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Health equity is the state in which everyone has fair and just opportunities to attain their highest level of health. The field of human genomics has fallen short in increasing health equity, largely because the diversity of the human population has been inadequately reflected among participants of genomics research. This lack of diversity leads to disparities that can have scientific and clinical consequences. Achieving health equity related to genomics will require greater effort in addressing inequities within the field. As part of the commitment of the National Human Genome Research Institute (NHGRI) to advancing health equity, it convened experts in genomics and health equity research to make recommendations and performed a review of current literature to identify the landscape of gaps and opportunities at the interface between human genomics and health equity research. This Perspective describes these findings and examines health equity within the context of human genomics and genomic medicine., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background: Food insecurity is an important social determinant of health that was exacerbated by the COVID-19 pandemic. Both food insecurity and COVID-19 infection disproportionately affect racial and ethnic minority groups, particularly American Indian and Alaska Native communities; however, there is little evidence as to whether food insecurity is associated with COVID-19 infection or COVID-19 preventive behaviors such as vaccination uptake. The purpose of this study was to evaluate associations between food insecurity, COVID-19 infection, and vaccination status among urban American Indian and Alaska Native adults seen at 5 clinics serving urban Native people., Methods: In partnership with health organizations in Alaska, Colorado, Kansas, Minnesota, and New Mexico, the study team conducted a cross-sectional survey in 2021 to assess food security status and attitudes, barriers, and facilitators for COVID-19 testing and vaccination. Logistic regression was used to examine the association of food security status with sociodemographic factors and COVID-19 infection and vaccination status. Marginal standardization was applied to present results as prevalence differences., Results: Among 730 American Indian and Alaska Native adults, the prevalence of food insecurity measured during the pandemic was 38%. For participants who reported persistent food security status before and during the pandemic (n = 588), the prevalence of food insecurity was 25%. Prevalence of COVID-19 infection and vaccination did not vary by food security status after adjustment for confounders., Conclusions: High rates of food insecurity among American Indian and Alaska Native communities likely increased during the COVID-19 pandemic. However, despite the high prevalence of food insecurity, community-led efforts to reduce COVID-19 infection and increase vaccination uptake across Indian Health Service and Tribal healthcare facilities may have mitigated the negative impacts of the pandemic for families experiencing food insecurity. These successful approaches serve as an important reference for future public health efforts that require innovative strategies to improve overall health in American Indian and Alaska Native communities., (© 2024. The Author(s).)

Introduction: Alaska Native and American Indian (ANAI) people have a smoking prevalence of 23%. Nicotine metabolite ratio (NMR) and genetic testing may enable tailored selection of tobacco cessation medication., Aims and Methods: The purpose of this study was to evaluate the relative contributions of NMR, cessation medication, demographics, and tobacco use history to cessation. Participants were recruited into an observational cohort study consisting of a baseline visit prior to their quit date and 6-week follow-up. Demographic and tobacco use surveys and blood, urine, and breath samples were collected at each visit. Electronic health records were queried for cessation medications. NMR was categorized into slow or normal nicotine metabolism phenotypes (<0.31 and ≥ 0.31, respectively). The main outcome was cessation at 6 weeks. Analyses consisted of descriptive statistics, medication and phenotype concordance, and estimates of relative risk (RR) of quitting., Results: We enrolled 151 ANAI adults who smoked cigarettes daily. Two-thirds had normal nicotine metabolism phenotype. Retrospective medication and phenotype concordance was 39%. The overall quit rate was 25%. No demographic factors or tobacco use history were associated with quit success. Varenicline and bupropion increased the likelihood of quitting (RR = 2.93 [1.42, 6.03] and RR = 2.52 [1.12, 5.64], respectively) compared to nicotine replacement therapy. Non-optimal medication and phenotype concordance decreased likelihood of quit success (RR = 0.44 [0.22, 0.91]) compared to optimal concordance., Conclusions: This exploratory study found associations between quit success and tobacco cessation medication as well as medication and phenotype concordance. Additional research is needed to assess use of NMR for treatment selection among ANAI people., Implications: These results broadly support additional community-engaged research to improve medication and phenotype concordance in tribal health settings. Such future research on implementing meditcation and phenotype concordance holds promise to improve expectations, quit success, and health outcomes amongst individuals attempting to quit smoking., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: Health care organizations of all types have adapted in response to COVID-19. Responding to the pandemic has varied across organizations and there are few standardized frameworks from which to evaluate an organizational response. This article reports COVID-19 responses by a tribal health care organization using a synthesized evaluation framework that integrated the organizational values and allowed for timely implementation of responses during this COVID-19 public health emergency., Methods: The authors categorized each COVID-19 response into six domains, including leadership practices, patient engagement, operations management, teamwork and communication, public health, and external partnerships. Responses were analyzed by domain and across time., Results: COVID-19 responses included medical alerts, modifying delivery of care, establishing testing and vaccination sites, additional benefits for employees, as well as new processes for communication between employees and senior leadership. COVID-19 responses were most frequently categorized into the operation management domain (80%). Many responses, especially those that considered patients, employees, and the community, also fit other domains., Discussion: Operation management was the most frequent domain because the pandemic emerged rapidly and required swift, agile, action-oriented responses from the tribal health care organization. The majority of COVID-19 responses involved multiple, not single, domains., Conclusion: Our evaluation approach captured areas of importance to the tribal health organization and may be pertinent for other indigenous organizations and rural communities. It is especially important to consider tribal perspectives in response to COVID-19 because of the prior history with Western medicine and infectious diseases, and health care limitations experienced due to rurality., Competing Interests: Conflicts of Interest None declared

