"Where Everything Goes to Hell": Stephen King as Literary Naturalist

In his bestselling nonfiction book about the horror genre, Danse Macabre, author Stephen King lists among his idols "the great naturalist writer Frank Norris" (336). While King primarily writes horror fiction, he has often noted his indebtedness to early American literary naturalists. As these naturalist writers have been such an influence in King's life and writing, it seems logical to explore whether King himself, in addition to being a horror writer, can also be considered a literary naturalist. By looking at ideas of both early and contemporary American literary naturalism, I explore how a variety of King's works utilize the most central tenets of naturalism, including realism, determinism (biological, environmental, and technological) and the seeming paradox of free will within determined environments. I also look at how King's horror can be compatible with, and even expands on, the definition of traditional literary naturalism

Targeting DNA repair for personalisation of glioblastoma therapy

Background Glioblastomas (GBM) are the most common primary brain tumour in adults in the UK and are associated with a poor prognosis. High expression of MGMT (a direct DNA repair protein) has been shown to decrease response to temozolomide and radiotherapy in GBM. Little, however, is known of the effects of other DNA repair genes on survival and response to treatment in GBM. PTEN is a tumour suppressor gene commonly mutated in high grade glioma. Tumours deficient in PTEN have been shown in some, but not all, studies to have defective DNA double strand break repair. PTEN deficient tumours may therefore be amenable to treatment targeting with a DNA repair inhibitor, exploiting a strategy known as synthetic lethality. In this study the prognostic significance of DNA repair status in high grade glioma will be explored, alongside the effects of ATM inhibitor treatment in PTEN proficient and deficient glioblastoma cell lines. Methods Kaplan Meier survival analysis was performed for the mRNA expression levels of 248 probes (representing 157 DNA repair genes) in two adult glioblastoma datasets (Test dataset [n=191] and TCGA dataset [n=508]). After adjustment for multiple comparisons, multivariate analysis was performed, including genes significantly associated with survival on Kaplan Meier analysis. A DNA repair gene prognostic index was generated incorporating DNA repair genes whose expression was associated with survival on multivariate analysis in both datasets. Artificial neural network analysis (ANN) was conducted in the TCGA dataset to investigate global gene interactions of the five key DNA repair genes included in the prognostic index. The prognostic significance of key genes included in the prognostic index was explored at the protein level in a cohort of 61 adult high grade gliomas (Nottingham cohort) by immunohistochemistry. To explore synthetic lethality in PTEN proficient/deficient glioblastoma, Kaplan Meier survival analysis was performed for both PTEN and ATM mRNA (TCGA cohort) and protein expression (Nottingham cohort). Differences in DNA repair gene expression between PTEN proficient/deficient glioblastoma cell lines was assessed using the RT2 DNA repair PCR array. Sensitivity of these cell lines to the ATM inhibitor KU55933 was assessed using a cell proliferation (MTS) assay. The functional consequences of this treatment were evaluated using the neutral comet assay and flow cytometric analysis of γH2AX accumulation, apoptosis and cell cycle progression. To further validate these findings, doxycycline-inducible PTEN knock-down glioblastoma cell lines were generated using lentiviral delivery of shRNA against PTEN. Results In both the Test and TCGA cohorts, a 14 DNA repair gene expression panel was associated with poor survival. On cox multivariate regression analysis APE1, NBN, PMS2, MGMT and PTEN were found to be independently associated with poor prognosis. A DNA repair prognostic index incorporating APE1, NBN, PMS2, MGMT and PTEN stratified patients into three distinct prognostic sub-groups with worsening survival (p<0.000001). ANN analysis of APE1, NBN, PMS2, MGMT and PTEN revealed interactions with genes involved in the response to hypoxia (HIF1AN), fatty acid metabolism (ACACB, ACSL4), transcriptional response (FOXG1, THRA), and nucleotide metabolism (HPRT). At the protein level, low PTEN (p=0.042) and low APE1 (p=0.031) retained a significant association with poor prognosis. In the subgroup of GBMs with high expression of PTEN, high expression of ATM mRNA (probe 208442_s_at p=0.03, probe 210858_x_at p=0.025) and protein (p=0.022) was associated with worse overall survival than in patients with low ATM expression. In cell lines studies PTEN deficiency was not associated with sensitivity to an ATM inhibitor; however the PTEN proficient LN18 cell line exhibited increased sensitivity to KU55933 treatment. Higher rates of apoptosis and G1 cell cycle arrest were demonstrated in the LN18 cell line in response to 10µM KU55933. KU55933 treatment did not result in an increase in DNA damage (including double strand breaks), as assessed by the neutral comet assay and γH2AX accumulation. Knock-down of PTEN did not significantly influence sensitivity to KU55933. Conclusion DNA repair status clearly has prognostic significance in high grade glioma. There is, however, no evidence to support the use of ATM inhibitors in PTEN deficient GBM. Further work is required to identify why the LN18 PTEN proficient glioblastoma cell line is selectively sensitive to ATM inhibitor treatment

