Engaging Stakeholders in Social Determinants of Health Quality Improvement Efforts.

Background Social determinants of health (SDOH) affect around 70% of health outcomes. However, it is not clear how to integrate SDOH into clinical practice and health care policy. This quality improvement project engaged stakeholders to identify SDOH factors relevant in an Alaska Native/American Indian health system and how to integrate SDOH data into electronic health records (EHRs). Methods The authors utilized an internal steering committee of clinical leadership; conducted focus groups with patients, practitioners, administrative staff, and clinical leaders; developed programmatic workgroups to engage with the health system; and coordinated with allied health systems. Results The Steering Committee members prioritized uses of SDOH data. Focus groups grounded work in local community values and refined SDOH subdomains. Workgroups developed data visualizations, such as EHR dashboards, to automate data collection for reporting and assess performance metrics. External stakeholders helped innovate ways to utilize SDOH data through community partnerships and advocacy work. Stakeholders liked how the holistic approach of SDOH looks at whole-person wellness and how it can improve patient-practitioner relationships and reduce health disparities. They were concerned about outdated SDOH data and how some sensitive SDOH could lead to unanticipated harms. Leaders emphasized developing an actionable, strengths-based SDOH framework. Conclusions Many initiatives call for integrating SDOH into health care and EHRs. Engaging diverse audiences helps guide the work. This engagement may be particularly helpful for minority-serving health systems. SDOH data collection can be stigmatizing for patients. Stakeholder engagement can mitigate that by identifying which SDOH data elements to prioritize, and how to utilize them.

Tribal Deliberations about Precision Medicine Research: Addressing Diversity and Inequity in Democratic Deliberation Design and Evaluation.

Deliberative democratic engagement is used around the globe to gather informed public input on contentious collective questions. Yet, rarely has it been used to convene individuals exclusively from Indigenous communities. The relative novelty of using this approach to engage tribal communities and concerns about diversity and inequities raise important methodological questions. We describe the design and quality outcomes for a 2.5-day deliberation that elicited views of American Indian and Alaska Native (AIAN) leaders about the potential value and ethical conduct of precision medicine research (PMR), an emerging approach to research that investigates the health effects of individual genetic variation in tandem with variation in health-relevant practices, social determinants, and environmental exposures. The event met key goals, such as relationship and rapport formation, cross-site learning, equality of opportunity to participate, and respect among participants in the context of disagreement.

Perspectives on Precision Medicine in a Tribally Managed Primary Care Setting.

BACKGROUND: Precision medicine (PM) research and clinical application is moving forward at a rapid pace. To ensure ethical inclusion of all populations in PM, in-depth understanding of diverse communities' views of PM research and PM implementation is necessary. METHODS: Semi-structured interviews were conducted to explore perspectives on PM in a tribally managed healthcare organization. Thematic analysis was used to analyze data from 46 interviews. RESULTS: Participants described gains in diagnostic efficiency, risk identification for preventable disease, and the advancement of population-specific biomedical research as key benefits of PM. Concerns expressed related to privacy risks associated with data-sharing, overpromising on PM, and managing patient expectations related to PM. Stakeholders encouraged PM implementation to be preceded by health education activities that leverage a range of communication strategies. CONCLUSION: Perspectives described in this study may aid in and should be considered prior to implementation of PM in this and other healthcare systems, especially those serving diverse populations.

Alaska Native genomic research: perspectives from Alaska Native leaders, federal staff, and biomedical researchers.

Meaningful engagement of Alaska Native (AN) tribes and tribal health organizations is essential in the conduct of socially responsible and ethical research. As genomics becomes increasingly important to advancements in medicine, there is a risk that populations not meaningfully included in genomic research will not benefit from the outcomes of that research. AN people have historically been underrepresented in biomedical research; AN underrepresentation in genomics research is compounded by mistrust based on past abuses, concerns about privacy and data ownership, and cultural considerations specific to this type of research. Working together, the National Human Genome Research Institute and two Alaska Native health organizations, Southcentral Foundation and the Alaska Native Health Board, cosponsored a workshop in July 2018 to engage key stakeholders in discussion, strengthen relationships, and facilitate partnership and consideration of participation of AN people in community-driven biomedical and genomic research. AN priorities related to translation of genomics research to health and health care, return of genomic results, design of research studies, and data sharing were discussed. This report summarizes the perspectives that emerged from the dialogue and offers considerations for effective and socially responsible genomic research partnerships with AN communities.