Newborn screening in Alaska includes screening for carnitine palmitoyltransferase 1A (CPT1A) deficiency. The CPT1A Arctic variant is a variant highly prevalent among Indigenous peoples in the Arctic. In this study, we sought to elicit Alaska Native (AN) community member and AN-serving healthcare providers' knowledge and perspectives on the CPT1A Arctic variant. Focus groups with community members and healthcare providers were held in two regions of Alaska between October 2018 and January 2019. Thematic analysis was used to identify recurring constructs. Knowledge and understanding about the CPT1A Arctic variant and its health impact varied, and participants were interested in learning more about it. Additional education for healthcare professionals was recommended to improve providers' ability to communicate with family caregivers about the Arctic variant. Engagement with AN community members identified opportunities to improve educational outreach via multiple modalities for providers and caregivers on the Arctic variant, which could help to increase culturally relevant guidance and avoid stigmatization, undue worry, and unnecessary intervention. Education and guidance on the care of infants and children homozygous for the CPT1A Arctic variant could improve care and reduce negative psychosocial effects., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Little is known about vaccination rates for American Indian and Alaska Native (AI/AN) parents and their children, or parental decisions in this regard. Improving vaccination rates is a serious concern due to the disproportionate incidence and morbidity of COVID-19 in AI/AN people., Purpose: Our goal was to describe urban AI/AN parental attributes associated with COVID-19 vaccination of their children., Methods: Survey participants (n = 572) were ≥18 years of age, had children ≥5 years of age, AI/AN, and seen at one of six urban health organizations serving primarily AI/AN people within the prior year. They were asked about gender, age, education, marital status, perceived stress, trauma history, whether they had received the COVID-19 vaccine, tested positive for COVID-19 in the past, and if their child was vaccinated. They were also asked about 16 vaccine hesitancy reasons., Results: Parental vaccination rate was 82%, with 59% of their children vaccinated. Parents who vaccinated their children were older, had higher education, lower stress and trauma, and were more likely to be vaccinated compared to parents who did not vaccinate their children. Forty-two percent of parents indicated they would likely vaccinate their unvaccinated child in the future. Sixteen vaccine hesitancy reasons revealed four factors: distrust, inconvenience, lack of concern about the pandemic, and AI/AN concerns. Parents who had no plans to vaccinate their children had the highest vaccine distrust and lack of concern about the pandemic. Parents with greater vaccine distrust and AI/AN specific concern reported significantly greater trauma history and higher levels of education., Conclusion: Even though vaccination rates for AI/AN parents and children are high, the consequences of COVID-19 for AI/AN people are more severe than for other US populations. Providers should use trauma-informed, trust-building and culturally competent communication when discussing choices about vaccination with AI/AN parents., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Research reported in this publication was supported by the National Institute Of Minority Health And Health Disparities of the National Institutes of Health under Award Number U54MD011240 and the National Institute Of Allergy And Infectious Disease of the National Institutes of Health under Award Number R01AI170946. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health., (© 2023 The Authors.)

The vagina undergoes large finite deformations and has complex geometry and microstructure, resulting in material and geometric nonlinearities, complicated boundary conditions, and nonhomogeneities within finite element (FE) simulations. These nonlinearities pose a significant challenge for numerical solvers, increasing the computational time by several orders of magnitude. Simplifying assumptions can reduce the computational time significantly, but this usually comes at the expense of simulation accuracy. This study proposed the use of reduced order modeling (ROM) techniques to capture experimentally measured displacement fields of rat vaginal tissue during inflation testing in order to attain both the accuracy of higher-fidelity models and the speed of simpler simulations. The proper orthogonal decomposition (POD) method was used to extract the significant information from FE simulations generated by varying the luminal pressure and the parameters that introduce the anisotropy in the selected constitutive model. A new data-driven (DD) variational multiscale (VMS) ROM framework was extended to obtain the displacement fields of rat vaginal tissue under pressure. For comparison purposes, we also investigated the classical Galerkin ROM (G-ROM). In our numerical study, both the G-ROM and the DD-VMS-ROM decreased the FE computational cost by orders of magnitude without a significant decrease in numerical accuracy. Furthermore, the DD-VMS-ROM improved the G-ROM accuracy at a modest computational overhead. Our numerical investigation showed that ROM has the potential to provide efficient and accurate computational tools to describe vaginal deformations, with the ultimate goal of improving maternal health., (© 2022 John Wiley & Sons Ltd.)

