Bacterial Community Succession, Transmigration, and Differential Gene Transcription in a Controlled Vertebrate Decomposition Model

Decomposing remains are a nutrient-rich ecosystem undergoing constant change due to cell breakdown and abiotic fluxes, such as pH level and oxygen availability. These environmental fluxes affect bacterial communities who respond in a predictive manner associated with the time since organismal death, or the postmortem interval (PMI). Profiles of microbial taxonomic turnover and transmigration are currently being studied in decomposition ecology, and in the field of forensic microbiology as indicators of the PMI. We monitored bacterial community structural and functional changes taking place during decomposition of the intestines, bone marrow, lungs, and heart in a highly controlled murine model. We found that organs presumed to be sterile during life are colonized by Clostridium during later decomposition as the fluids from internal organs begin to emulsify within the body cavity. During colonization of previously sterile sites, gene transcripts for multiple metabolism pathways were highly abundant, while transcripts associated with stress response and dormancy increased as decomposition progressed. We found our model strengthens known bacterial taxonomic succession data after host death. This study is one of the first to provide data of expressed bacterial community genes, alongside transmigration and structural changes of microbial species during laboratory controlled vertebrate decomposition. This is an important dataset for studying the effects of the environment on bacterial communities in an effort to determine which bacterial species and which bacterial functional pathways, such as amino acid metabolism, provide key changes during stages of decomposition that relate to the PMI. Finding unique PMI species or functions can be useful for determining time since death in forensic investigations

Safety and Usage of C1-Inhibitor in Hereditary Angioedema: Berinert Registry Data

BackgroundThe plasma-derived, highly purified, nanofiltered C1-inhibitor concentrate (Berinert; “pnfC1-INH”) is approved in the United States for treating hereditary angioedema (HAE) attacks and in many European countries for attack treatment and short-term prophylaxis.ObjectiveThe objective of this study was to describe safety and usage patterns of pnfC1-INH.MethodsA multicenter, observational, registry was conducted between 2010 and 2014 at 30 United States and 7 European sites to obtain both prospective (occurring after enrollment) and retrospective (occurring before enrollment) safety and usage data on subjects receiving pnfC1-INH for any reason.ResultsOf 343 enrolled patients, 318 received 1 or more doses of pnfC1-INH for HAE attacks (11,848 infusions) or for prophylaxis (3142 infusions), comprising the safety population. Median dosages per infusion were 10.8 IU/kg (attack treatment) and 16.6 IU/kg (prophylaxis). Approximately 95% of infusions were administered outside of a health care setting. No adverse events (AEs) were reported in retrospective data. Among prospective data (n = 296 subjects; 9148 infusions), 252 AEs were reported in 85 (28.7%) subjects (rate of 0.03 events/infusion); 9 events were considered related to pnfC1-INH. Two thromboembolic events were reported in subjects with thrombotic risk factors. No patient was noted to have undergone viral testing for suspected blood-borne infection during registry participation.ConclusionsThe findings from this large, international patient registry documented widespread implementation of pnfC1-INH self-administration outside of a health care setting consistent with current HAE guidelines. These real-world data revealed pnfC1-INH usage for a variety of reasons in patients with HAE and showed a high level of safety regardless of administration setting or reason for use

IS LEGITIMACY CONTAGIOUS? THE COLLECTIVE LEGITIMATION OF ALTERNATIVE THERAPIES IN THE U.S. HOSPITAL INDUSTRY

Committee members: Pamela Tolbert (Chair) David Strang Wesley SineThis dissertation research examines the rise and spread of alternative medicine in the U.S. health care field. Alternative medicine includes a variety of treatment therapies (e.g., acupuncture, therapeutic touch, acupressure, etc.) whose underlying principles rest uneasily with those of dominant mainstream medicine. Although their efficacy is still subject to challenge by the medical establishment, these therapies have enjoyed increasing public acceptance in the last two decades, and recently a number of hospitals have begun to incorporate them into their formal structure. In this context, I explore an under-theorized process, the contagion of legitimacy among practices--how the adoption of one or more therapies by a given hospital affects the adoption of other alternative therapies by other hospitals. I suggest that the spread of one practice can be regarded as an informational cue on which potential adopters rely in deciding whether to adopt other associated practices. As long as the informational cue enhances the familiarity and acceptability of new practices, this type of influence may be understood as the process in which the legitimacy of some practices is transferred to other associated practices. As an underpinning process of such association, I focus on categorization which lumps similar practices into a common category and thus creates a common identity for the grouped practices. I argue that a categorical scheme serves as a cognitive basis for association between practices that would otherwise be viewed as disconnected. I empirically examine if the adoption of members of one group of alternative therapies accounts for variation in adoption rates of other therapies which are also in the same group. The findings of analyses strongly support my argument that prior adoptions of alternative therapies by hospitals enhance diffusion rates of other therapies, especially when the therapies present a coherent categorical identity. This study concludes with theoretical implications of the empirical findings and directions for future research