Power Sharing, Capacity Building, and Evolving Roles in ELSI: The Center for the Ethics of Indigenous Genomic Research.

Persistent, unresolved issues stemming from a legacy of scientific exploitation and bio-colonialism have kept many tribal nations from participating in genomic research. The Center for the Ethics of Indigenous Genomic Research (CEIGR) aims to model meaningful community engagement that moves toward more inclusive and equitable research practices related to genomics. This article reflects on key successes and challenges behind CEIGR's efforts to shape Ethical, Legal and Social Implications (ELSI) research in ways that are informed by Indigenous perspectives, to locate community partnerships at the center of genomics research, and to conduct normative and empirical research with Indigenous communities that is grounded in the concepts of reciprocity, transparency and cultural competency. The structure of CEIGR represents an important shift away from a traditional model centered on a university-based principal investigators toward a partner-centered research approach that emphasizes equity and community control by distributing power and decision-making across all CEIGR partner sites. We discuss three features of CEIGR that have contributed to this shift towards an equitable, community-driven partnership: 1) balancing local priorities with collective goals; 2) distributing power in ways that promote equitable partnerships; and 3) capacity building and co-learning across partner sites. The discussion of these three areas in this article speaks to a particular strength of our Center: the interdependence among partners and collective willingness to maintain a plasticity of leadership that creates space for all of our partners to lead, support, exchange and strengthen ELSI research.

Community Perspectives on Communicating About Precision Medicine in an Alaska Native Tribal Health Care System.

BACKGROUND: Precision medicine seeks to better tailor medical care to the needs of individual patients, but there are challenges involved in communicating to patients, health care providers, and health system leaders about this novel and complex approach to research and clinical care. These challenges may be exacerbated for Alaska Native and American Indian (ANAI) people, whose experiences of unethical research practices have left some ANAI communities hesitant to engage in research that involves extensive data-sharing and diminished control over the terms of data management and who may have distinct, culturally-informed communication needs and preferences. There is need for communication research to support Tribal health organizations and ANAI people as they consider implementation of and participation in precision medicine. To address that need, this study characterizes the informational needs and communication preferences of patients, providers, and leaders at an Alaska Native Tribal health organization. METHODS: We conducted 46 individual, semi-structured interviews to explore perspectives on precision medicine and related communication needs among patients, providers, and leaders of a Tribal health organization. Analysis involved team-based coding to identify a priori and emergent themes, followed by identification and recoding of content relevant to precision medicine informational needs and communication preferences. RESULTS: Patients, providers, and leaders were described as both sources and recipients of information about precision medicine. Information deemed essential for making decisions about whether to participate in or implement a precision medicine program included information about the clinical and research applications of precision medicine, benefits and risks, health system costs and impacts, and data management practices. Preferred communication channels included digital and non-digital informational materials, as well as in-person learning opportunities for individuals and groups. Participants also describe contextual factors and barriers that influenced the acceptability and effectiveness of approaches to health communication. CONCLUSION: Results can inform approaches to communicating information about precision medicine to stakeholders within Tribal and other health care systems considering implementation of precision medicine in clinical or research contexts.

Deliberative democracy and historical perspectives on American Indian/Alaska native political decision-making practices.

Public deliberation has risen to the forefront of governance as a technique for increasing participation in policy making. Scholars and practitioners have also noted the potential for deliberation to give greater influence to historically marginalized populations, such as Indigenous peoples. However, there has been less attention paid to the potential fit between the ideals of deliberation and the governance and decision making practices of American Indian and Alaska Native (AI/AN) peoples. In this paper, we begin to address this gap by analyzing accounts of AI/AN governance from the perspective of deliberation, and note areas of overlap, synergy, and conflict. We conduct a close reading of key historical and ethnographic accounts of four historical AI/AN contexts-the Iroquois Confederation under the Great Law of Peace, 19th century accounts of the Ojibwa village, the Santa Clara Pueblo government in pre-19th century, and Yup'ik village life in the early 20th century-and a more contemporary case in the form of the Santa Clara Pueblo's Constitution from the Indian Reorganization Act period. We then apply two sets of key criteria for deliberative democracy-from the scholars Robert Dahl and John Gastil-to these accounts and note the ways in which each system is or is not congruent with these frameworks of deliberation. We find variations between these historical tribal contexts in our analysis. Social components of deliberation, such as respectful discussion and equal opportunities to participate, were partially or fully present in many accounts of governance practices, but it was less clear whether the analytic components, such as discussion of a range of solutions, were included in some forms of tribal governance. We then explore the potential implications of our findings for public deliberation within and in AI/AN tribes. We note that deliberative scholars and practitioners should be wary of over-generalizing about AI/AN tribes.