Objectives: Attitudes about alcohol misuse and dependence influence alcohol use and help-seeking behavior. Alaska Native and American Indian (AN/AI) people have higher rates of alcohol-related morbidity and mortality but engage in treatment at lower rates than the general population. No validated instruments exist to assess attitudes of AN/AI people about alcohol misuse and dependence to inform treatment and prevention efforts. This study aimed to develop an instrument to assess public attitudes among AN/AI people of alcohol misuse and dependence., Methods: This multiphase, mixed-methods study was conducted at Southcentral Foundation, a tribally owned health system serving 65,000 AN/AI people in Alaska. We conducted focus groups and interviews with health system users, providers, and leaders to adapt the Public Attitudes About Addiction Survey. The adapted instrument was piloted with 200 people. Cognitive interviews and exploratory and confirmatory factor analyses were used to refine the instrument, which were then administered to 777 AN/AI people., Results: Initial exploratory factor analysis identified 5 factors, including 3 from the original Public Attitudes About Addiction Survey (moral, disease, nature), a combined psychology and sociology factor (psychosocial), and a new factor (environment). A final 4-factor model (psychosocial, moral, disease, nature) with 14 items had good fit with root mean square error of approximation (0.035; comparative fit index = 0.977; Tucker-Lewis index = 0.970; standardized root mean residual = 0.040) and loadings ranging from 0.41 to 0.80., Conclusions: This study developed the first instrument to assess AN/AI attitudes about alcohol misuse and dependence. This instrument has potential to inform alcohol-related treatment in AN/AI communities. Future research is warranted to adequately measure place-based contributors salient to AN/AI people., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 American Society of Addiction Medicine.)

Objectives: To examine the relationships between pre-pregnancy diabetes mellitus (DM), gestational diabetes mellitus (GDM), pre-pregnancy body mass index (BMI) and county-level social determinants of health, with infant macrosomia within a sample of American Indian/Alaska Native (AI/AN) women receiving Indian Health Service (IHS) care., Methods: The sample included women-infant dyads representing 1,136 singleton births from fiscal year 2011 (10/1/2019-9/30/2011). Data stemmed from the IHS Improving Health Care Delivery Data Project. Multivariate generalized linear mixed models were fitted to assess the association of macrosomia with pre-pregnancy health status and social determinants of health., Results: Nearly half of the women in the sample were under age 25 years (48.6%), and most had Medicaid health insurance coverage (76.7%). Of those with a pre-pregnancy BMI measure, 66.2% were overweight or obese. Although few women had pre-pregnancy DM (4.0%), GDM was present in 12.8% of women. Most women had a normal term delivery (85.4%). Overweight, obesity, pre-pregnancy DM, and county-level rurality were all significantly associated with higher odds of infant macrosomia., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The prevalence of self-reported hypertension is higher among Alaska Native and American Indian (ANAI) individuals than in the majority USA population. Although hypertension is the primary modifiable risk factor for cardiovascular disease and stroke, it can be difficult to manage successfully. The objective of this study was to explore patients' and providers' perspectives about hypertension, hypertension management strategies, and patient-provider communication strategies within a tribally-owned and operated health system in Alaska. We conducted four focus groups that included 16 ANAI patients and five primary care providers. Patient participants tended to consider hypertension a transient state, in contrast with providers' understanding of hypertension as a chronic condition. Differences were noted in participants' perceptions regarding providers' counselling and education efforts, with providers feeling that current strategies are effective and patients desiring a more personalised discussion about hypertension. Patients expressed preferences for behaviour change approaches compared with pharmacotherapy; providers often resorted to medication as a first step towards controlling blood pressure. Our findings suggest areas of potentially promising future research with respect to patient-provider communication and treatment of hypertension.

The vagina is a highly inhomogeneous, anisotropic, and viscoelastic organ that undergoes significant deformations in vivo. The mechanical attributes of this organ facilitate important physiological functions during menstruation, intercourse, and birthing. Despite the crucial mechanical role that the vagina plays within the female reproductive system, the deformations that the organ can sustain over time under constant pressure, in both the longitudinal direction (LD) and circumferential direction (CD), have not been fully characterized. This experimental study focuses on quantifying the creep properties of the vagina via ex vivo inflation testing using the rat as animal model. Toward this end, rat vaginas were subjected to three consecutively increasing constant luminal pressures (28 kPa, 55 kPa, and 83 kPa) using a custom-built experimental setup and the resulting inhomogeneous deformations were measured using the digital image correlation (DIC) method. The vagina was found to deform significantly more in the CD than the LD at any constant pressure, suggesting that the organ primarily adapts to constant pressures by significantly changing the diameter rather that the length. The change in deformation over time (i.e., creep) was significantly higher during the 1st inflation test at a constant pressure of 28 kPa than over the 2nd and 3rd inflation tests at constant pressures of 55 kPa and 83 kPa, respectively. The findings of this study on the mechanical behavior of the vagina could serve to advance our limited knowledge about the physiology and pathophysiology of this important reproductive organ., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology.)

Background: Home blood pressure monitoring (HBPM) is an effective tool in treatment and long-term management of hypertension. HBPM incorporates more data points to help patients and providers with diagnosis and management. The characteristics of HBPM devices matter to patients, but the relative importance of the characteristics in choosing a device remains unclear., Methods: We used data from a randomized cross-over pilot study with 100 Alaska Native and American Indian (ANAI) people with hypertension to assess the choice of a wrist or arm HBPM device. We use a random utility framework to evaluate the relationship between stated likely use, perceived accuracy, ease of use, comfort, and participant characteristics with choice of device. Additional analyses examined willingness to change to a more accurate device., Results: Participants ranked the wrist device higher compared to the arm on a 5-point Likert scale for likely use, ease of use, and comfort (0.3, 0.5, 0.8 percentage points, respectively). Most participants (66%) choose the wrist device. Likely use (wrist and arm devices) was related to the probability of choosing the wrist (0.7 and - 1.4 percentage points, respectively). Independent of characteristics, 75% of participants would be willing to use the more accurate device. Ease of use (wrist device) and comfort (arm device) were associated with the probability of changing to a more accurate device (- 1.1 and 0.5 percentage points, respectively)., Conclusion: Usability, including comfort, ease, and likely use, appeared to discount the relative importance of perceived accuracy in the device choice. Our results contribute evidence that ANAI populations value accurate HBPM, but that the devices should also be easy to use and comfortable to facilitate long-term management., (© 2022. The Author(s).)

