Suicide among young Alaska Native men: community risk factors and alcohol control.

OBJECTIVES: I examined community risk factors that explained variation in suicide rates among young rural Alaska Native men, evaluating the effectiveness of local alcohol control as a public health policy to reduce this population's historically high vulnerability. METHODS: I compiled suicide data, alcohol control status, and community-level social, cultural, and economic characteristics for Alaska Native men aged 15 to 34 years in 178 small Alaska communities from 1980 to 2007. Poisson regression equations explained variation in suicide rates as a function of endogenous alcohol control and community characteristics. RESULTS: Suicide rates were higher in communities prohibiting alcohol importation under state law, but the effect was not significant after controlling for other community characteristics. More remote communities, those with fewer non-Natives, and those with evidence of cultural divides had higher suicide risks. Communities with higher incomes, more married couples, and traditional elders had lower risks. CONCLUSIONS: Alcohol control is ineffective in preventing suicide among Alaska Natives; suicide instead appears related to particular complex community characteristics that are either protective or increase risk. Communities have limited means to pursue economic and cultural development strategies that might offer more protection.

Chronic kidney disease and value-based care: Lessons from innovation, iteration, and ideation in primary care.

Value-based primary care has reduced health care costs, improved the quality of rendered care, and enhanced the patient experience. Value-based care emphasizes prevention, outreach, follow-up, patient engagement, and comprehensive, whole-person health. Primary care Accountable Care Organizations have leveraged technology-enabled workflows, practice transformation, and cutting-edge data and analytics to achieve success. These efforts are increasingly aided by predictive modeling used in the context of patient identification and prioritization algorithms. Value-based kidney care programs can glean salient takeaways from successful value-based primary care methods and models. The kidney care community is experiencing unprecedented transformation as novel payer programs and financial models burgeon. The authors contend these efforts can be accelerated by the adoption of techniques honed in value-based primary care. To optimize value-based kidney care, though, nephrology thought leaders must transcend the archetype of value-based primary care. To do so, the nephrology community must: (1) impel behavioral change among fee-for-service adherents; (2) harness emerging policy, guidelines, and quality measures; (3) adopt innovative tools, technologies, and therapies. In aggregating lessons from value-based primary care-and leveraging novel methodologies and approaches-the kidney care community will be better equipped to achieve the quadruple aim for kidney care.

Increasing multi-hazard climate risk and financial and health impacts on northern homeowners.

Currently, more than half of the world's human population lives in urban areas, which are increasingly affected by climate hazards. Little is known about how multi-hazard environments affect people, especially those living in urban areas in northern latitudes. This study surveyed homeowners in Anchorage and Fairbanks, USA, Alaska's largest urban centers, to measure individual risk perceptions, mitigation response, and damages related to wildfire, surface ice hazards, and permafrost thaw. Up to one third of residents reported being affected by all three hazards, with surface ice hazards being the most widely distributed, related to an estimated $25 million in annual damages. Behavioral risk response, policy recommendations for rapidly changing urban environments, and the challenges to local governments in mitigation efforts are discussed.

Global gateways as telecoupled human and natural systems: The emerging case of the Bering Strait.

Numerous narrow marine passages around the world serve as essential gateways for the transportation of goods, the movement of people, and the migration of fish and wildlife. These global gateways facilitate human-nature interactions across distant regions. The socioeconomic and environmental interactions among distant coupled human and natural systems affect the sustainability of global gateways in complex ways. However, the assessment and analysis of global gateways are scattered and fragmented. To fill this knowledge gap, we frame global gateways as telecoupled human and natural systems using an emerging global gateway, the Bering Strait, as a demonstration. We examine how three telecoupling processes (tourism, vessel traffic, and natural resource development) impact and are impacted by the coupled human and natural system of the Bering Strait Region. Given that global gateways share many similarities, our analysis of the Bering Strait Region provides a foundation for the assessment of other telecoupled global gateways.

Targeting Piezo1 unleashes innate immunity against cancer and infectious disease.

Piezo1 is a mechanosensitive ion channel that has gained recognition for its role in regulating diverse physiological processes. However, the influence of Piezo1 in inflammatory disease, including infection and tumor immunity, is not well studied. We postulated that Piezo1 links physical forces to immune regulation in myeloid cells. We found signal transduction via Piezo1 in myeloid cells and established this channel as the primary sensor of mechanical stress in these cells. Global inhibition of Piezo1 with a peptide inhibitor was protective against both cancer and septic shock and resulted in a diminution in suppressive myeloid cells. Moreover, deletion of Piezo1 in myeloid cells protected against cancer and increased survival in polymicrobial sepsis. Mechanistically, we show that mechanical stimulation promotes Piezo1-dependent myeloid cell expansion by suppressing the retinoblastoma gene Rb1 We further show that Piezo1-mediated silencing of Rb1 is regulated via up-regulation of histone deacetylase 2. Collectively, our work uncovers Piezo1 as a targetable immune checkpoint that drives immunosuppressive myelopoiesis in cancer and infectious disease.

NLRP3 signaling drives macrophage-induced adaptive immune suppression in pancreatic carcinoma.

