A CASE STUDY OF INDIVIDUAL AND ORGANIZATIONAL STAKEHOLDER PERSPECTIVES ON STATE FACTORS IMPACTING ACCESS TO RURAL HEALTH CARE SERVICES IN IDAHO

The purpose of this case study was to describe individual and organizational perspectives on the state factors and political context impacting access to rural health care services in Idaho. Approximately 50 million Americans, roughly 20% of the United States population, live in rural areas (U.S. Census Bureau, 2012). For over 100 years, U.S. rural residents have experienced health disparities and health care access barriers (De Alessi & Pam, 2011). Rural residents evidence greater health risks, fewer health care providers, poorer health outcomes, and greater mortality than most urban residents (Jones, Parker, Ahearn, Mishra, & Variyam, 2009). Since many rural health care policies are implemented at the state level, state-level factors, such as health care delivery systems and the political context of health care, influence policy outcomes and rural health care access (Gray & Hanson, 2004; Jacobs & Callaghan, 2013). Although state-level rural health care access barriers are well documented, these have not been studied qualitatively in relation to state political context. This case study employed narrative and thematic analyses to identify state-level factors and the political context that diverse stakeholders and interest groups perceive to impact rural health care access in Idaho. The study was developed from the analysis of twenty stakeholder interview transcripts and seven stakeholder group websites and the documents made publicly available on these websites. Stakeholders identified six state factors significantly impacting access to health care services in rural Idaho: the economy, rural/frontier geographic features, rural patient population, rural health care system, interest groups/policy voices, and the primary care provider shortage. Surprisingly, stakeholders only noted physicians as a solution to the workforce shortage, failing to mention nurse practitioners. Interest group websites and their associated documents illuminated four state factors related to the political context in Idaho: a narrative of state sovereignty, a narrative of medical sovereignty, the financial viability of health care in Idaho, and relationships of dependence and competition among key stakeholders. This case study poses questions to the profession of nursing about its priorities in developing an independent, compelling narrative to advance access to rural health care in and beyond Idaho

Diverse Stakeholder Perspectives on Rural Health Care Reform in a U.S. State that Rejected the Affordable Care Act: A Case Study

Purpose: This case study identifies rural health care stakeholder perspectives on the Affordable Care Act (ACA) and describes the health policy context in Idaho, the only state in the United States to reject Medicaid expansion yet develop a state-run health insurance exchange. Sample: The sample included 20 rural health care stakeholders, including clinicians, elected officials, state agency administrators, health care facility administrators, and interest group leaders. Method: A single-case study of stakeholder perspectives on the ACA and rural health care access in Idaho was conducted from 2014 to 2016. Data sources include qualitative interviews with 20 rural health care stakeholders and public documents relating to the ACA and rural health care from Idaho governmental and nongovernmental entities’ websites. Findings: Since the 2010 passage of the ACA, opposition to “Obamacare” became associated with a conservative stance on health care reform. However, in this case study, diverse health care stakeholders who criticized aspects of the ACA identified several components of the policy, including Medicaid expansion, as essential in ensuring access to rural health care. Some stakeholders called for federal legislation authorizing nurse practitioners to practice as independent primary care providers. However, the politics of medical sovereignty present challenges to this relevant strategy and to full implementation of Idaho’s Nurse Practice Act for increasing access to primary care in a rural state. Conclusions: The case study approach can be effective in illuminating stakeholder perspectives and policy strategies that may fall outside of polarized health care policy debates. Examination of the state-level political context of rural health care must consider concurrent battles about state sovereignty over health care policy and professional-clinical battles about sovereignty over primary care