Capitalizing on features including high resolution, smooth surface finish, large build volume, and simultaneous multi-color/multi-material printing, material jetting additive manufacturing enables the fabrication of full-scale anatomic models. The ability to print materials that resemble relevant, compliant tissues has especially motivated implementation of material jetting for patient-specific surgical planning or training models. In an effort to broaden the material selection for the material jetting process, and to provide materials that more closely mimic the functional needs for a wider variety of tissues, a composite material system is explored that uses non-curing fluid dispersed into a photo-curable medium. The material properties of the composites are examined through both thermal and mechanical analysis (dynamic mechanical analysis, Shore hardness testing, puncture testing, and tensile testing). Higher contributions of non-curing fluid generally reduce part strength and stiffness, and exponential and second-order polynomial expressions are appropriate fits for many of the mechanical properties as functions of non-curing fluid concentration. Through the fundamental exploration of the impact of an added diluent on material properties, the study advances knowledge on the process-property relationship for multi-material jetting. Additionally, better understanding of the mechanical property space offered by these materials will expand the capabilities of material jetting in the context of biomedical applications. The collection of mechanical properties serve as reference data sets to facilitate quicker screening for tissue-mimicking, medical models., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Participant retention in longitudinal health research is necessary for generalizable results. Understanding factors that correlate with increased retention could improve retention in future studies. Here, we describe how participant and study process measures are associated with retention in a longitudinal tobacco cessation research study performed in Anchorage, Alaska. Specifically, we conducted a secondary analysis exploring retention among 151 Alaska Native and American Indian (ANAI) people and described our study processes using study retention categories from a recent meta-analysis. We found that our study processes influence retention among ANAI urban residents more than measures collected about the participant. For study process measures, calls where a participant answered and calls participants placed to the study team were associated with higher retention. Calls where the participant did not answer were associated with lower retention. For participant measures, only lower annual income was associated with lower retention at 6 weeks. Promoting communication from participants to the study team could improve retention, and alternative communication methods could be used after unsuccessful calls. Finally, categorizing our study retention strategies demonstrated that additional barrier-reduction strategies might be warranted.

Prevalence of smoking is higher in Alaska Native and American Indian (ANAI) populations living in Alaska than the general US population. Genetic factors contribute to smoking and cessation rates. The objective of this study was to compare CYP2A6 genetic variation and CYP2A6 enzyme activity toward nicotine in an ANAI population. ANAI (N = 151) people trying to quit smoking were recruited. DNA samples were genotyped for CYP2A6 variants *1X2A, *1B, *2, *4, *9, *10, *12, and *35. Multiple nicotine metabolites were measured in plasma and urine samples, including cotinine and 3'-hydroxycotinine used to determine CYP2A6 activity (e.g., nicotine metabolite ratio [NMR]). We calculated summary statistics for all of the genotypes and metabolites and assigned CYP2A6 activity scores based on known information. We studied the association of CYP2A6 variants with the NMR and smoking histories. The overall frequency of the CYP2A6*1B gain of function allele was high in the ANAI versus non-ANAI populations in other studies. Both *4 null and *9 decrease of function alleles had frequencies similar to previous studies of ANAI populations. In a multivariate analysis, the genotype-inferred CYP2A6 activity score was associated with both plasma and urine NMR (p value = 8.56E-08 and 4.08E-13, respectively). Plasma NMR was also associated with duration of smoking (p value < 0.01) but not urinary total nicotine equivalents uncorrected for creatinine (TNE9 uc ) or biological sex. Urine NMR was significantly associated (p value < 0.01) with TNE9 uc . Variation in NMR in this ANAI population is explained in part by CYP2A6 genetic variation., (© 2021 The Authors. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

We provide guidance for conducting clinical trials with Indigenous children in the United States. We drew on extant literature and our experience to describe 3 best practices for the ethical and effective conduct of clinical trials with Indigenous children. Case examples of pediatric research conducted with American Indian, Alaska Native, and Native Hawaiian communities are provided to illustrate these practices. Ethical and effective clinical trials with Indigenous children require early and sustained community engagement, building capacity for Indigenous research, and supporting community oversight and ownership of research. Effective engagement requires equity, trust, shared interests, and mutual benefit among partners over time. Capacity building should prioritize developing Indigenous researchers. Supporting community oversight and ownership of research means that investigators should plan for data-sharing agreements, return or destruction of data, and multiple regulatory approvals. Indigenous children must be included in clinical trials to reduce health disparities and improve health outcomes in these pediatric populations. Establishment of the Environmental Influences on Child Health Outcomes Institutional Development Award States Pediatric Clinical Trials Network (ECHO ISPCTN) in 2016 creates a unique and timely opportunity to increase Indigenous children's participation in state-of-the-art clinical trials.