Special Issue on ‘Rethinking Undergraduate Business Education: In the Classroom & Beyond’

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/102659/1/dsji12026.pd

THE POTENTIAL FOR REVENUE INSURANCE POLICIES IN THE SOUTH

The 1996 Farm Act and the 1994 Crop Insurance Reform Act are recent examples of policy changes that have increased risks for U.S. farmers. New products are emerging to help farmers manage risks. This article examines some of the policy changes, farmer responses, and new risk-sharing products. The focus turns to the new revenue insurance products and their potential in the South. While there are reasons to believe revenue insurance should be attractive in the South, any revenue products that use existing crop insurance rates will face difficulties since poor actuarial performance in the South has resulted in relatively high rates.Agricultural policy, Crop insurance, Revenue insurance, Risk, Southern agriculture, Risk and Uncertainty,

Special Issue on ‘Rethinking Undergraduate Business Education: In the Classroom & Beyond’

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/106909/1/dsji12034.pd

Eco-Capabilities: Arts-in-Nature for Supporting Nature Visibilisation and Wellbeing in Children

Estimates of mental health disorders and poor wellbeing among children and young people in England are escalating. While maintaining a positive relationship with nature is thought to promote personal and collective wellbeing, children and young people are spending less time outdoors, exhibiting a lack of appreciation for the environment and degrees of ‘plant blindness’. As such, there is a pressing need on behalf of schools to address these issues, and to adapt to students’ needs for a deeper and more purposeful connection with nature. This study aimed to explore the potential of one avenue to achieving this: arts-in-nature practice. This involved utilising arts-based research methods, through which 97 children aged 7–10 drew their ‘happy place’, alongside participatory observations, and interviews and focus groups with artists and teachers, as part of the wider Eco-Capabilities project. Findings suggest that following the arts-in-nature sessions there was a significant increase in the number of children’s drawings which featured nature as a main focus. This was achieved in three ways: by drawing newfound attention to nature; by attributing increased value to nature; and by explicitly placing nature within the purview of wellbeing. As such, we argue that creative pedagogies outdoors likely enhance what we term ‘nature visibilisation’ in children, an outcome necessary for their personal wellbeing and sustainability of the environment. This has significant implications for school practice in relation to how to support children’s mental health and wellbeing, alongside boosting interest in environmental sustainability and pro-environmental behaviour

Managing Risk in Farming: Concepts, Research, and Analysis

The risks confronted by grain and cotton farmers are of particular interest, given the changing role of the Government after passage of the 1996 Farm Act. With the shift toward less government intervention in the post-1996 Farm Act environment, a more sophisticated understanding of risk and risk management is important to help producers make better decisions in risky situations and to assist policymakers in assessing the effectiveness of different types of risk protection tools. In response, this report provides a rigorous, yet accessible, description of risk and risk management tools and strategies at the farm level. It also provides never-before-published data on farmers' assessments of the risks they face, their use of alternative risk management strategies, and the changes they would make if faced with financial difficulty. It also compares price risk across crops and time periods, and provides detailed information on yield variability.crop insurance, diversification, futures contracts, leasing, leveraging, liquidity, livestock insurance, marketing contracts, options contracts, production contracts, revenue insurance, risk, vertical integration, Farm Management, Risk and Uncertainty,

Practice Report: Student Health Ambassadors at Residential Campuses Contribute to Safer Campus Living and Learning During the COVID-19 Pandemic

