Creek Corridors Of Commerce: Converging Empires, Cultural Arbitration, And The Recourse Of Gulf Coast Trade

Abstract: this dissertation seeks to interpret how the upper creeks used geographic corridors (i.e. rivers and overland paths) to the Gulf of Mexico to offset economic and military dominance from Carolina and Georgia during the eighteenth century. Not only did access to these channels assure their commercial and territorial integrity through the colonial and postcolonial periods, but they also facilitated and empowered specific lineages and factions among the creeks in general. These special interest groups presented a confusing array of political alignment and counter-alignment that permitted the creeks avenues to challenge the coercive effects of outside markets. This is not meant to suggest that the creeks operated on an equal playing field with colonizing powers (though they oftentimes held advantages), or were immune to entangling arrangements such as alluring debt-credit cycles, alcoholism, military conquest, resource scarcity, or political manipulation. Instead, the creeks demonstrated an acute awareness to changing circumstances and adjusted while still operating within a traditional cultural framework. Their willingness to engage outside markets in creatively fluid ways, frustrated colonizing powers eager to recruit their undivided loyalty. Conventionally termed the creek policy of neutrality was actually an intrinsic cultural characteristic that involved competing factions, families, and towns--each eagerly seeking their own respective beneficial interaction zones with outsiders. Contrary to some interpretations, creek neutrality was not a well-organized and executed inter-town policy initiative that sought commercial arrangements from multiple directions and sources, while simultaneously curbing Euro-American trade and territorial ambitions. Contrary evidence suggests that Euro-American efforts to effectively consolidate and manipulate trade and military alliances with these heterogeneous creek communities were instead complicated by the autonomy of town, faction, and lineal support structures that each vied for connections to advantageously located channels of commercial activity among the various competing nation-states that colonized their peripheries

Moncure/Haywood, Chatham County : a community diagnosis including secondary data analysis and qualitative data collection

