The Grove: Stories of Cultivating Connections

This thesis studies the University of Mississippi’s tailgating area known as the Grove. While it explores the logistics and preparation for home game activities, this thesis looks beyond the image and into aspects not so obvious to the weekend visitor: its history, its environmental impact, the economics, and even its reflection of the progress and challenges surrounding race. This is not intended to be a supreme authority or academic analysis of the Grove, but instead a journalistic piece reflecting the stories and personal anecdotes I encountered. To gather information, I conducted live interviews with people familiar to the Grove in unique ways and supplemented their stories with information from websites, magazines and newspapers. This project uncovers how the Grove became vital to campus life, why it is still important and how it’s influential as a socializer at the university

The Acute Effect of Exposure to Barefoot Running on VO2 Peak, Fatigue, and Time to Exhaustion in Recreational Runners

Please refer to the pdf version of the abstract located adjacent to the title

Alkaloid inspired spirocyclic oxindoles from 1,3-dipolar cycloaddition of pyridinium ylides

Cycloaddition reactions between pyridinium ylides and 3-alkenyl oxindoles that proceed in high yield and with very good regio- and diastereoselectivity are reported. The resulting cycloadducts have the same stereochemistry of biologically active oxindole alkaloids, such as strychnofoline

Structural and biochemical evaluation of bisubstrate inhibitors of protein arginine N-methyltransferases PRMT1 and CARM1 (PRMT4)

Attenuating the function of protein arginine methyltransferases (PRMTs) is an objective for the investigation and treatment of several diseases including cardiovascular disease and cancer. Bisubstrate inhibitors that simultaneously target binding sites for arginine substrate and the co-factor (S-adenosylmethionine (SAM)) have potential utility, but structural information on their binding is required for their development. Evaluation of bisubstrate inhibitors featuring an isosteric guanidine replacement with two prominent enzymes PRMT1 and CARM1 (PRMT4) by isothermal titration calorimetry (ITC), activity assays and crystallography are reported. Key findings are that 2-aminopyridine is a viable replacement for guanidine, providing an inhibitor that binds more strongly to CARM1 than PRMT1. Moreover, a residue around the active site that differs between CARM1 (Asn-265) and PRMT1 (Tyr-160) is identified that affects the side chain conformation of the catalytically important neighbouring glutamate in the crystal structures. Mutagenesis data supports its contribution to the difference in binding observed for this inhibitor. Structures of CARM1 in complex with a range of seven inhibitors reveal the binding modes and show that inhibitors with an amino acid terminus adopt a single conformation whereas the electron density for equivalent amine-bearing inhibitors is consistent with preferential binding in two conformations. These findings inform the molecular basis of CARM1 ligand binding and identify differences between CARM1 and PRMT1 that can inform drug discovery efforts

Alterations in endogenous progesterone metabolism associated with spontaneous very preterm delivery

