NOCs’ post-disclosure experiences, with secondary aims to investigate their help-seeking experiences and the psychological construct ‘mentalization’ in this population. Method: A systematic search of quantitative literature was conducted to identify papers exploring the association of key factors, such as psychosocial, environmental, personal, familial and abuse-related characteristics, with NOCs’ psychological distress. An appraisal tool was used to assess the quality of the studies. The empirical paper adopted a predominantly qualitative mixed-methods design which primarily involved an in-depth exploration of the post-disclosure and help-seeking experiences of NOCs via interviews, with mentalization being measured via a questionnaire. Grounded theory was used to integrate these findings into a model illustrating the themes derived from the data. Results: The systematic review indicated that psychological factors, such as cognitive processes, as well as social and environmental factors, such as social support, had the most evidence for being associated with distress. The evidence was weaker and the findings were more contradictory for the associations between other factors and psychological distress, including NOCs’ abuse history, abuse-related factors, and child and parent characteristics. The empirical study’s grounded theory model centred around core categories of NOCs’ perceptions of feeling out of control and isolated. These linked to other themes around the parental role, including parental self-efficacy, as well as the importance of feeling listened to and supported by the wider system, including services. Quantitative mentalization scores were linked with emotional expressiveness in interviews. Qualitative themes related to mentalization were indicated to be linked to NOCs’ distress in the more immediate disclosure aftermath. Conclusions: While tentative inferences can be made from the systematic review about the most important factors associated with NOCs’ distress, methodological issues in the studies made it difficult to draw firm conclusions. For example, the predominantly cross-sectional nature of studies and their exploration of factors in isolation meant that a more in-depth understanding of interactional processes over time was not possible. The grounded theory model suggests that NOCs have complex multifaceted experiences post-disclosure, characterised by interacting processes linking to their distress. These are not fully accounted for in existing theories of secondary traumatization. Clinical and future research implications are discussed