This dissertation defines “amateurism” to include a characteristic set of beliefs, a body of knowledge, and a way of knowing, all organized around the principle that it is possible, and perhaps preferable, to play music without established musical knowledge. I investigate how musicians confront hierarchies, both political and epistemological, with an amateurist insistence on their ability to perform without established knowledge. Typically, established musical knowledge conforms to standards and norms of technique, training, or education, which enact a powerful regulation of musical cultures. Through my research, I found that musicians who appear to lack or reject musical knowledge entirely nevertheless rely upon a wealth of subjugated epistemes and that every musical performance draws upon some type of knowledge. I examine four examples of musical amateurism from London and New York City in the 1970s in order to describe the use of amateurism as a political tool to critique epistemological hierarchies. Each example highlights musicians who articulated participation as a central tenant of their alternative episteme, in contrast to established musical knowledge. Each example highlights musicians who articulated participation as a central tenant of their alternative episteme, in contrast to established musical knowledge: 1) Cornelius Cardew’s attempt to create an anti-hierarchical experimental ensemble (Scratch Orchestra) that united skilled composers and untrained amateurs; 2) the widely-accepted claim that the Sex Pistols, and punks generally, could not play their instruments; 3) how “no wave” musicians, including Lydia Lunch, drew on supposedly instinctual performance practices to supplant technical instrumental skills; and 4) how amateurism became racialized as “primitive” when white downtown musicians confronted black rap musicians from Harlem and the Bronx. Whether these musicians were authentically able to disestablish hierarchies, or whether they merely re-codified their bodies of knowledge, depends on whether one wants to give a reading that gives undue force to the political possibility of musical amateurism. I argue that these performers’ appeals to musical amateurism effectively upset prevailing notions of musical knowledge in the 1970s, even if they themselves were limited in their ability to reconfigure power structures.

For precision oncology to become a reality, clinicians need access to tumor tissue in a real-time, repeatable, and cost-effective manner. Circulating tumor cells (CTCs), cells of tumor origin that circulate in the blood, are one possible solution, with the potential to serve as a “liquid biopsy” for gastrointestinal (GI) tumors.

In this thesis, we demonstrate the development and validation of an assay for performing molecular analysis of CTCs as a biomarker for GI cancers. We used a microfluidic platform to develop GI tumor-specific CTC assays for pancreatic and liver cancer through incorporation of tissue-specific markers for CTC capture and identification. We then conducted prospective studies testing the utility of CTC enumeration as a biomarker in pancreatic (n=100) and liver (n=61) cancer. We found that the use of a tissue-specific assay resulted in higher CTC counts than in previous studies, that CTC counts correlated with increasing stage and that CTC enumeration may have diagnostic and prognostic utility as a biomarker in GI cancers.

Using a modified assay that allows for the complete isolation of the CTCs identified, we confirmed the tumor origin of the CTCs we identified by comparison of mutational status with the primary tumor using both Sanger and next generation sequencing methods.

After confirming their tumor origin, we developed a quality control assay that allowed us to determine how many CTCs we would need to isolate to reliably perform CTC molecular analysis. Using this metric, we modified our CTC sequencing protocol that resulted in reliable sequencing from as few as 3-5 CTCs as opposed to the 10-20 needed using the traditional CTC sequencing protocol. We then used our optimized CTC sequencing protocol in a prospective study to test the feasibility and potential utility of CTC molecular analysis as a biomarker in liver cancer.

The research described in this thesis serves two primary goals. The first is as a validated method that allows for the use of CTCs in liquid biopsy-type applications for both HCC and PDAC patients. The second is as a framework for validating CTC assays and definitions to ensure the reliability and reproducibility of CTC sequencing results.

Road decommissioning is an increasingly important tool for restoring watersheds on national forest lands. Wildland roads can result in a number of negative impacts leading to decreased terrestrial and aquatic habitat quality. It is believed, therefore, that road decommissioning can have significant positive effects on a watershed—cleaner water, improved fisheries, and restored habitat for terrestrial animals. However, very little research has been conducted to quantify these benefits. In 1998, the Clearwater National Forest (CNF) and Nez Perce Tribe (NPT) began an intensive road decommissioning program after extensive flooding caused hundreds of landslides in 1995-1996. Since the program’s inception, more than 500 miles of roads have been decommissioned. Neither the CNF nor the NPT can sustain the budget and personnel necessary to monitor how effectively these projects are restoring fish and wildlife habitat. Data collected through a citizen monitoring program will fill this need. Citizen science is a popular and powerful way to monitor the long-term trends and conditions of natural systems while also encouraging a stewardship ethic for the resources being monitored. The information gathered by “citizen scientists” can help land managers make more informed decisions about how best to care for public and private land. We have created the first citizen monitoring program that focuses on the ecological recovery of decommissioned roads. We developed monitoring protocols for citizen scientists, recruited and trained volunteers, and led monitoring trips in the field every weekend during the summer and fall of 2005, engaging, thus far, some 20 volunteers. As this project is still in progress, all conclusions and findings reported are preliminary. We can, however, make general observations on the efficacy and accuracy of employing citizen scientists to measure ecosystem recovery as a result of road decommissioning. In addition, a second year of funding has been obtained for this project. We anticipate that next year’s program will be a success in forwarding our objectives for this project.