Fostering Ethical, Legal, and Social Implications Research in Tribal Communities: The Center for the Ethics of Indigenous Genomic Research.

Genomic research raises unique ethical concerns among Alaska Native and American Indian (AN/AI) people and their communities. The Center for the Ethics of Indigenous Genomic Research (CEIGR) was created to foster research that takes these concerns into account while considering the sovereign status of AN/AI tribal nations. Relationships developed within CEIGR have allowed for effective, collaborative research among individuals who come from diverse cultures, political and historical backgrounds, and academic disciplines, and who work for organizations with varying resources, capacities, and expectations. The CEIGR framework may inform other groups seeking to conduct social science research related to genomic research with tribal people and their communities.

Data Management in Health-Related Research Involving Indigenous Communities in the United States and Canada: A Scoping Review.

Background: Multiple factors, including experiences with unethical research practices, have made some Indigenous groups in the United States and Canada reticent to participate in potentially beneficial health-related research. Yet, Indigenous peoples have also expressed a willingness to participate in research when certain conditions related to the components of data management-including data collection, analysis, security and storage, sharing, dissemination, and withdrawal-are met. A scoping review was conducted to better understand the terms of data management employed in health-related research involving Indigenous communities in the United States and Canada. Methods: PubMed, Embase, PsychINFO, and Web of Science were searched using terms related to the populations and topics of interest. Results were screened and articles deemed eligible for inclusion were extracted for content on data management, community engagement, and community-level research governance. Results: The search strategy returned 734 articles. 31 total articles were extracted, of which nine contained in-depth information on data management and underwent detailed extraction. All nine articles reported the development and implementation of data management tools, including research ethics codes, data-sharing agreements, and biobank access policies. These articles reported that communities were involved in activities and decisions related to data collection (n=7), data analysis (n=5), data-sharing (n=9), dissemination (n=7), withdrawal (n=4), and development of data management tools (n=9). The articles also reported that communities had full or shared ownership of (n=5), control over (n=9), access to (n=1), and possession of data (n=5). All nine articles discussed the role of community engagement in research and community-level research governance as means for aligning the terms of data management with the values, needs, and interests of communities. Conclusions: There is need for more research and improved reporting on data management in health-related research involving Indigenous peoples in the United States and Canada. Findings from this review can provide guidance for the identification of data management terms and practices that may be acceptable to Indigenous communities considering participation in health-related research.

Community Protections in American Indian and Alaska Native Participatory Research-A Scoping Review.

Experiences with unethical research practices have caused some American Indian and Alaska Native (AIAN) individuals, organizations, and tribes to mistrust health research. To build trust and repair relationships, current research with AIAN peoples often involves participatory research (PR) approaches. This article assesses community-level protections described in the scientific literature on PR involving AIAN communities. A scoping review search in PubMed and PsychInfo for articles published between January 2000 and June 2017 yielded an AIAN PR article dataset. Of 178 articles, a subset of 23 articles that described aspects of community protections were analyzed for descriptions of community-level protection practices. We identified the presence or absence of a description of four community protection measures in each article: a tribal research department, the development of community-level mechanisms for research regulation if not present, community collaboration throughout the research process, and project employment of a community member. The development of community-level mechanisms for research regulation was described in 39% of the articles. Ninety-one percent of these articles described community collaboration during the research process. Seventeen percent included descriptions of all four community-level protection measures. The extent and consistency to which community-level protections are described is variable; the current literature lacks reporting on community-level protection practices specific to tribal communities.

Health-Related Participatory Research in American Indian and Alaska Native Communities: A Scoping Review.