Community health cannot be fully understood without considering the health of the individuals that make up that community and social and environmental health indicators. The Moncure/Haywood community in rural Southeastern Chatham County was examined through Community Diagnosis, a process that integrates quantitative and qualitative data to create a picture of the social, political, psychological, environmental and physical health of communities. Our findings create this document that may provide a tool to help the community in future organizing and developing endeavors. Four students from the Department of Health Behavior and Health Education at the University of North Carolina's School of Public Health were assigned the task of exploring the community health of Moncure/Haywood as a learning experience. The four students, Shelly Harris, Kevin Harrell, Katie McIntire, and Dawn Rogers, worked within the community from September 1998 until May 1999, compiling data and interacting with Moncure/Haywood community members with the assistance of a preceptor, Margaret Pollard, the Chatham County Commissioner. The community diagnosis process attempts to understand the community from an insider's perspective. In order to attain this perspective, the methodology acknowledges that health status cannot be determined by statistics alone. Community Diagnosis examines the strengths and resources available to a community while examining the needs and weaknesses. A simultaneous examination may result in matching needs with already available assets and preventing overlap and duplication of services. This document provides a starting point for community members to address needs and use available resources. The project began in the Fall of 1998 with the secondary data collection regarding the general and social health of the community. Statistics gathered include morbidity and mortality, economic and demographic information, and historical and cultural information. Due to the lack of specific data on Moncure/Haywood, information was collected from the 1990 United States Census for the block group that includes Moncure/Haywood. Chatham County statistics were used when block group level data was not available. These data were compared to county and state statistics as well as to government health goals. Sources for secondary data include Log Into North Carolina (LINC), United States Census of 1990, Chatham Community Health Improvement Project (CCHIP), various state and county web sites, and agents within the local community. The qualitative data collection process began simultaneously. Community windshield tours and informal interviews at local gathering spots provided a glimpse into the community life of Moncure/Haywood. One aspect of exploring and introducing ourselves to the community included attending church services and community events. Moncure/Haywood is rich in cultural and community resources, which aided our endeavor. The Moncure/Haywood community sits in the southeast corner of Chatham County bordered by the Deep and Haw Rivers and U.S. Highway One, which are vital resources for the community. Many towns are located within a fifteen-mile radius of the community including Pittsboro, Sanford and Apex. The Research Triangle Park, a major technical and research center, and Raleigh, the state capital, are within 30 miles. The residents of Moncure/Haywood enjoy a community with a long, rich history. Originally attracting farming settlers, Moncure/Haywood lured developers of railroad and industry due to the plentiful natural resources. Religion also played a major role in the development of the community and continues to be of great importance to community members. Moncure/Haywood is a small community with less than 1000 residents. The population is almost equally balanced between African-Americans and White, providing a more integrated feel to the community than other rural towns. The majority of community members own their homes and the unemployment rate is very low. Once a booming town, Moncure/Haywood is now a bedroom community that relies on local industries and larger towns for employment. Residents generally travel to neighboring towns for shopping and recreation. Elementary and middle school children attend Moncure Elementary, and the community’s high school age teens are bussed to Northwood High School in Pittsboro. Moncure/Haywood is unincorporated and has no formal governing body. As a result, all community decisions are made at the county level by elected county commissioners. The community has grappled with the issue of incorporation for many years. Although not all agree, most community members feel that incorporation would be good for the community because of increased access to services and the potential for further growth. Community members obtain health services from the Moncure Community Health Center as well as from providers in Pittsboro, Sanford, Chapel Hill and other neighboring towns. The community health center provides many services and many of the older community members utilize its services. Other services for the community include a mobile health unit, social services, and community organizations. Data collection also involved collecting qualitative data through interviews with community members and service providers. An interview guide was established providing a framework of questions and issues to be addressed with interviewees. Institutional Review Board approval was obtained, and interviews began in January 1999. Interviewees were recruited through the preceptor as well as through informal interviews at church services. Community members suggested other persons to interview that would help create a picture of Moncure/Haywood life. Twenty people were interviewed and emerging issues became apparent as to the assets and needs of Moncure/Haywood. Data from the interviews were and then coded and organized into chapters to demonstrate the concerns of the community. A synopsis of the data was presented to community members in a community meeting on March 20, 1999 in order to reflect our findings and to obtain feedback. The forum provided an avenue for new issues to emerge and to reach residents who had not been heard. The drug problem that has emerged within the past five years in Moncure/Haywood concerned almost every community member. The drug problem has led to increased crime in the community. Many felt that the drug problem is a direct result from the lack of recreation and youth activities for the community's children. With an increase in the number of juvenile arrests within the past five years, the secondary data support the problem among the community's youth. Some community members also felt that lack of police protection may contribute to this problem as well, but action has been taken to place a Chatham County Deputy within a satellite office in the community. Most residents see growth in Moncure/Haywood positively. Growth would increase the tax base and attract businesses to the area. Sanford has begun the construction of a regional airport within two miles of the community which may further development. Residents felt that more opportunities and an increase in services would benefit Moncure/Haywood. The need for the development of a sewer system in Moncure/Haywood would be exacerbated by growth in the community. Many residents expressed that a sewage system needed to be developed in the community in order to attract more businesses and developers. Many residents also felt that this may only be accomplished if the community was incorporated. The strong sense of community and community ties in Moncure/Haywood was heard throughout the interviews. Community members felt that in times of need the community would pull together and assist one another. Churches and relationships between neighbors provide a stable foundation for the community and often catalyze community organizing. These fundamental foundations make the community competent to approach the issues that concern the community and to derive solutions. There are several limitations to the community diagnosis process in Moncure/Haywood. A large portion of secondary data was collected from the 1990 census that may not represent the current population. Lack of data specific to Moncure/Haywood also limited the accuracy of secondary data. The referral process limited the accuracy of the qualitative data. Interviewees referred community members to us. Therefore, data collected may represent one side of community issues. Data may also have been limited by a lack of trust among community members. This community diagnosis process only allowed a limited amount of time to engage and get to know residents. This may have influenced the type of information they were willing to share with us. This Community Diagnosis identified the strengths and weaknesses of Moncure/Haywood. This process can provide community members with a starting place to address their needs and to aid in getting support or funding for potential services. By highlighting the resources already available to the community, community members can also examine what creative solutions may already exist and prioritize the issues at hand.Master of Public Healt