Objectives: Home blood pressure monitoring (HBPM) is an important component of blood pressure (BP) management. We assessed performance of two HBPM devices among Alaska Native and American Indian people (ANAIs). Methods: We measured BP using Omron BP786 arm cuff, Omron BP654 wrist cuff, and Baum aneroid sphygmomanometer in 100 ANAIs. Performance was assessed with intraclass correlation, paired t -tests, and calibration models. Results: Compared to sphygmomanometer, average BP was higher for wrist cuff (systolic = 4.8 mmHg and diastolic = 3.6 mmHg) and varied for arm cuff (systolic = -1.5 mmHg and diastolic = 2.5 mmHg). Calibration increased performance from grade B to A for arm cuff and from D to B for wrist cuff. Calibration increased false negatives and decreased false positives. Discussion: The arm HBPM device is more accurate than the wrist cuff among ANAIs with hypertension. Most patients are willing to use the arm cuff when accuracy is discussed.

The frequencies of genetic variants in the CYP3A4 and CYP3A5 genes differ greatly across global populations, leading to profound differences in the metabolic activity of these enzymes and resulting drug metabolism rates, with important consequences for therapeutic safety and efficacy. Yet, the impact of genetic variants on enzyme activity are incompletely described, particularly in American Indian and Alaska Native (AIAN) populations. To characterize genetic variation in CYP3A4 and CYP3A5 and its effect on enzyme activity, we partnered with AIAN people living in two regions of Alaska: Yup'ik Alaska Native people living in the Yukon-Kuskokwim Delta region of rural southwest Alaska and AIAN people receiving care at the Southcentral Foundation in Anchorage, Alaska. We identified low frequencies of novel and known variation in CYP3A4 and CYP3A5, including low frequencies of the CYP3A4*1G and CYP3A5*1 variants, and linkage disequilibrium patterns that differed from those we previously identified in an American Indian population in western Montana. We also identified increased activity of the CYP3A4*1G allele in vitro and in vivo. We demonstrated that the CYP3A4*1G allele confers increased protein content in human lymphoblastoid cells and both increased protein content and increased activity in human liver microsomes. We confirmed enhanced CYP3A4-mediated 4β-vitamin D hydroxylation activity in Yup'ik people with the CYP3A4*1G allele. AIAN people in Alaska and Montana who carry the CYP3A4*1G allele-coupled with low frequency of the functional CYP3A5*1 variant-may metabolize CYP3A substrates more rapidly than people with the reference CYP3A4 allele., (© 2021 The Authors. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of the American Society for Clinical Pharmacology and Therapeutics.)

Vaginal tearing at childbirth is extremely common yet understudied despite the long-term serious consequences on women's health. The mechanisms of vaginal tearing remain unknown, and their knowledge could lead to the development of transformative prevention and treatment techniques for maternal injury. In this study, whole rat vaginas with pre-imposed elliptical tears oriented along the axial direction of the organs were pressurized using a custom-built inflation setup, producing large tear propagation. Large deformations of tears through propagation were analyzed, and nonlinear strains around tears were calculated using the digital image correlation technique. Second harmonic generation microscopy was used to examine collagen fiber organization in mechanically untested and tested vaginal specimens. Tears became increasingly circular under pressure, propagating slowly up to the maximum pressure and then more rapidly. Hoop strains were significantly larger than axial strains and displayed a region- and orientation-dependent response with tear propagation. Imaging revealed initially disorganized collagen fibers that aligned along the axial direction with increasing pressure. Fibers in the near-regions of tear tips aligned toward the hoop direction, hampering tear propagation. Changes in tear geometry, regional strains, and fiber orientation revealed the inherent toughening mechanisms of the vaginal tissue. STATEMENT OF SIGNIFICANCE: Women's reproductive health has historically been understudied despite alarming maternal injury and mortality rates in the world. Maternal injury and disability can be reduced by advancing our limited understanding of the large deformations experienced by women's reproductive organs. This manuscript presents, for the first time, the mechanics of tear propagation in vaginal tissue and changes to the underlying collagen microstructure near to and far from the tear. A novel inflation setup capable of maintaining the in vivo tubular geometry of the vagina while propagating a pre-imposed tear was developed. Toughening mechanisms of the vagina to propagation were examined through measurements of tear geometry, strain distributions, and reorientation of collagen fibers. This research draws from current advances in the engineering science and mechanics fields with the goal of improving maternal health care., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

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.

Although alcohol misuse is a priority for health care systems serving Alaska Native and American Indian (ANAI) people, stakeholders' perceptions of misuse are understudied. Patients ( n = 34), providers ( n = 20), and leaders ( n = 16) at a Tribally owned and operated health care system reported that alcohol misuse results from the interaction of factors, including colonization, structural factors, social alienation, social norms about overdrinking introduced at the time of colonizing contact, coping with emotions, and beliefs about ANAI people and alcohol. Childhood exposure to alcohol misuse leads some ANAI people to avoid alcohol altogether, shedding light on the high levels of abstinence observed in ANAI communities.