The tumor microenvironment (TME) in pancreatic ductal adenocarcinoma (PDA) is characterized by immune tolerance, which enables disease to progress unabated by adaptive immunity. However, the drivers of this tolerogenic program are incompletely defined. In this study, we found that NLRP3 promotes expansion of immune-suppressive macrophages in PDA. NLRP3 signaling in macrophages drives the differentiation of CD4+ T cells into tumor-promoting T helper type 2 cell (Th2 cell), Th17 cell, and regulatory T cell populations while suppressing Th1 cell polarization and cytotoxic CD8+ T cell activation. The suppressive effects of NLRP3 signaling were IL-10 dependent. Pharmacological inhibition or deletion of NLRP3, ASC (apoptosis-associated speck-like protein containing a CARD complex), or caspase-1 protected against PDA and was associated with immunogenic reprogramming of innate and adaptive immunity within the TME. Similarly, transfer of PDA-entrained macrophages or T cells from NLRP3-/- hosts was protective. These data suggest that targeting NLRP3 holds the promise for the immunotherapy of PDA.

Flight safety in Alaska: comparing attitudes and practices of high- and low-risk air carriers.

INTRODUCTION: Aircraft operations are a vital component of the transportation system in Alaska. Between 1990-2002, a total of 481 people died in Alaska in aviation accidents. The purpose of this study was to examine the practices and attitudes of Alaska commuter and air taxi operators and their pilots as they relate to company fatal accident rates. METHODS: A case-control analysis based on accident statistics was performed, grouping operators and their pilots into cases and controls, based on operator fatal accident rates, during January 1990 to June 2001. Responses from two aviation safety surveys-one of air carrier operators and one of active commercial pilots-were compared between cases and controls. RESULTS: The average case pilot had less career flight experience than control pilots and worked 13 h x d(-1) and 81 h x wk(-10; that is, 1 h x d(-1) and 10 h wk-1 more than controls. Case operators were less likely to consider pilot fatigue a problem when scheduling flights (p = 0.05) and more likely to depend financially on timely delivery of bypass mail (p = 0.04). Case pilots were three times as likely as controls to fly daily into unknown weather conditions. Nearly 90% of case pilots reported that they never flew when so fatigued that they wanted to decline the flight, compared with 64% of control pilots (p = 0.01). CONCLUSIONS: Pilots of high-risk operators differed from those working for the other operators, both in experience and working conditions. The combination of pilot inexperience and longer work hours and workweeks may contribute to Alaska's high aviation crash rate.

The effect of regular primary care utilization on long-term glycemic and blood pressure control in adults with diabetes.

PURPOSE: Complications of diabetes mellitus (DM) can be reduced with regular preventive care and guidance on self-management. We investigated whether regular primary care utilization could improve glycemic control and blood pressure control among American Indian/Alaska Native people with DM. METHODS: Patient characteristics, risk factors, and health outcomes were identified from electronic health records of a cohort of 2138 adults with DM who received care between 1995 and 2010 from Southcentral Foundation, a tribal provider. Bivariate probit regression models estimated the probability of glycemic control and blood pressure control as functions of regular primary care, risk factors, and access factors, while taking into account potential bias arising from voluntarily choosing to seek primary care services. RESULTS: Regular primary care was associated with an 89% increased likelihood of blood pressure control (95% confidence interval [CI], 59-118%) and 177% increased likelihood of glycemic control (95% CI, 123-222%). Increasing the distance by 10 miles to primary care services reduced the likelihood of regular primary care by 3.7% (95% CI, -2.9% to -4.6%). CONCLUSIONS: Regular primary care utilization over 16 years was associated with higher rates of blood pressure control and glycemic control for adults with DM. People living closer to primary care services had a better chance of improved outcomes.

Alaska air carrier operator and pilot safety practices and attitudes: a statewide survey.

INTRODUCTION: Aviation crashes are a leading cause of occupational fatalities in Alaska, with Alaskan pilots having nearly 100 times the fatality rate of U.S. workers overall. A survey was designed to study pilot and company practices and attitudes in order to develop intervention strategies that would reduce aviation fatalities. METHODS: Two surveys were administered: one of air carrier operators and one of active commercial pilots. Surveys from 153 air taxi and public-use operators were received at a 79% response rate. RESULTS: There are almost 2000 pilots employed in Alaska during peak season by air taxi operators and public agencies. Surveyed operators and pilots generally agreed that improved weather information and regional hazards training would be effective ways to prevent crashes. Operators were more in favor of operator financial incentives (p < 0.05) and better pre-employment hiring checks on pilots (p < 0.05) compared with pilots' survey responses. There were 48% of pilots of large operators and 73% of pilots of small operators who considered their jobs to be at least as safe as other jobs. CONCLUSIONS: The results of operator-pilot comparisons suggest that financial pressures on operators may influence their views on what measures would be effective in preventing crashes, and that Alaskan pilots underestimate their occupational fatality risk.

Technology and managed care: patient benefits of telemedicine in a rural health care network.

Rural health providers have looked to telemedicine as a technology to reduce costs. However, virtual access to physicians and specialists may alter patients' demand for face-to-face physician access. We develop a model of service demand under managed care, and apply the model to a telemedicine application in rural Alaska. Provider-imposed delays and patient costs were highly significant predictors of patient contingent choices in a survey of ENT clinic patients. The results suggest that telemedicine increased estimated patient benefits by about $40 per visit, and reduced patients' loss from rationing of access to physicians by about 20%.