Study question: Do maternal serum levels of progesterone metabolites early in pregnancy correspond to an increased risk for very preterm delivery prior to 32 weeks? Summary answer: Maternal serum levels of 11-deoxycorticosterone (DOC) measured during the late first trimester or early second trimester correlate with an increased risk for preterm delivery prior to 32 weeks, and the correlation becomes stronger when the ratio of DOC to 16-alpha-hydroxyprogesterone was measured. What is known already: Progesterone is a pro-gestational steroid hormone that has been shown to decrease the risk of preterm birth in some pregnant women. Progesterone is metabolized by the body into various metabolites including members of the mineralocorticoid and glucocorticoid families. Our group has previously demonstrated that some progesterone metabolites enhance myometrial contractility in an ex vivo system, while others result in myometrial relaxation. The current exploratory study was designed to determine if pre-specified metabolites of progesterone measured early in pregnancy were associated with a woman's risk for delivery prior to 32 weeks, which is referred to as a very preterm delivery. Study design size duration: The Building Blocks of Pregnancy Biobank (BBPB) is a biorepository at Indiana University (IU) that follows women prospectively through their pregnancy. A variety of biospecimens are collected at various time points during a woman's pregnancy. Women participating in the IU BBPB who were enrolled after 8 weeks' gestation with pregnancy outcome data were eligible for participation. Participants/materials setting methods: Women delivering prior to 37 weeks (preterm) and at or after 37 weeks (term) who had blood samples collected during the late first trimester/early second trimester and/or during the early third trimester were identified. These samples were then processed for mass spectroscopy, and the amount of progesterone and progesterone metabolites in the samples were measured. Mean values of each measured steroid metabolite were calculated and compared among women delivering at less than 32 weeks, less than 37 weeks and greater than or equal to 37 weeks. Receiver operating characteristic (ROC) curves were constructed and threshold levels determined for each compound to identify a level above or below which best predicted a woman's risk for delivery prior to 32 and prior to 37 weeks. Mann-Whitney U nonparametric testing with Holm-Bonferroni correction for multiple comparisons was utilized to identify steroid ratios that could differentiate women delivering spontaneously at less than 32 weeks from all other pregnancies. Main results and the role of chance: Steroid hormone levels and pregnancy outcome data were available for 93 women; 28 delivering prior to 32 weeks, 40 delivering between 32 0/7 and 36 6/7 weeks and 25 delivering at or greater than 37 weeks: the mean gestational age at delivery within the three groups was 27.0, 34.4 and 38.8 weeks, respectively. Among women delivering spontaneously at less than 37 weeks, maternal 11-deoxycorticosterone (DOC) levels drawn in the late first trimester/early second trimester were significantly associated with spontaneous preterm delivery prior to 32 weeks; a threshold level of 47.5 pg/ml had 78% sensitivity, 73% specificity and an AUC of 0.77 (P = 0.044). When DOC levels were analyzed as a ratio with other measured steroid hormones, the ratio of DOC to 16-alpha-hydroxyprogesterone among women delivering spontaneously prior to 37 weeks was able to significantly discriminate women delivering prior to 32 weeks from those delivering at or greater than 32 weeks, with a threshold value of 0.2 with 89% sensitivity, 91% specificity and an AUC of 0.92 (P = 0.002). When the entire study cohort population was considered, including women delivering at term and women having an iatrogenic preterm delivery, the ratio of DOC to 16-alpha-hydroxyprogesterone was able to discriminate women delivering spontaneously prior to 32 weeks from the rest of the population at a threshold of 0.18 and 89% sensitivity, 59% specificity and an AUC of 0.81 (P = 0.003). Limitations reasons for caution: This is a discovery study, and the findings have not been validated on an independent cohort. To mitigate issues with multiple comparisons, we limited our study to pre-specified metabolites that are most representative of the major metabolic pathways for progesterone, and adjustments for multiple comparisons were made. Wider implications of the findings: Spontaneous preterm birth is increasingly being recognized to represent a common end pathway for a number of different disease phenotypes that include infection, inflammation, premature rupture of the membranes, uterine over distension, cervical insufficiency, placental dysfunction and genetic predisposition. In addition to these phenotypes, longitudinal changes in the maternal-fetal hypothalamic-pituitary-adrenal (HPA) axis also likely contribute to a significant proportion of the disease burden of spontaneous preterm birth. Here, we demonstrate that differential production of steroid metabolites is associated with very early preterm birth. The identified biomarkers may hint at a pathophysiologic mechanism and changes in the maternal-fetal dyad that result in preterm delivery. The early identification of abnormal changes in HPA axis metabolites may allow for targeted interventions that reverse the aberrant steroid metabolic profile to a more favorable one, thereby decreasing the risk for early delivery. Further research is therefore required to validate and extend the results presented here. Study funding/competing interests: Funding for this study was provided from the Office of the Vice Chancellor for Research at IUPUI, 'Funding Opportunities for Research Commercialization and Economic Success (FORCES) grant'.Both A.S.P. and C.A.G. are affiliated with Nixxi, a biotech startup. The remaining authors report no conflict of interest

Simple technique for evacuation of traumatic subcutaneous haematomas under tension

BACKGROUND: Traumatic subcutaneous haematomas are common cases in the accident and emergency department. Occasionally, urgent evacuation is required to prevent skin necrosis. METHODS: We present a simple and safe technique, based on a principle similar to liposuction to evacuate traumatic subcutaneous haematomas under tension. Instruments readily available in the accident and emergency department are used without the need of general anaesthesia. RESULTS: The technique was performed in six cases without complication such as infection or re-collection of the haematoma under tension. We present two typical scenarios where urgent evacuation was indicated and the technique performed. CONCLUSION: The technique is useful as an urgent and safe procedure in the accident and emergency department setting

A phase II experience with neoadjuvant irinotecan (CPT-11), 5-fluorouracil (5-FU) and leucovorin (LV) for colorectal liver metastases