Inhibition of Respiration by Nitric Oxide Induces a Mycobacterium tuberculosis Dormancy Program

An estimated two billion persons are latently infected with Mycobacterium tuberculosis. The host factors that initiate and maintain this latent state and the mechanisms by which M. tuberculosis survives within latent lesions are compelling but unanswered questions. One such host factor may be nitric oxide (NO), a product of activated macrophages that exhibits antimycobacterial properties. Evidence for the possible significance of NO comes from murine models of tuberculosis showing progressive infection in animals unable to produce the inducible isoform of NO synthase and in animals treated with a NO synthase inhibitor. Here, we show that O2 and low, nontoxic concentrations of NO competitively modulate the expression of a 48-gene regulon, which is expressed in vivo and prepares bacilli for survival during long periods of in vitro dormancy. NO was found to reversibly inhibit aerobic respiration and growth. A heme-containing enzyme, possibly the terminal oxidase in the respiratory pathway, likely senses and integrates NO and O2 levels and signals the regulon. These data lead to a model postulating that, within granulomas, inhibition of respiration by NO production and O2 limitation constrains M. tuberculosis replication rates in persons with latent tuberculosis

Robust time-varying multivariate coherence estimation: Application to electroencephalogram recordings during general anesthesia

Coherence analysis characterizes frequency-dependent covariance between signals, and is useful for multivariate oscillatory data often encountered in neuroscience. The global coherence provides a summary of coherent behavior in high-dimensional multivariate data by quantifying the concentration of variance in the first mode of an eigenvalue decomposition of the cross-spectral matrix. Practical application of this useful method is sensitive to noise, and can confound coherent activity in disparate neural populations or spatial locations that have a similar frequency structure. In this paper we describe two methodological enhancements to the global coherence procedure that increase robustness of the technique to noise, and that allow characterization of how power within specific coherent modes change through time.National Institutes of Health (U.S.) (Grant DP2-OD006454)National Institutes of Health (U.S.) (Grant K25-NS057580)National Institutes of Health (U.S.) (Grant DP1-OD003646)National Institutes of Health (U.S.) (Grant R01-EB006385)National Institutes of Health (U.S.) (Grant R01-MH071847

The melanoma-specific graded prognostic assessment does not adequately discriminate prognosis in a modern population with brain metastases from malignant melanoma

The melanoma-specific graded prognostic assessment (msGPA) assigns patients with brain metastases from malignant melanoma to 1 of 4 prognostic groups. It was largely derived using clinical data from patients treated in the era that preceded the development of newer therapies such as BRAF, MEK and immune checkpoint inhibitors. Therefore, its current relevance to patients diagnosed with brain metastases from malignant melanoma is unclear. This study is an external validation of the msGPA in two temporally distinct British populations.Performance of the msGPA was assessed in Cohort I (1997-2008, n=231) and Cohort II (2008-2013, n=162) using Kaplan-Meier methods and Harrell's c-index of concordance. Cox regression was used to explore additional factors that may have prognostic relevance.The msGPA does not perform well as a prognostic score outside of the derivation cohort, with suboptimal statistical calibration and discrimination, particularly in those patients with an intermediate prognosis. Extra-cerebral metastases, leptomeningeal disease, age and potential use of novel targeted agents after brain metastases are diagnosed, should be incorporated into future prognostic models.An improved prognostic score is required to underpin high-quality randomised controlled trials in an area with a wide disparity in clinical care

Bayesian analysis of trinomial data in behavioral experiments and its application to human studies of general anesthesia