A scoping review was conducted to assess the state of the literature on health-related participatory research involving American Indian and Alaska Native communities. Online databases were searched for relevant articles published between 1/1/2000 and 5/31/2017. 10,000+ data points relevant to community-level engagement in and regulation of research, community research capacity and cultural adaptation were extracted from 178 articles. Community engagement varied across study components: 136 (76%) articles reported community participation in research-related meetings and other events and 49 (27%) articles reported community involvement in initiation of research. 156 (88%) articles reported use of community-level tools to guide or regulate research. 93 (52%) articles reported that community members received research-related training. 147 (82%) articles described some type of cultural adaptation. Across all articles, data points on community engagement were not reported in 3061 (40%) out of 7740 cases. Findings suggest a need for increased community engagement in early stages of the research process and for reporting guidelines for participatory research involving American Indian and Alaska Native communities. There is also need to further existing research on the impact of different components of participatory research on process and outcome measures and to develop funding mechanisms that account for the time and resource intensive nature of participatory research.

Mass discharge assessment at a brominated DNAPL site: Effects of known DNAPL source mass removal.

Management and closure of contaminated sites is increasingly being proposed on the basis of mass flux of dissolved contaminants in groundwater. Better understanding of the links between source mass removal and contaminant mass fluxes in groundwater would allow greater acceptance of this metric in dealing with contaminated sites. Our objectives here were to show how measurements of the distribution of contaminant mass flux and the overall mass discharge emanating from the source under undisturbed groundwater conditions could be related to the processes and extent of source mass depletion. In addition, these estimates of mass discharge were sought in the application of agreed remediation targets set in terms of pumped groundwater quality from offsite wells. Results are reported from field studies conducted over a 5-year period at a brominated DNAPL (tetrabromoethane, TBA; and tribromoethene, TriBE) site located in suburban Perth, Western Australia. Groundwater fluxes (qw; L(3)/L(2)/T) and mass fluxes (Jc; M/L(2)/T) of dissolved brominated compounds were simultaneously estimated by deploying Passive Flux Meters (PFMs) in wells in a heterogeneous layered aquifer. PFMs were deployed in control plane (CP) wells immediately down-gradient of the source zone, before (2006) and after (2011) 69-85% of the source mass was removed, mainly by groundwater pumping from the source zone. The high-resolution (26-cm depth interval) measures of qw and Jc along the source CP allowed investigation of the DNAPL source-zone architecture and impacts of source mass removal. Comparable estimates of total mass discharge (MD; M/T) across the source zone CP reduced from 104gday(-1) to 24-31gday(-1) (70-77% reductions). Importantly, this mass discharge reduction was consistent with the estimated proportion of source mass remaining at the site (15-31%). That is, a linear relationship between mass discharge and source mass is suggested. The spatial detail of groundwater and mass flux distributions also provided further evidence of the source zone architecture and DNAPL mass depletion processes. This was especially apparent in different mass-depletion rates from distinct parts of the CP. High mass fluxes and groundwater fluxes located near the base of the aquifer dominated in terms of the dissolved mass flux in the profile, although not in terms of concentrations. Reductions observed in Jc and MD were used to better target future remedial efforts. Integration of the observations from the PFM deployments and the source mass depletion provided a basis for establishing flux-based management criteria for the site.

The use of mass depletion-mass flux reduction relationships during pumping to determine source zone mass of a reactive brominated-solvent DNAPL.

Mass depletion-mass flux relationships usually applied to a groundwater plume were established at field scale for groundwater pumped from within the source zone of a dense non-aqueous phase liquid (DNAPL). These were used as part of multiple lines of evidence in establishing the DNAPL source mass and architecture. Simplified source mass-dissolved concentration models including those described by exponential, power, and error functions as well as a rational mass equation based on the equilibrium stream tube approach were fitted to data from 285 days of source zone pumping (SZP) from a single well which removed 152 kg of dissolved organics from a multi-component, reactive brominated solvent DNAPL. The total molar concentration of the source compound, tetrabromoethane and its daughter products was used as a single measure of contaminant concentration to relate to source mass. A partitioning inter-well tracer test (PITT) conducted prior to the SZP provided estimates of groundwater travel times, enabling parameterisation of the models. After accounting for capture of the down-gradient dissolved plume, all models provided a good fit to the observed data. It was shown that differentiation between models would only emerge after appreciably more pumping from the source zone. The model fits were not particularly sensitive to the exponent parameters and variance of groundwater travel time. In addition, the multi-component nature of the DNAPL did not seem to affect the utility of the models for the period examined. Estimates of the DNAPL mass prior to the start of SZP from the models were greatest where the log of the variance of travel time was used explicitly in the source depletion models (mean 295kg) compared to where the associated power exponent and variance was fitted freely (mean 258 kg). The estimates of source mass were close to that of 220kg determined from the PITT. In addition to the PITT, multi-level groundwater sampling from within the source zone provided important supporting information for developing the conceptual model of the source zone. It is concluded that SZP may be an effective and relatively simple means for characterising DNAPL source zones.