In summer 2020 six residential institutions of higher education (IHE) and the Mountain Area Health Education Center (MAHEC) in Western North Carolina chose a collaborative approach to mitigating COVID-19 infection rates on campus. This approach shares the practices and successes of this concerted effort with a focus on a large public, medium public, and small private IHE. The campuses promoted a healthy and safe culture through a rigorous and transformational learning experience and focused on engaging Student Health Ambassadors (SHAs) in applying the Diffusion of Innovations model to peer-topeer gain-framed messaging for health. Three institutions’ programs are presented and cross-case analysis is used to illuminate transferable promising practices. Promising transferable practices across the schools include: selecting the right students, strong institutional support, the three Ps (positive, proactive and prevention-focused), building leadership skills, and peer-led campus culture change. Transferable insights from the practices at three campuses focused on the role and impact of peer-to-peer student health ambassadors on campus to mitigate the spread of COVID-19

Expression and Role of PIWI Proteins and piRNAs in Reproduction of Water Buffalo (Bubalus bubalis, Linn.)

High-fertile and productive dairy animals are important to satisfy the growing population's demand. Sire fertility is one of the essential factors that regulate the overall pregnancy rate of dairy herds. However, sire fertility varies from 10 to 90%, suggesting that male fertility largely accounts for varying fertility levels across the herd. Sub-fertile bulls and females should be identified and discarded promptly to improve the dairy herd's productivity. The most dominant factors implicated in culling are poor semen quality, poor semen freezability (&lt;35% post-thaw motility), and poor libido for the bulls and hard breeders for females that cause huge economic loss to the raisers. Understanding the basic mechanism of male and female fertility has undergone tremendous change in recent times owing to the advancement of molecular tools judging the essential molecules responsible for fertility. Presently, a new molecular niche has surfaced in testes, strongly influencing the fertilization potential of spermatozoa. Over the last decade, there has arrived a conclusion that out of several factors, piRNA and PIWI proteins are largely implicated in regulating the vital aspects of fertility and embryogenesis. While this development is advancing in other animals, very limited information is available on PIWI protein and piRNAs in large animals. Except for a few sporadic information on PIWI protein in cattle, very limited information is available on piRNAs and PIWI protein in regulation with buffalo bull fertility and growth of embryos of buffaloes, posting a huge demand for research

Promoting medical students’ reflection on competencies to advance a global health equities curriculum

Abstract Background The move to frame medical education in terms of competencies – the extent to which trainees “can do” a professional responsibility - is congruent with calls for accountability in medical education. However, the focus on competencies might be a poor fit with curricula intended to prepare students for responsibilities not emphasized in traditional medical education. This study examines an innovative approach to the use of potential competency expectations related to advancing global health equity to promote students’ reflections and to inform curriculum development. Methods In 2012, 32 medical students were admitted into a newly developed Global Health and Disparities (GHD) Path of Excellence. The GHD program takes the form of mentored co-curricular activities built around defined competencies related to professional development and leadership skills intended to ameliorate health disparities in medically underserved settings, both domestically and globally. Students reviewed the GHD competencies from two perspectives: a) their ability to perform the identified competencies that they perceived themselves as holding as they began the GHD program and b) the extent to which they perceived that their future career would require these responsibilities. For both sets of assessments the response scale ranged from “Strongly Disagree” to “Strongly Agree.” Wilcoxon’s paired T-tests compared individual students’ ordinal rating of their current level of ability to their perceived need for competence that they anticipated their careers would require. Statistical significance was set at p < .01. Results Students’ ratings ranged from “strongly disagree” to “strongly agree” that they could perform the defined GHD-related competencies. However, on most competencies, at least 50 % of students indicated that the stated competencies were beyond their present ability level. For each competency, the results of Wilcoxon paired T-tests indicate – at statistically significant levels - that students perceive more need in their careers for GHD-program defined competencies than they currently possess. Conclusion This study suggests congruence between student and program perceptions of the scope of practice required for GHD. Students report the need for enhanced skill levels in the careers they anticipate. This approach to formulating and reflecting on competencies will guide the program’s design of learning experiences aligned with students’ career goals.http://deepblue.lib.umich.edu/bitstream/2027.42/109541/1/12909_2013_Article_919.pd