Accurate quantification of loss of response to external stimuli is essential for understanding the mechanisms of loss of consciousness under general anesthesia. We present a new approach for quantifying three possible outcomes that are encountered in behavioral experiments during general anesthesia: correct responses, incorrect responses and no response. We use a state-space model with two state variables representing a probability of response and a conditional probability of correct response. We show applications of this approach to an example of responses to auditory stimuli at varying levels of propofol anesthesia ranging from light sedation to deep anesthesia in human subjects. The posterior probability densities of model parameters and the response probability are computed within a Bayesian framework using Markov Chain Monte Carlo methods.National Institutes of Health (U.S.) (Grant DP2-OD006454)National Institutes of Health (U.S.) (Grant K25-NS057580)National Institutes of Health (U.S.) (Grant DP1-OD003646)National Institutes of Health (U.S.) (Grant R01-EB006385)National Institutes of Health (U.S.) (Grant R01-MH071847

Secondary somatic mutations restoring RAD51C and RAD51D associated with acquired resistance to the PARP inhibitor rucaparib in high-grade ovarian carcinoma

High-grade epithelial ovarian carcinomas (OC) containing mutated BRCA1 or BRCA2 (BRCA1/2) homologous recombination (HR) genes are sensitive to platinum-based chemotherapy and poly(ADP-ribose) polymerase inhibitors (PARPi), while restoration of HR function due to secondary mutations in BRCA1/2 has been recognized as an important resistance mechanism. We sequenced core HR pathway genes in 12 pairs of pre-treatment and post-progression tumor biopsy samples collected from patients in ARIEL2 Part 1, a phase 2 study of the PARPi rucaparib as treatment for platinum-sensitive, relapsed OC. In six of 12 pre-treatment biopsies, a truncation mutation in BRCA1, RAD51C or RAD51D was identified. In five of six paired post-progression biopsies, one or more secondary mutations restored the open reading frame. Four distinct secondary mutations and spatial heterogeneity were observed for RAD51C. In vitro complementation assays and a patient-derived xenograft (PDX), as well as predictive molecular modeling, confirmed that resistance to rucaparib was associated with secondary mutations

Differential neuromuscular training effects onACL injury risk factors in"high-risk" versus "low-risk" athletes

<p>Abstract</p> <p>Background</p> <p>Neuromuscular training may reduce risk factors that contribute to ACL injury incidence in female athletes. Multi-component, ACL injury prevention training programs can be time and labor intensive, which may ultimately limit training program utilization or compliance. The purpose of this study was to determine the effect of neuromuscular training on those classified as "high-risk" compared to those classified as "low-risk." The hypothesis was that high-risk athletes would decrease knee abduction moments while low-risk and control athletes would not show measurable changes.</p> <p>Methods</p> <p>Eighteen high school female athletes participated in neuromuscular training 3×/week over a 7-week period. Knee kinematics and kinetics were measured during a drop vertical jump (DVJ) test at pre/post training. External knee abduction moments were calculated using inverse dynamics. Logistic regression indicated maximal sensitivity and specificity for prediction of ACL injury risk using external knee abduction (25.25 Nm cutoff) during a DVJ. Based on these data, 12 study subjects (and 4 controls) were grouped into the high-risk (knee abduction moment >25.25 Nm) and 6 subjects (and 7 controls) were grouped into the low-risk (knee abduction <25.25 Nm) categories using mean right and left leg knee abduction moments. A mixed design repeated measures ANOVA was used to determine differences between athletes categorized as high or low-risk.</p> <p>Results</p> <p>Athletes classified as high-risk decreased their knee abduction moments by 13% following training (Dominant pre: 39.9 ± 15.8 Nm to 34.6 ± 9.6 Nm; Non-dominant pre: 37.1 ± 9.2 to 32.4 ± 10.7 Nm; p = 0.033 training X risk factor interaction). Athletes grouped into the low-risk category did not change their abduction moments following training (p > 0.05). Control subjects classified as either high or low-risk also did not significantly change from pre to post-testing.</p> <p>Conclusion</p> <p>These results indicate that "high-risk" female athletes decreased the magnitude of the previously identified risk factor to ACL injury following neuromuscular training. However, the mean values for the high-risk subjects were not reduced to levels similar to low-risk group following training. Targeting female athletes who demonstrate high-risk knee abduction loads during dynamic tasks may improve efficacy of neuromuscular training. Yet, increased training volume or more specific techniques may be necessary for high-risk athletes to substantially decrease ACL injury risk.</p

