148 research outputs found

    The Psychological Lives of the Poor

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    All individuals rely on a fundamental set of mental capacities and functions, or bandwidth, in their economic and non-economic lives. Yet, many factors associated with poverty, such as malnutrition, alcohol consumption, or sleep deprivation, may tax this capacity. Previous research has demonstrated that such taxes often significantly alter judgments, preferences, and decision-making. A more suggestive but growing body of evidence points toward potential effects on productivity and utility. Considering the lives of the poor through the lens of bandwidth may improve our understanding of potential causes and consequences of poverty

    Using Mouse Models to Investigate the Initiation and Progression of Pancreatic Cancer

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    Pancreatic cancer is one of the deadliest human malignancies. Standard chemotherapy approaches have proven ineffective , highlighting the need to understand the basic biology of the disease in order to identify future therapeutic targets. In humans, pancreatic tumors almost universally display activating mutations in the oncogene Kras, which are considered to be the initiating factor in carcinogenesis. Pancreatic cancer is also associated with later mutations in tumor suppressors, commonly point mutations in the gene p53. This information from human tumors is used to model pancreatic cancer in mice, where expression of oncogenic Kras recapitulates the precursor lesions seen in humans. Addition of tumor suppressor mutations leads to mice that reliably mimic all the stages of human disease. The overarching goal of this work is to use existing mouse models, as well as develop new ones, in order to further our understanding of the initiation and progression of pancreatic cancer. In the first part of this dissertation, I focus on the initiation of pancreatic cancer and the role of the epigenetic regulator Bmi1. Using a mouse model of early pancreatic carcinogenesis, I show that pancreatic expression of Bmi1 is required for the development of precancerous lesions, and therefore the initiation of pancreatic cancer. I showed that Bmi1 knockdown in pancreatic cancer cell lines increased levels of reactive oxygen species (ROS), indicating that the requirement of Bmi1 expression during pancreatic cancer initiation may be due to its control of cellular ROS levels. Next, I explore the mechanism for Bmi1 requirement in pancreatic cancer initiation. I find that when Bmi1 is knocked down in pancreatic cancer cells, HIF1a is also down, suggesting that Bmi1 is regulating HIF1a. In vivo, pancreatic HIF1a stabilization recovers the lack of precancerous lesion phenotype seen in animals lacking Bmi1 expression, indicating that the reason for Bmi1 requirement in pancreatic cancer initiation is through regulation of HIF1a levels. In the next sections of this dissertation work, I develop new mouse models that will help in the understanding of the basic biology of pancreatic cancer. First, I analyze HIF2a stabilization in the murine pancreas. Pancreatic HIF2a stabilization results in a phenotype that resembles human chronic pancreatitis, including inflammatory infiltrates and extensive fibrosis. In the context of oncogenic Kras expression, HIF2a stabilization leads to the development of large cystic lesions that resemble human mucinous cystic neoplasm (MCN), a less common precancerous lesion of pancreatic cancer. This work provides new mouse models of chronic pancreatitis and MCN, which can be of use in the future to study these conditions. Next, I create a new mouse model to study the role of tumor suppressor mutations in pancreatic cancer. In this work I create a new model that uses the second most common point mutation in p53, as well as models the sequence of events that occur in human tumors. I use these mice to determine that mutant p53 expression promotes formation of precancerous lesions, but it is not necessary for the growth of established tumors. Taken together, this dissertation work utilizes both existing and newly developed mouse models in order to provide new insights into the initiation and progression of pancreatic cancer. Overall, the use of mouse models provides an important scientific basis for experimentation that will eventually lead to new therapeutic options for pancreatic cancer, a truly devastating disease.PHDCellular & Molec Biology PhDUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttps://deepblue.lib.umich.edu/bitstream/2027.42/155270/1/schofihe_1.pd

    The Psychological Lives of the Poor

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    Plant Collecting for the Ecological Garden and the Scottish Heath Garden at the Royal Botanic Garden Edinburgh

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    The Ecological and Heath Gardens at the Royal Botanic Garden Edinburgh were created in 1991 and 1997 respectively. The Ecological Garden started as a naturalistic area of native woodland plants where cryptogams were encouraged to grow. Building on its success other habitat types were created nearby. The Heath Garden replaced an older heather garden and sought to recreate the ‘feel’ of a Scottish upland heathland. In recent years additional wild origin material of conservation concern has been added to each Garden and this paper describes the process along with some of the plants selected

    The Benefits of Interdisciplinary Collaboration in Community-Engaged Research: Insights From a Study of Digital Storytelling With Marginalized Youth

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    This article draws on qualitative data from a long-term partnership to exemplify the unique advantages of interdisciplinary and collaborative approaches in community-engaged research. We demonstrate how the differing foci and intersecting concerns of our scholarly fields, social work and media studies, benefited our work with marginalized communities to promote youth voice through digital storytelling. This effort was grounded in the shared view that digital storytelling offers an excellent opportunity to engage creatively with young people’s memories and experiences and that such storytelling can support young people in their healing, identity formation, agency development, and engagement with the public. By working together across disciplines, we were able to surface and address concerns related to vulnerability, privacy, and advocacy among young people experiencing marginalization in ways that would not have been possible in a project involving only social work or media studies. We illustrate this process by describing three critical incidents that exposed our disciplinary overlaps and differences in ways that helped us navigate complex issues related to young people shared their stories with the public. Our findings therefore have implications for others working with vulnerable communities to amplify counternarratives with the goal of bringing about positive systemic change