Proteomic profiling of the rat cerebral cortex in sleep and waking.

Transcriptomic studies have shown that hundreds of genes change their expression levels across the sleep/waking cycle, and found that waking-related and sleep-related mRNAs belong to different functional categories. Proteins, however, rather than DNA or RNA, carry out most of the cellular functions, and direct measurements of protein levels and activity are required to assess the effects of behavioral states on the overall functional state of the cell. Here we used surface-enhanced laser desorption-ionization (SELDI), followed by time-of-flight mass spectrometry, to obtain a large-scale profiling of the proteins in the rat cerebral cortex whose expression is affected by sleep, spontaneous waking, short (6 hours) and long (7 days) sleep deprivation. Each of the 94 cortical samples was profiled in duplicate on 4 different ProteinChip Array surfaces using 2 different matrix molecules. Overall, 1055 protein peaks were consistently detected in cortical samples and 15 candidate biomarkers were selected for identification based on significant changes in multiple conditions (conjunction analysis): 8 "sleep" peaks, 4 "waking" peaks, and 4 "long sleep deprivation" peaks. Four candidate biomarkers were purified and positively identified. The 3353 Da candidate sleep marker was identified as the 30 amino acid C-terminal fragment of rat histone H4. This region encompasses the osteogenic growth peptide, but a possible link between sleep and this peptide remains highly speculative. Two peaks associated with short and long sleep deprivation were identified as hemoglobin alpha1/2 and beta, respectively, while another peak associated with long sleep deprivation was identified as cytochrome C. The upregulation of hemoglobins and cytochrome C may be part of a cellular stress response triggered by even short periods of sleep loss.

Direct demonstration that homotetrameric chaperone SecB undergoes a dynamic dimer-tetramer equilibrium.

We have shown here that the cytosolic bacterial chaperone SecB is a structural dimer of dimers that undergoes a dynamic equilibrium between dimer and tetramer in the native state. We demonstrated this equilibrium by mixing two tetrameric species of SecB that can be distinguished by size. We showed that the homotetrameric species exchanged dimers, because when the mixture was analyzed both by size exclusion chromatography and native polyacrylamide gel electrophoresis a third hybrid tetrameric species was detected. Furthermore, treatment of SecB with 5,5'-dithiobis-(2-nitrobenzoic acid), which modifies the sulfhydryl group on cysteines, caused irreversible dissociation to a dimer indicating that cysteine must be involved in the stabilizing interactions at the dimer interface. It is clear that the two dimer-dimer interfaces of the SecB tetramer are differentially stable. Dissociation at one interface allows for a dynamic dimer-tetramer equilibrium. Because only dimers were exchanged it is clear that the other interface between dimers is significantly more stable, otherwise oligomers should have formed with a random distribution of monomers.

Complexes between protein export chaperone SecB and SecA. Evidence for separate sites on SecA providing binding energy and regulatory interactions.

During localization to the periplasmic space or to the outer membrane of Escherichia coli some proteins are dependent on binding to the cytosolic chaperone SecB, which in turn is targeted to the membrane by specific interaction with SecA, a peripheral component of the translocase. Five variant forms of SecB, previously demonstrated to be defective in mediating export in vivo (Gannon, P. M., and Kumamoto, C. A. (1993) J. Biol. Chem. 268, 1590-1595; Kimsey, H. K., Dagarag, M. D., and Kumamoto, C. A. (1995) J. Biol. Chem. 270, 22831-22835) were investigated with respect to their ability to bind SecA both in solution and at the membrane translocase. We present evidence that at least two regions of SecA are involved in the formation of active complexes with SecB. The variant forms of SecB were all capable of interacting with SecA in solution to form complexes with stability similar to that of complexes between SecA and wild-type SecB. However, the variant forms were defective in interaction with a separate region of SecA, which was shown to trigger a change that was correlated to activation of the complex. The region of SecA involved in activation of the complexes was defined as the extreme carboxyl-terminal 21 aminoacyl residues.