Combinations of Host Biomarkers Predict Mortality among Ugandan Children with Severe Malaria: A Retrospective Case-Control Study

Background: Severe malaria is a leading cause of childhood mortality in Africa. However, at presentation, it is difficult to predict which children with severe malaria are at greatest risk of death. Dysregulated host inflammatory responses and endothelial activation play central roles in severe malaria pathogenesis. We hypothesized that biomarkers of these processes would accurately predict outcome among children with severe malaria. Methodology/Findings: Plasma was obtained from children with uncomplicated malaria (n = 53), cerebral malaria (n = 44) and severe malarial anemia (n = 59) at time of presentation to hospital in Kampala, Uganda. Levels of angiopoietin-2, von Willebrand Factor (vWF), vWF propeptide, soluble P-selectin, soluble intercellular adhesion molecule-1 (ICAM-1), soluble endoglin, soluble FMS-like tyrosine kinase-1 (Flt-1), soluble Tie-2, C-reactive protein, procalcitonin, 10 kDa interferon gamma-induced protein (IP-10), and soluble triggering receptor expressed on myeloid cells-1 (TREM-1) were determined by ELISA. Receiver operating characteristic (ROC) curve analysis was used to assess predictive accuracy of individual biomarkers. Six biomarkers (angiopoietin-2, soluble ICAM-1, soluble Flt-1, procalcitonin, IP-10, soluble TREM-1) discriminated well between children who survived severe malaria infection and those who subsequently died (area under ROC curve&gt;0.7). Combinational approaches were applied in an attempt to improve accuracy. A biomarker score was developed based on dichotomization and summation of the six biomarkers, resulting in 95.7% (95% CI: 78.1-99.9) sensitivity and 88.8% (79.7-94.7) specificity for predicting death. Similar predictive accuracy was achieved with models comprised of 3 biomarkers. Classification tree analysis generated a 3-marker model with 100% sensitivity and 92.5% specificity (cross-validated misclassification rate: 15.4%, standard error 4.9%). Conclusions: We identified novel host biomarkers of pediatric severe and fatal malaria (soluble TREM-1 and soluble Flt-1) and generated simple biomarker combinations that accurately predicted death in an African pediatric population. While requiring validation in further studies, these results suggest the utility of combinatorial biomarker strategies as prognostic tests for severe malaria

The Fragmented Mitochondrial Ribosomal RNAs of Plasmodium falciparum

The mitochondrial genome in the human malaria parasite Plasmodium falciparum is most unusual. Over half the genome is composed of the genes for three classic mitochondrial proteins: cytochrome oxidase subunits I and III and apocytochrome b. The remainder encodes numerous small RNAs, ranging in size from 23 to 190 nt. Previous analysis revealed that some of these transcripts have significant sequence identity with highly conserved regions of large and small subunit rRNAs, and can form the expected secondary structures. However, these rRNA fragments are not encoded in linear order; instead, they are intermixed with one another and the protein coding genes, and are coded on both strands of the genome. This unorthodox arrangement hindered the identification of transcripts corresponding to other regions of rRNA that are highly conserved and/or are known to participate directly in protein synthesis.The identification of 14 additional small mitochondrial transcripts from P. falciparum and the assignment of 27 small RNAs (12 SSU RNAs totaling 804 nt, 15 LSU RNAs totaling 1233 nt) to specific regions of rRNA are supported by multiple lines of evidence. The regions now represented are highly similar to those of the small but contiguous mitochondrial rRNAs of Caenorhabditis elegans. The P. falciparum rRNA fragments cluster on the interfaces of the two ribosomal subunits in the three-dimensional structure of the ribosome.All of the rRNA fragments are now presumed to have been identified with experimental methods, and nearly all of these have been mapped onto the SSU and LSU rRNAs. Conversely, all regions of the rRNAs that are known to be directly associated with protein synthesis have been identified in the P. falciparum mitochondrial genome and RNA transcripts. The fragmentation of the rRNA in the P. falciparum mitochondrion is the most extreme example of any rRNA fragmentation discovered