<p>Abstract</p> <p>Background</p> <p>Chemotherapy may improve survival in patients undergoing resection of colorectal liver metastases (CLM). Neoadjuvant chemotherapy may help identify patients with occult extrahepatic disease (averting unnecessary metastasectomy), and it provides <it>in vivo </it>chemosensitivity data.</p> <p>Methods</p> <p>A phase II trial was initiated in which patients with resectable CLM received CPT-11, 5-FU and LV for 12 weeks. Metastasectomy was performed unless extrahepatic disease appeared. Postoperatively, patients with stable or responsive disease received the same regimen for 12 weeks. Patients with progressive disease received either second-line chemotherapy or best supportive care. The primary endpoint was disease-free survival (DFS); secondary endpoints included overall survival (OS) and safety.</p> <p>Results</p> <p>35 patients were accrued. During preoperative chemotherapy, 16 patients (46%) had grade 3/4 toxicities. Resection was not possible in 5 patients. One patient died of arrhythmia following surgery, and 1 patient had transient liver failure. During the postoperative treatment phase, 12 patients (55%) had grade 3/4 toxicities. Deep venous thrombosis (DVT) occurred in 11 patients (34%) at various times during treatment. Of those who underwent resection, median DFS was 23.0 mo. and median OS has not been reached. The overall survival from time of diagnosis of liver metastases was 51.6 mo for the entire cohort.</p> <p>Conclusion</p> <p>A short course of chemotherapy prior to hepatic metastasectomy may serve to select candidates best suited for resection and it may also direct postoperative systemic treatment. Given the significant incidence of DVT, alternative systemic neoadjuvant regimens should be investigated, particularly those that avoid the use of a central venous line.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov NCT00168155.</p

Reanalysis of Data Taken by the CANGAROO 3.8 Meter Imaging Atmospheric Cherenkov Telescope: PSR B1706-44, SN 1006, and Vela

We have reanalyzed data from observations of PSR B1706-44, SN 1006, and the Vela pulsar region made with the CANGAROO 3.8 m imaging atmospheric Cherenkov telescope between 1993 and 1998 in response to the results reported for these sources by the H.E.S.S. collaboration. In our reanalysis, in which gamma-ray selection criteria have been determined exclusively using gamma-ray simulations and OFF-source data as background samples, no significant TeV gamma-ray signals have been detected from compact regions around PSR B1706-44 or within the northeast rim of SN 1006. We discuss reasons why the original analyses gave the source detections. The reanalysis did result in a TeV gamma-ray signal from the Vela pulsar region at the 4.5 sigma level using 1993, 1994, and 1995 data. The excess was located at the same position, 0.13 deg. to the southeast of the Vela pulsar, as that reported in the original analysis. We have investigated the effect of the acceptance distribution in the field of view of the 3.8 m telescope, which rapidly decreases toward the edge of the field of the camera, on the detected gamma-ray morphology. The expected excess distribution for the 3.8 m telescope has been obtained by reweighting the distribution of HESS J0835-455 measured by H.E.S.S. with the acceptance of the 3.8 m telescope. The result is morphologically comparable to the CANGAROO excess distribution, although the profile of the acceptance-reweighted H.E.S.S. distribution is more diffuse than that of CANGAROO. The integral gamma-ray flux from HESS J0835-455 has been estimated for the same region as defined by H.E.S.S. from the 1993-1995 data of CANGAROO to be F(> 4.0 +/- 1.6 TeV) = (3.28 +/- 0.92) x 10^{-12} photons cm^{-2} s^{-1}, which is statistically consistent with the integral flux obtained by H.E.S.S.Comment: Published in ApJ, minor improvement

Lessons from Love-Locks: The archaeology of a contemporary assemblage

This document is the Accepted Manuscript version. The final, definitive version of this paper has been published in Journal of Material Culture, November 2017, published by SAGE Publishing, All rights reserved.Loss of context is a challenge, if not the bane, of the ritual archaeologist’s craft. Those who research ritual frequently encounter difficulties in the interpretation of its often tantalisingly incomplete material record. Careful analysis of material remains may afford us glimpses into past ritual activity, but our often vast chronological separation from the ritual practitioners themselves prevent us from seeing the whole picture. The archaeologist engaging with structured deposits, for instance, is often forced to study ritual assemblages post-accumulation. Many nuances of its formation, therefore, may be lost in interpretation. This paper considers what insights an archaeologist could gain into the place, people, pace, and purpose of deposition by recording an accumulation of structured deposits during its formation, rather than after. To answer this, the paper will focus on a contemporary depositional practice: the love-lock. This custom involves the inscribing of names/initials onto a padlock, its attachment to a bridge or other public structure, and the deposition of the corresponding key into the water below; a ritual often enacted by a couple as a statement of their romantic commitment. Drawing on empirical data from a three-year diachronic site-specific investigation into a love-lock bridge in Manchester, UK, the author demonstrates the value of contemporary archaeology in engaging with the often enigmatic material culture of ritual accumulations.Peer reviewe