Early retirement in the United States.

Despite improvements in health and longevity, many workers in the United States retire young. By age 62, only 44 percent of men and 24 percent of women are still working full-time. The combination of younger retirement and increasing longevity means that Americans are spending more years in retirement than at any time in history. The widespread availability of post-retirement benefits is an important aspect of this national trend. Eligibility for employer-provided retirement benefits can begin as young as age 50 and occurs quite frequently at age 55. Eligibility for Social Security benefits begins at age 62. Eligibility for Medicare begins at age 65. As the population ages, the implementation of cost-saving reforms in retirement programs has become an increasing policy concern. To sustain the major public entitlement programs, proposals have been made to raise the age of eligibility for Social Security and Medicare, or to reduce benefit levels, or to target benefits to those most in need. Other cost-saving changes have been considered, and in many cases implemented, in employer-provided retirement benefits. These policy changes will have implications for the retirement decisions of working Americans in the future. This report, drawing on research sponsored by the National Institute on Aging, reviews the trend in the United States toward earlier retirement as well as some recent research findings on how retirement decisions relate to public and private retirement policies. With the changing age demographics of the population, the implementation of cost-saving reforms to retirement policies and other changes in the economic circumstances of individuals as they age, the work and retirement decisions of older workers will continue to evolve over the coming decades.

Construction of biosensors using a gold-binding polypeptide and a miniature integrated surface plasmon resonance sensor.

Surface plasmon resonance (SPR) biosensors were constructed on miniature integrated sensors. Recognition elements were attached to the sensor surface using a gold-binding repeating polypeptide. Biosensors with fluorescyl groups attached to their surfaces were functional for at least 1 month of daily use with little decrease in response to the binding of an anti-fluorescyl monoclonal antibody. The coupling of protein A to the gold-binding polypeptide on the sensor surface enabled the biosensor to detect the binding of antibodies to the protein A and provided a sensor with convertible specificity. The system described herein provides a simple and rapid approach for the fabrication of highly specific, durable, portable and low cost SPR-based biosensors.

Aspartic acid 413 is important for the normal allosteric functioning of ADP-glucose pyrophosphorylase.

As part of a structure-function analysis of the higher-plant ADP-glucose pyrophosphorylase (AGP), we used a random mutagenesis approach in combination with a novel bacterial complementation system to isolate over 100 mutants that were defective in glycogen production (T.W. Greene, S.E. Chantler, M.L. Khan, G.F. Barry, J. Preiss, T.W. Okita [1996] Proc Natl Acad Sci USA 93: 1509-1513). One mutant of the large subunit M27 was identified by its capacity to only partially complement a mutation in the structural gene for the bacterial AGP (glg C), as determined by its light-staining phenotype when cells were exposed to l3 vapors. Enzyme-linked immunosorbent assay and enzymatic pyrophosphorylysis assays of M27 cell extracts showed that the level of expression and AGP activity was comparable to those of cells that expressed the wild-type recombinant enzyme. Kinetic analysis indicated that the M27 AGP displays normal Michaelis constant values for the substrates glucose-1-phosphate and ATP but requires 6- to 10-fold greater levels of 3-phosphoglycerate (3-PGA) than the wild-type recombinant enzyme for maximum activation. DNA sequence analysis showed that M27 contains a single point mutation that resulted in the replacement of aspartic acid 413 to alanine. Substitution of a lysine residue at this site almost completely abolished activation by 3-PGA. Aspartic acid 413 is adjacent to a lysine residue that was previously identified by chemical modification studies to be important in the binding of 3-PGA (K. Ball, J. Preiss [1994] J Biol Chem 269: 24706-24711). The kinetic properties of M27 corroborate the importance of this region in the allosteric regulation of a higher-plant AGP.