Background: For populations with high rates of trauma exposure yet low behavioural health service use, identifying and addressing trauma in the primary care setting could improve health outcomes, reduce disability and increase the efficiency of health system resources., Objective: To assess the acceptability and feasibility of a screening, brief intervention and referral to treatment (SBIRT) process for trauma and symptoms of posttraumatic stress disorder (PTSD) among American Indian and Alaska Native people. We also examine the short-term effects on service utilization and the screening accuracy of the Primary Care Posttraumatic Stress Disorder Screen., Methods: Cross-sectional pilot in two tribal primary care settings. Surveys and interviews measured acceptability among patients and providers. Health service utilization was used to examine impact. Structured clinical interview and a functional disability measure were used to assess screening accuracy., Results: Over 90% of patient participants (N = 99) reported the screening time was acceptable, the questions were easily understood, the right staff were involved and the process satisfactory. Ninety-nine percent would recommend the process. Participants screening positive had higher behavioural health utilization in the 3 months after the process than those screening negative. The Primary Care Posttraumatic Stress Disorder Screen was 100% sensitive to detect current PTSD with 51% specificity. Providers and administrators reported satisfaction with the process., Conclusions: The SBIRT process shows promise for identifying and addressing trauma in primary care settings. Future research should explore site specific factors, cost analyses and utility compared to other behavioural health screenings., (© The Author(s) 2019. Published by Oxford University Press. All rights reserved.For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: Alaska Native and American Indian (AN/AI) populations have higher tobacco use prevalence than other ethnic/racial groups. Pharmacogenetic testing to tailor tobacco cessation treatment may improve cessation rates. This study characterized polymorphic variations among AN/AI people in genes associated with metabolism of nicotine and drugs used for tobacco cessation., Methods: Recruitment of AN/AI individuals represented six subgroups, five geographic subgroups throughout Alaska and a subgroup comprised of AIs from the lower 48 states living in Alaska. We sequenced the CYP2A6 and CYP2B6 genes to identify known and novel gain, reduced, and loss-of-function alleles, including structural variation (eg, gene deletions, duplications, and hybridizations)., Results: Variant allele frequencies differed substantially between AN/AI subgroups. The gene deletion CYP2A6*4 and reduced function CYP2A6*9 alleles were found at high frequency in Northern/Western subgroups and in Lower 48/Interior subgroups, respectively. The reduced function CYP2B6*6 allele was observed in all subgroups and a novel, predicted reduced function CYP2B6 variant was found at relatively high frequency in the Southeastern subgroup., Conclusions: Diverse CYP2A6 and CYP2B6 variation among the subgroups highlight the need for comprehensive pharmacogenetic testing to guide tobacco cessation therapy for AN/AI populations., Implications: Nicotine metabolism is largely determined by CYP2A6 genotype, and variation in CYP2A6 activity has altered the treatment success in other populations. These findings suggest pharmacogenetic-guided smoking cessation drug treatment could provide benefit to this unique population seeking tobacco cessation therapy., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved.For permissions, please e-mail: journals.permissions@oup.com.)

Background: The literature on community-engaged research provides important principles to guide research partnerships, but concrete descriptions of the complexities involved in developing, navigating, and maintaining such partnerships are lacking., Objectives: To describe and assess a longstanding, complex research partnership between Indigenous and academic pharmacogenetic research partners, with attention to co-learning and capacity building lessons learned., Methods: Descriptive thematic analysis of 11 semistructured interviews with interdisciplinary research partners situated at Indigenous and academic settings., Results: Lessons learned included the need for explicit negotiation around mentoring expectations, and discussion on advisory and staff roles. Partners need to be aware not only of the structures, policies, and hierarchies within each partner institution, but also the tacit value commitments and understandings entailed in their different missions., Conclusions: This study highlights that the concept of "bidirectional" learning as it is usually presented in the literature fails to capture the complexity of how partnerships work.

Background: Posttraumatic stress disorder (PTSD) is a major public health concern among American Indian and Alaska Native populations. Primary care clinics are often the first point of contact for American Indian and Alaska Natives seeking health care and are feasible locations for trauma-focused interventions., Objective: Web-based therapeutic interventions have the potential to reduce PTSD symptoms by offering psychoeducation and symptom self-management tools. We investigated the feasibility of a culturally adapted Web-based therapeutic intervention in two American Indian and Alaska Native-serving primary care sites. We developed and tested a self-guided Web-based therapeutic intervention aimed at improving knowledge and awareness of, and provision of guidance, support, and symptom-management for, PTSD symptoms., Methods: A community-based participatory research process was used to refine adaptations to the veteran's administration's PTSD Coach Online, to develop new content, and to guide and interpret the results of the feasibility pilot. This process resulted in a 16-guide intervention "Health is Our Tradition: Balance and Harmony after Trauma" website. The feasibility pilot included 24 American Indian and Alaska Natives aged 18 years and older who scored positive on a primary care PTSD screener. Enrolled participants completed a demographic questionnaire, an experience with technology questionnaire, and baseline behavioral health measures. Once measures were complete, research staff described weekly text messages, minimum study expectations for website use, and demonstrated how to use the website. Feasibility measures included self-reported website use, ratings of satisfaction and perceived effectiveness, and website metrics. Feasibility of obtaining measures for an effectiveness trial was also assessed to include behavioral health symptoms and service utilization through self-report instruments and electronic health record queries. Self-reported measures were collected at enrollment and at 6 and 12 weeks post enrollment. Electronic health records were collected from 12 months before study enrollment to 3 months following study enrollment. Changes between enrollment and follow-up were examined with paired t tests, analysis of variance or logistic regression, or the Wilcoxon signed rank test for nonnormally distributed data., Results: The culturally adapted website and associated text message reminders were perceived as satisfactory and effective by participants with no differences by age or gender. The majority of participants (86%, 19/24) reported use of the website at 6 weeks and nearly all (91%, 20/22) at 12 weeks. At 6 weeks, 55% (12/22) of participants reported using the website at the recommended intensity (at least three times weekly), dropping to 36% (8/22) at 12 weeks. Participant use of modules varied from 8% (2/24) to 100% (24/24), with guide completion rates being greater for guides that were only psychoeducational in nature compared with guides that were interactive. There were no significant changes in patterns of diagnoses, screening, medications, or service utilization during exposure to the website., Conclusions: "Health is Our Tradition: Balance and Harmony after Trauma" shows promise for an effectiveness pilot., (©Vanessa Y Hiratsuka, Laurie Moore, Jaedon P Avey, Lisa G Dirks, Barbara D Beach, Denise A Dillard, Douglas K Novins. Originally published in JMIR Formative Research (http://formative.jmir.org), 13.11.2019.)

Precision medicine initiatives, such as Cancer Breakthrough 2020, promise to improve cancer outcomes by tailoring treatment to an individual's genes, environment, and lifestyle. This promise will fall short unless researchers successfully engage diverse communities, including those with histories of medical and research abuse. We examined a rural Alaska Native community's viewpoints about biospecimen collection and storage; interest and recall in reporting family health history; and interest and engagement in biospecimen collection for conducting a genetic test for cancer. In 2014, four focus groups were held with 28 adult Alaska Native rural community members. Thematic analysis was performed after establishing a coding scheme by team consensus. Study participants shared interest in engaging in genetic cancer research and suggested ways to improve community engagement in research. These included transparency and continuous communication with researchers at all stages of the research, clear communication about the intent of the research, and that research and results take into consideration the community's needs. These suggestions may be beneficial for future efforts to expand precision medicine research in Alaska Native communities and similar, diverse populations.

Alaska Native and American Indian (AN/AI) people have unique pharmacogene variation that may affect warfarin disposition and therapeutic response. We performed targeted genotyping for cytochrome P450 (CYP)2C9, vitamin K epoxide oxidase reductase complex subunit 1 (VKORC1), CYP4F2, CYP4F11, and gamma-glutamyl carboxylase (GGCX) variants in AN/AI people receiving warfarin. The primary outcome was stable warfarin dose, defined as one dose, and associated international normalized ratio within the target range, at least 6 months after starting therapy, with two matching doses at least 2 weeks apart. Genotype-phenotype relationships were assessed by multivariate regression analysis, adjusted for self-reported heritage, age, gender, and concurrent statin use. VKORC1 genotype explained 34% of dose variability, with VKORC1 -1639G>A and 1173C>T associated with a 1.7 mg/day (P = 1.4e-05) dose reduction. Additionally, CYP2C9 N218I was suggestively significant (P = 0.077), with heterozygotes requiring 1.1 mg/day less than reference individuals. Self-reported heritage was significantly associated with dose, largely driven by differences in the diagnostic VKORC1 allele frequencies among AN/AI people., (© 2018 The Authors. Clinical and Translational Science published by Wiley Periodicals, Inc. on behalf of the American Society for Clinical Pharmacology and Therapeutics.)

Background: Depression remains the second leading cause of disability worldwide. Symptoms of depression are expressed and experienced differently across cultural groups, impacting treatment decisions. Patient preferences predict service utilization, treatment selection and persistence, as well as health outcomes for medical and behavioral health conditions, including depression. We identified depression management preferences of Alaska Native and American Indian (AN/AI) people who receive care within a comprehensive, integrated, tribally owned and operated healthcare facility in Anchorage, Alaska., Methods: Adult AN/AI patients who screened positive for depression (10 or greater on the Patient Health Questionnaire - 9 (PHQ-9)) completed a culturally-tailored decision-support tool to assess their depression management interests., Results: The 125 eligible patients, who screened positive for depression, preferred counseling and medications to peer support groups, herbal remedies, and spiritual support. Those 18-39 years of age were more likely to prefer medications and less likely to prefer spirituality and peer support than those 40 years of age and older. Patients with moderate and severe depression were more likely to prefer exercise, healthy eating, and stress reduction than individuals with mild depression., Limitations: Women comprised 78% of the sample. Responses may not adequately represent the views of men., Conclusions: Counseling and medications should consistently be made available earlier in the course of depression management. Patient interest in exercise, stress reduction, and healthy eating to manage depression, especially among those with moderate and severe depression, offers opportunity for additional collaboration in an integrated care setting., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Few advanced mechanics of materials solutions have found broader and more enduring applications than Emil Winkler's beam on elastic foundation analysis, first published in 1867. Now, 150 years after its introduction, this concept continues to enjoy widespread use in its original application field of civil engineering, and has also had a profound effect on the field of adhesion mechanics, including for soft matter adhesion phenomena. A review of the model is presented with a focus on applications to adhesion science, highlighting classical works that utilize the model as well as recent usages that extend its scope. The special case of the behavior of plates on incompressible (e.g., elastomeric and viscous liquid) foundations is reviewed because of the significant relevance to the behavior of soft matter interlayers between one or more flexible adherends.

Despite evidence that pharmacogenetics can improve tamoxifen pharmacotherapy, there are few studies with American Indian and Alaska Native (AIAN) people. We examined variation in cytochrome P450 (CYP) genes (CYP2D6, CYP3A4, CYP3A5, and CYP2C9) and tamoxifen biotransformation in AIAN patients with breast cancer (n = 42) from the Southcentral Foundation in Alaska and the Confederated Salish and Kootenai Tribes in Montana. We tested for associations between CYP diplotypes and plasma concentrations of tamoxifen and metabolites. Only the CYP2D6 variation was significantly associated with concentrations of endoxifen (P = 0.0008) and 4-hydroxytamoxifen (P = 0.0074), tamoxifen's principal active metabolites, as well as key metabolic ratios. The CYP2D6 was also the most significant predictor of active metabolites and metabolic ratios in a multivariate regression model, including all four genes as predictors, with minor roles for other CYP genes. In AIAN populations, CYP2D6 is the largest contributor to tamoxifen bioactivation, illustrating the importance of validating pharmacogenetic testing for therapy optimization in an understudied population., (© 2018 The Authors. Clinical and Translational Science published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.)

In May 2016, Southcentral Foundation (SCF), a regional tribal health corporation based in Anchorage, Alaska convened a half-day health research forum for Alaska Native and American Indian community members to obtain feedback on communication of research findings. Thirty one individuals attended the Forum and 22 completed a pre and post survey. Respondents found the Forum to be a useful method to learn about research projects and their willingness to participate in health research reportedly increased because of the event. Forum attendees also endorsed use of direct mail, electronic mail, and messages via an electronic health record patient portal as communication methods for health researchers to inform potential participants about research studies occurring at SCF and for return of individual and community level results.

Alaska Native and American Indian (AN/AI) people experience a disproportionate burden of health disparities in the United States. Including AN/AI people in pharmacogenetic research offers an avenue to address these health disparities, however the dissemination of pharmacogenetic research results in the community context can be a challenging task. In this paper, we describe a case-study that explores the preferences of AN/AI community members regarding pharmacogenetic research results dissemination. Results were presented as a PowerPoint presentation at the 2016 Alaska Native Health Research Forum (Forum). An audience response system and discussion groups were used to gather feedback from participants. Descriptive statistics were used to assess attendee understanding of the presentation content. Thematic analysis was used to analyze discussion group data. Forum attendees needed time to work through the concept of pharmacogenetics and looked for ways pharmacogenetics could apply to their daily life. Attendees found pharmacogenetics interesting, but wanted a simple description of pharmacogenetics. Community members were optimistic about the potential benefit pharmacogenetic medicine could have in the delivery of health care and expressed excitement this research was taking place. Researchers were urged to communicate throughout the study, not just end research results, to the community. Furthermore, attendees insisted their providers stay informed of research results that may have an impact on health care delivery. Conversational forms of dissemination are recommended when disseminating pharmacogenetic research results at the community level.

Alaska Native and American Indian (AN/AI) people have negative research experiences, including lack of timely, respectful, and relevant communication about research findings. Southcentral Foundation (SCF), a tribally owned and operated health care organization in Alaska, has redesigned the health care system, enacted research policies, and established a research department which uses best practices of Community Engaged Research with AN/AI people. Department staff and community members, however, perceive significant limitations in the reach of and satisfaction with ongoing engagement and dissemination efforts. Background information is delineated which supports new approaches in research engagement using SCF as an example.

Southcentral Foundation, a tribal health organization serving Alaska Native and American Indian (AN/AI) people in southcentral Alaska, convened the Alaska Native Health Research Forum (Forum) for AN/AI people in May 2016. The purpose of the Forum was to obtain AN/AI community member feedback about sharing health research results. This article describes the funding mechanism that provided resources for the Forum and other factors that were considered when designing the Forum. This is followed by a description of how attendees were invited, the audience response system, and process used to collect quantitative data on participants and qualitative feedback from small group discussions with Forum attendees. Finally, we describe the quantitative and qualitative data analysis processes used to evaluate responses.

Exposure to trauma is consistently associated with co-occurrence of behavioral health disorders. Primary care settings are opportune places to screen for traumatic experiences and symptoms, as they are often the initial point of care for behavioral health concerns by the Alaska Native and American Indian (AN/AI) population. In this case study, we examine results dissemination activities at the SCF Research Department-hosted 2016 Alaska Native Health Research Forum (Forum) of a pilot study of a trauma-focused screening, brief intervention, and referral to treatment (T-SBIRT) process for AN/AI adults in primary care. Feedback included audience responses to the presentation delivered at the Forum and recommendations to guide future community dissemination of T-SBIRT results. Attendees (N = 31) found the presentation clear, interesting, and included the right amount of detail. Four broad dissemination themes were identified in discussion groups: 1) share results with everyone; 2) share results in ways that reach all AN audiences; 3) provide a summarized status update at each stage of the study; and 4) use results to improve care for trauma and related symptoms.