A better climate for disaster risk management

Climate-related disasters are by far the most frequent natural disasters, exacting a heavy toll on people and economies. Their frequency and economic losses have steadily increased over the past few decades, stretching the response capacities of governments and humanitarian organizations. One of the many ways this challenge can be addressed is by making more effective use of the increasing wealth of climate information and tailoring it to the needs of those who could use it, to better predict and prepare for such disasters before they occur. Written in partnership with a range of humanitarian organizations, A Better Climate for Disaster Risk Management is the third in the Climate and Society Publication series. This issue highlights recent advances in the use of climate information to manage risks and improve livelihoods, such as new partnerships and user-designed information platforms. It draws together and analyzes experiences from 17 case studies that capture the current state of knowledge. It also highlights research innovations in technical boxes throughout the publication. A problem-solving framework is used to demonstrate the challenges and opportunities facing disaster risk managers in using climate science with a three step approach: identifying the problem, developing tools, and taking action, reflected in the chapter titles. The case studies and experiences presented in this book draw on a wealth of practical experience from within the humanitarian community. They acknowledge the enormous effort and investment by very many national and local governments, international organizations, and an increasing range of other actors in the field of climate information for disaster risk management. This publication adds to the growing body of knowledge, focusing on the experiences of a number of mostly non-governmental actors, especially the International Federation of Red Cross and Red Crescent Societies, and how through partnerships, they have helped to integrate state of the art climate science and information into improved decision-making. Exploring the use of climate information for disaster risk management, it identifies both the achievements and the obstacles associated with this endeavour. From them are distilled the lessons learned, and a series of recommendations. Of these, effective partnership is highlighted as the single most critical ingredient for success. Climate information that can be acted upon is best created in dialogue between the users and providers, and partnerships between climate scientists and disaster risk managers should promote knowledge sharing, trust, and the development of innovative solutions. Efforts to better apply climate information in disaster risk management should first focus on immediate opportunities and potential ‘quick wins’. Practical engagements can be fostered by initially concentrating on countries and regions with relatively good seasonal forecast skills, and where humanitarian decisions can be influenced to provide large and immediate returns on investment. Disaster risk managers must, however, improve their understanding of the potential as well as the limitations of climate information, as the development of realistic expectations is vital to maintaining trust in the information and those who provide it. Cases demonstrate that when climate information can be integrated into existing decision-making support tools or systems, it becomes an important piece of the information that is considered and taken up in the routine activities of disaster risk managers. The relative contribution that seasonal, decadal, and long-term trends make to current and future climate also needs to be better understood. To achieve the goal of providing relevant climate services to support disaster risk management, climate information providers such as national meteorological services must tailor their information to the problem at hand, either by refining products through iterative interaction with partners or by simplifying the presentation. Although there have been many achievements and advances, much potential remains to be realized. Herein lies the opportunity: to build trust and improve the sharing of knowledge between the providers of climate services, and those who can use those services to enhance disaster risk management, jointly reducing human suffering and achieving more sustainable development

Whole cell reconstructions of Leishmania mexicana through the cell cycle

The unicellular parasite Leishmania has a precisely defined cell architecture that is inherited by each subsequent generation, requiring a highly coordinated pattern of duplication and segregation of organelles and cytoskeletal structures. A framework of nuclear division and morphological changes is known from light microscopy, yet this has limited resolution and the intrinsic organisation of organelles within the cell body and their manner of duplication and inheritance is unknown. Using volume electron microscopy approaches, we have produced three-dimensional reconstructions of different promastigote cell cycle stages to give a spatial and quantitative overview of organelle positioning, division and inheritance. The first morphological indications seen in our dataset that a new cell cycle had begun were the assembly of a new flagellum, the duplication of the contractile vacuole and the increase in volume of the nucleus and kinetoplast. We showed that the progression of the cytokinesis furrow created a specific pattern of membrane indentations, while our analysis of sub-pellicular microtubule organisation indicated that there is likely a preferred site of new microtubule insertion. The daughter cells retained these indentations in their cell body for a period post-abscission. By comparing cultured and sand fly derived promastigotes, we found an increase in the number and overall volume of lipid droplets in the promastigotes from the sand fly, reflecting a change in their metabolism to ensure transmissibility to the mammalian host. Our insights into the cell cycle mechanics of Leishmania will support future molecular cell biology analyses of these parasites

Towards OPM-MEG in a virtual reality environment

Virtual reality (VR) provides an immersive environment in which a participant can experience a feeling of presence in a virtual world. Such environments generate strong emotional and physical responses and have been used for wide-ranging applications. The ability to collect functional neuroimaging data whilst a participant is immersed in VR would represent a step change for experimental paradigms; unfortunately, traditional brain imaging requires participants to remain still, limiting the scope of naturalistic interaction within VR. Recently however, a new type of magnetoencephalography (MEG) device has been developed, that employs scalp-mounted optically-pumped magnetometers (OPMs) to measure brain electrophysiology. Lightweight OPMs, coupled with precise control of the background magnetic field, enables participant movement during data acquisition. Here, we exploit this technology to acquire MEG data whilst a participant uses a virtual reality head-mounted display (VRHMD). We show that, despite increased magnetic interference from the VRHMD, we were able to measure modulation of alpha-band oscillations, and the visual evoked field. Moreover, in a VR experiment in which a participant had to move their head to look around a virtual wall and view a visual stimulus, we showed that the measured MEG signals map spatially in accordance with the known organisation of primary visual cortex. This technique could transform the type of neuroscientific experiment that can be undertaken using functional neuroimaging

Glycine supplementation extends lifespan of male and female mice.

Diets low in methionine extend lifespan of rodents, though through unknown mechanisms. Glycine can mitigate methionine toxicity, and a small prior study has suggested that supplemental glycine could extend lifespan of Fischer 344 rats. We therefore evaluated the effects of an 8% glycine diet on lifespan and pathology of genetically heterogeneous mice in the context of the Interventions Testing Program. Elevated glycine led to a small (4%-6%) but statistically significant lifespan increase, as well as an increase in maximum lifespan, in both males (p = 0.002) and females (p \u3c 0.001). Pooling across sex, glycine increased lifespan at each of the three independent sites, with significance at p = 0.01, 0.053, and 0.03, respectively. Glycine-supplemented females were lighter than controls, but there was no effect on weight in males. End-of-life necropsies suggested that glycine-treated mice were less likely than controls to die of pulmonary adenocarcinoma (p = 0.03). Of the 40 varieties of incidental pathology evaluated in these mice, none were increased to a significant degree by the glycine-supplemented diet. In parallel analyses of the same cohort, we found no benefits from TM5441 (an inhibitor of PAI-1, the primary inhibitor of tissue and urokinase plasminogen activators), inulin (a source of soluble fiber), or aspirin at either of two doses. Our glycine results strengthen the idea that modulation of dietary amino acid levels can increase healthy lifespan in mice, and provide a foundation for further investigation of dietary effects on aging and late-life diseases

Glycine supplementation extends lifespan of male and female mice.

