From camps to communities: Neets'ąįį Gwich'in planning and development in a pre- and post-settlement context

Thesis (Ph.D.) University of Alaska Fairbanks, 2018This study focuses on the Neets'aii Gwich'in, whose traditional territory is located in the northeastern interior of Alaska, and their experiences with planning and development. Prior to settling into permanent villages, the Neets'ąįį lived in widely scattered camps moving in relation to seasonal subsistence resources. Equipped with extensive knowledge of their country, Neets'ąįį people knew at any given time where the best places for certain animals and resources were and thus would camp closer to those areas. According to Neets'ąįį oral history, life in the "those days" was preoccupied with basic survival. Planning ahead, being prepared, and adapting to changing conditions were some of the key strategies that enabled the Neets'ąįį to survive from one generation to the next in one of the harshest climates in the world. The past 170 years has brought unprecedented change to the Neets'ąįį. The socio-economic and political context which historically defined the experience of the Neets'ąįį shifted dramatically as a result of colonization, the establishment of permanent settlements and the ensuing need for community infrastructure. Today, the Neets'ąįį are centralized in two villages, Vashrąįį K'ǫǫ (Arctic Village) and Vįįhtąįį (Venetie), located within the boundaries of the 1.8 million-acre Venetie Indian Reserve. The transition from Neets'ąįį camps to permanent communities has introduced many new needs including landfills, roads, power generation, etc. Whereas Neets'ąįį ancestors traditionally used planning as a survival strategy, their descendants today use planning to attract external investment for much needed infrastructure. This dissertation explores the ways in which the Neets'ąįį Gwich'in have engaged in planning and development in a pre- and post-settlement context

New insights into the genetic etiology of Alzheimer’s disease and related dementias

Characterization of the genetic landscape of Alzheimer’s disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/‘proxy’ AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Health-status outcomes with invasive or conservative care in coronary disease

BACKGROUND In the ISCHEMIA trial, an invasive strategy with angiographic assessment and revascularization did not reduce clinical events among patients with stable ischemic heart disease and moderate or severe ischemia. A secondary objective of the trial was to assess angina-related health status among these patients. METHODS We assessed angina-related symptoms, function, and quality of life with the Seattle Angina Questionnaire (SAQ) at randomization, at months 1.5, 3, and 6, and every 6 months thereafter in participants who had been randomly assigned to an invasive treatment strategy (2295 participants) or a conservative strategy (2322). Mixed-effects cumulative probability models within a Bayesian framework were used to estimate differences between the treatment groups. The primary outcome of this health-status analysis was the SAQ summary score (scores range from 0 to 100, with higher scores indicating better health status). All analyses were performed in the overall population and according to baseline angina frequency. RESULTS At baseline, 35% of patients reported having no angina in the previous month. SAQ summary scores increased in both treatment groups, with increases at 3, 12, and 36 months that were 4.1 points (95% credible interval, 3.2 to 5.0), 4.2 points (95% credible interval, 3.3 to 5.1), and 2.9 points (95% credible interval, 2.2 to 3.7) higher with the invasive strategy than with the conservative strategy. Differences were larger among participants who had more frequent angina at baseline (8.5 vs. 0.1 points at 3 months and 5.3 vs. 1.2 points at 36 months among participants with daily or weekly angina as compared with no angina). CONCLUSIONS In the overall trial population with moderate or severe ischemia, which included 35% of participants without angina at baseline, patients randomly assigned to the invasive strategy had greater improvement in angina-related health status than those assigned to the conservative strategy. The modest mean differences favoring the invasive strategy in the overall group reflected minimal differences among asymptomatic patients and larger differences among patients who had had angina at baseline

New insights into the genetic etiology of Alzheimer’s disease and related dementias

Characterization of the genetic landscape of Alzheimer’s disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/‘proxy’ AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele