Emergence and pathogenicity of highly virulent Cryptococcus gattii genotypes in the northwest United States.

Cryptococcus gattii causes life-threatening disease in otherwise healthy hosts and to a lesser extent in immunocompromised hosts. The highest incidence for this disease is on Vancouver Island, Canada, where an outbreak is expanding into neighboring regions including mainland British Columbia and the United States. This outbreak is caused predominantly by C. gattii molecular type VGII, specifically VGIIa/major. In addition, a novel genotype, VGIIc, has emerged in Oregon and is now a major source of illness in the region. Through molecular epidemiology and population analysis of MLST and VNTR markers, we show that the VGIIc group is clonal and hypothesize it arose recently. The VGIIa/IIc outbreak lineages are sexually fertile and studies support ongoing recombination in the global VGII population. This illustrates two hallmarks of emerging outbreaks: high clonality and the emergence of novel genotypes via recombination. In macrophage and murine infections, the novel VGIIc genotype and VGIIa/major isolates from the United States are highly virulent compared to similar non-outbreak VGIIa/major-related isolates. Combined MLST-VNTR analysis distinguishes clonal expansion of the VGIIa/major outbreak genotype from related but distinguishable less-virulent genotypes isolated from other geographic regions. Our evidence documents emerging hypervirulent genotypes in the United States that may expand further and provides insight into the possible molecular and geographic origins of the outbreak.

The Emergence of Access Controls in Small-Scale Fishing Commons: A Comparative Analysis of Individual Licenses and Common Property-Rights in Two Mexican Communities

Addressing global fisheries overexploitation requires better understanding of how small-scale fishing communities in developing countries limit access to fishing grounds. We analyze the performance of a system based on individual licenses and a common property-rights regime in their ability to generate incentives for self-governance and conservation of fishery resources. Using a qualitative before-after-control-impact approach, we compare two neighbouring fishing communities in the Gulf of California, Mexico. Both were initially governed by the same permit system, are situated in the same ecosystem, use similar harvesting technology, and have overharvested similar species. One community changed to a common property-right regime, enabling the emergence of access controls and avoiding overexploitation of benthic resources, while the other community, still relies on the permit system. We discuss the roles played by power, institutions, socio-historic, and biophysical factors to develop access controls. © 2012 The Author(s).

Design and Emergence in the Making of American Grand Strategy

The main research question of this thesis is how do grand strategies form. Grand strategy is defined as a state's coherent and consistent pattern of behavior over a long period of time in search of an overarching goal. The political science literature usually explains the formation of grand strategies by using a planning (or design) model. In this dissertation, I use primary sources, interviews with former government officials, and historical scholarship to show that the formation of grand strategy is better understood using a model of emergent learning imported from the business world. My two case studies examine the formation of American grand strategy during the Cold War and the post-Cold War eras. The dissertation concludes that in both these strategic eras the dominating grand strategies were formed primarily by emergent learning rather than flowing from advanced designs.

Structured Illumination Microscopy and a Quantitative Image Analysis for the Detection of Positive Margins in a Pre-Clinical Genetically Engineered Mouse Model of Sarcoma.

Intraoperative assessment of surgical margins is critical to ensuring residual tumor does not remain in a patient. Previously, we developed a fluorescence structured illumination microscope (SIM) system with a single-shot field of view (FOV) of 2.1 × 1.6 mm (3.4 mm2) and sub-cellular resolution (4.4 μm). The goal of this study was to test the utility of this technology for the detection of residual disease in a genetically engineered mouse model of sarcoma. Primary soft tissue sarcomas were generated in the hindlimb and after the tumor was surgically removed, the relevant margin was stained with acridine orange (AO), a vital stain that brightly stains cell nuclei and fibrous tissues. The tissues were imaged with the SIM system with the primary goal of visualizing fluorescent features from tumor nuclei. Given the heterogeneity of the background tissue (presence of adipose tissue and muscle), an algorithm known as maximally stable extremal regions (MSER) was optimized and applied to the images to specifically segment nuclear features. A logistic regression model was used to classify a tissue site as positive or negative by calculating area fraction and shape of the segmented features that were present and the resulting receiver operator curve (ROC) was generated by varying the probability threshold. Based on the ROC curves, the model was able to classify tumor and normal tissue with 77% sensitivity and 81% specificity (Youden's index). For an unbiased measure of the model performance, it was applied to a separate validation dataset that resulted in 73% sensitivity and 80% specificity. When this approach was applied to representative whole margins, for a tumor probability threshold of 50%, only 1.2% of all regions from the negative margin exceeded this threshold, while over 14.8% of all regions from the positive margin exceeded this threshold.

Accounting for Posttraumatic Stress Disorder Symptom Severity With Pre- and Posttrauma Measures: A Longitudinal Study of Older Adults.

Using data from a longitudinal study of community-dwelling older adults, we analyzed the most extensive set of known correlates of PTSD symptoms obtained from a single sample to examine the measures' independent and combined utility in accounting for PTSD symptom severity. Fifteen measures identified as PTSD risk factors in published meta-analyses and 12 theoretically and empirically supported individual difference and health-related measures were included. Individual difference measures assessed after the trauma, including insecure attachment and factors related to the current trauma memory, such as self-rated severity, event centrality, frequency of involuntary recall, and physical reactions to the memory, accounted for symptom severity better than measures of pre-trauma factors. In an analysis restricted to prospective measures assessed before the trauma, the total variance explained decreased from 56% to 16%. Results support a model of PTSD in which characteristics of the current trauma memory promote the development and maintenance of PTSD symptoms.