Diets low in methionine extend lifespan of rodents, though through unknown mechanisms. Glycine can mitigate methionine toxicity, and a small prior study has suggested that supplemental glycine could extend lifespan of Fischer 344 rats. We therefore evaluated the effects of an 8% glycine diet on lifespan and pathology of genetically heterogeneous mice in the context of the Interventions Testing Program. Elevated glycine led to a small (4%-6%) but statistically significant lifespan increase, as well as an increase in maximum lifespan, in both males (p = 0.002) and females (p \u3c 0.001). Pooling across sex, glycine increased lifespan at each of the three independent sites, with significance at p = 0.01, 0.053, and 0.03, respectively. Glycine-supplemented females were lighter than controls, but there was no effect on weight in males. End-of-life necropsies suggested that glycine-treated mice were less likely than controls to die of pulmonary adenocarcinoma (p = 0.03). Of the 40 varieties of incidental pathology evaluated in these mice, none were increased to a significant degree by the glycine-supplemented diet. In parallel analyses of the same cohort, we found no benefits from TM5441 (an inhibitor of PAI-1, the primary inhibitor of tissue and urokinase plasminogen activators), inulin (a source of soluble fiber), or aspirin at either of two doses. Our glycine results strengthen the idea that modulation of dietary amino acid levels can increase healthy lifespan in mice, and provide a foundation for further investigation of dietary effects on aging and late-life diseases

Late-Stage Metastatic Melanoma Emerges through a Diversity of Evolutionary Pathways

Understanding the evolutionary pathways to metastasis and resistance to immune-checkpoint inhibitors (ICI) in melanoma is critical for improving outcomes. Here, we present the most comprehensive intrapatient metastatic melanoma dataset assembled to date as part of the Posthumous Evaluation of Advanced Cancer Environment (PEACE) research autopsy program, including 222 exome sequencing, 493 panel-sequenced, 161 RNA sequencing, and 22 single-cell whole-genome sequencing samples from 14 ICI-treated patients. We observed frequent whole-genome doubling and widespread loss of heterozygosity, often involving antigen-presentation machinery. We found KIT extrachromosomal DNA may have contributed to the lack of response to KIT inhibitors of a KIT-driven melanoma. At the lesion-level, MYC amplifications were enriched in ICI nonresponders. Single-cell sequencing revealed polyclonal seeding of metastases originating from clones with different ploidy in one patient. Finally, we observed that brain metastases that diverged early in molecular evolution emerge late in disease. Overall, our study illustrates the diverse evolutionary landscape of advanced melanoma.SIGNIFICANCE: Despite treatment advances, melanoma remains a deadly disease at stage IV. Through research autopsy and dense sampling of metastases combined with extensive multiomic profiling, our study elucidates the many mechanisms that melanomas use to evade treatment and the immune system, whether through mutations, widespread copy-number alterations, or extrachromosomal DNA.See related commentary by Shain, p. 1294. This article is highlighted in the In This Issue feature, p. 1275.</p

Late-Stage Metastatic Melanoma Emerges through a Diversity of Evolutionary Pathways

UNLABELLED: Understanding the evolutionary pathways to metastasis and resistance to immune-checkpoint inhibitors (ICI) in melanoma is critical for improving outcomes. Here, we present the most comprehensive intrapatient metastatic melanoma dataset assembled to date as part of the Posthumous Evaluation of Advanced Cancer Environment (PEACE) research autopsy program, including 222 exome sequencing, 493 panel-sequenced, 161 RNA sequencing, and 22 single-cell whole-genome sequencing samples from 14 ICI-treated patients. We observed frequent whole-genome doubling and widespread loss of heterozygosity, often involving antigen-presentation machinery. We found KIT extrachromosomal DNA may have contributed to the lack of response to KIT inhibitors of a KIT-driven melanoma. At the lesion-level, MYC amplifications were enriched in ICI nonresponders. Single-cell sequencing revealed polyclonal seeding of metastases originating from clones with different ploidy in one patient. Finally, we observed that brain metastases that diverged early in molecular evolution emerge late in disease. Overall, our study illustrates the diverse evolutionary landscape of advanced melanoma. SIGNIFICANCE: Despite treatment advances, melanoma remains a deadly disease at stage IV. Through research autopsy and dense sampling of metastases combined with extensive multiomic profiling, our study elucidates the many mechanisms that melanomas use to evade treatment and the immune system, whether through mutations, widespread copy-number alterations, or extrachromosomal DNA. See related commentary by Shain, p. 1294. This article is highlighted in the In This Issue feature, p. 1275