    Facial expression modifies female body perception

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    The judgment of female body appearance has been reported to be affected by a range of internal (e.g., viewers’ sexual cognition) and external factors (e.g., viewed clothing type and colour). This eye-tracking study aimed to complement previous research by examining the effect of facial expression on female body perception and associated body-viewing gaze behaviour. We presented female body images of Caucasian avatars in a continuum of common dress sizes posing seven basic facial expressions (neutral, happiness, sadness, anger, fear, surprise, and disgust), and asked both male and female participants to rate the perceived body attractiveness and body size. The analysis revealed an evident modulatory role of avatar facial expressions on body attractiveness and body size ratings, but not on the amount of viewing time directed at individual body features. Specifically, happy and angry avatars attracted the highest and lowest body attractiveness ratings, respectively, and fearful and surprised avatars tended to be rated slimmer. Interestingly, the impact of facial expression on female body assessment was not further influenced by viewers’ gender, suggesting a ‘universal’ role of common facial expressions in modifying the perception of female body appearance

    Overthickening of sedimentary sequences by igneous intrusions

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    This study was part of a collaboration between the University of Aberdeen, Siccar Point Energy Ltd and Integrated Geochemical Interpretation (IGI). Siccar Point Energy Ltd are thanked for giving the author permission to publish. Karolina Harvie and Kevin Ward from Petrosys are thanks for their support during the mapping process of the project. The lead author’s PhD is funded by JX Nippon Exploration and Production (U.K.) Limited as part of the Volcanic Margin Research Consortium Phase 2. PGS are thanked for allowing the author access to the MegaSurveyPlus and PGS/TGS FSB 2011-12 MultiClient GeoStreamer data and for granting permission to publish this work. Seismic interpretation was carried out using Schlumberger Petrel software. Well log analysis was carried out using Schlumberger Techlog software. Dave Ellis and Victoria Pease are thanked for the comments which greatly improved the revisions of this paper. Well data was obtained from the UK Oil and Gas Authority (OGA) Common Data Access (CDA).Peer reviewedPostprin

    Health literacy and use and trust in health information

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    This is a post-print of an article whose final version has been published in Journal of Health Communication, Taylor and Francis, 2018.There is a need to investigate which health information sources are used and trusted by people with limited health literacy to help identify strategies for addressing knowledge gaps that can contribute to preventable illness. We examined whether health literacy was associated with people?s use of and trust in a range of potential health information sources. Six hundred participants from a GfK Internet survey panel completed an online survey. We assessed health literacy using the Newest Vital Sign, the sources participants used to get health information, and the extent to which participants trusted health information from these sources. We performed multivariable regressions, controlling for demographic characteristics. Lower health literacy was associated with lower odds of using medical websites for health information and with higher odds of using television, social media, and blogs or celebrity webpages. People with lower health literacy were less likely to trust health information from specialist doctors and dentists, but more likely to trust television, social media, blogs/celebrity webpages, friends, and pharmaceutical companies. People with limited health literacy had higher rates of using and trusting sources such as social media and blogs, which might contain lower quality health information compared to information from healthcare professionals. Thus, it might be necessary to enhance the public's ability to evaluate the quality of health information sources. The results of this study could be used to improve the reach of high quality health information among people with limited health literacy and thereby increase the effectiveness of health communication programs and campaigns.Peer reviewedCommunity Health Sciences, Counseling and Counseling Psycholog

    Mutant p53R270H drives altered metabolism and increased invasion in pancreatic ductal adenocarcinoma

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    Pancreatic cancer is characterized by nearly universal activating mutations in KRAS. Among other somatic mutations, TP53 is mutated in more than 75% of human pancreatic tumors. Genetically engineered mice have proven instrumental in studies of the contribution of individual genes to carcinogenesis. Oncogenic Kras mutations occur early during pancreatic carcinogenesis and are considered an initiating event. In contrast, mutations in p53 occur later during tumor progression. In our model, we recapitulated the order of mutations of the human disease, with p53 mutation following expression of oncogenic Kras. Further, using an inducible and reversible expression allele for mutant p53, we inactivated its expression at different stages of carcinogenesis. Notably, the function of mutant p53 changes at different stages of carcinogenesis. Our work establishes a requirement for mutant p53 for the formation and maintenance of pancreatic cancer precursor lesions. In tumors, mutant p53 becomes dispensable for growth. However, it maintains the altered metabolism that characterizes pancreatic cancer and mediates its malignant potential. Further, mutant p53 promotes epithelial-mesenchymal transition (EMT) and cancer cell invasion. This work generates new mouse models that mimic human pancreatic cancer and expands our understanding of the role of p53 mutation, common in the majority of human malignancies
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