Returning personalized, genetic health test results to individuals of African descent or ancestry in precision medicine research.

Today, many epidemiological studies and biobanks are offering to disclose individual genetic results to their participants, including the National Institutes of Health's All of Us Research Program. Returning hereditary disease risks and pharmacogenetic test results to study participants from racial/ethnic groups that are historically underrepresented in biomedical research poses specific challenges to those participants and the health system writ large. For example, individuals of African descent are underrepresented in research about drug-gene interactions and have a relatively higher proportion of variants of unknown significance, affecting their ability to take clinical action following return of results. In this brief report, we summarize studies published to date concerning the perspectives and/or attitudes of African Americans engaged in genetic research programs to anticipate factors in disclosure protocols that would minimize risks and maximize benefits. A thematic analysis of studies identified (n = 6) lends to themes centered on motivations to engage or disengage in the return of results and integrating research and care. Actionable strategies determined in reaction to these themes center on ensuring adequate system and health education support for participants and personalizing the process for participants engaging in return of results. Overall, we offer these themes and actionable strategies as early guidance to research programs, and provide recommendations to policy makers focused on fair and equitable return of genetic research results to underrepresented research participants.

Association of Medicaid expansion with 2-year survival and time to treatment initiation in gastrointestinal cancer patients: A National Cancer Database study.

INTRODUCTION: We evaluated whether Medicaid expansion (ME) was associated with improved 2-year survival and time to treatment initiation (TTI) among patients with gastrointestinal (GI) cancer. METHODS: GI cancer patients diagnosed 40-64 years were queried from the National Cancer Database. Those diagnosed from 2010 to 2012 were considered pre-expansion; those diagnosed from 2014 to 2016 were considered post-expansion. Cox models estimated hazard ratios and 95% confidence intervals (CIs) for 2-year overall survival. Generalized estimating equations (GEE) estimated odds ratios (OR) and 95% CI of TTI within 30- and 90 days. Multivariable Difference-in-Difference models were used to compare expansion/nonexpansion cohorts pre-/post-expansion, adjusting for patient, clinical, and hospital factors. RESULTS: 377,063 patients were included. No significant difference in 2-year survival was demonstrated across ME and non-ME states overall or in site-based subgroup analysis. In stage-based subgroup analysis, 2-year survival significantly improved among stage II cancer, with an 8% decreased hazard of death at 2 years (0.92; 0.87-0.97). Those with stage IV had a 4% increased hazard of death at 2 years (1.04; 1.01-1.07). Multivariable GEE models showed increased TTI within 30 days (1.12; 1.09-1.16) and 90 days (1.22; 1.17-1.27). Site-based subgroup analyses indicated increased likelihood of TTI within 30 and 90 days among colon, liver, pancreas, rectum, and stomach cancers, by 30 days for small intestinal cancer, and by 90 days for esophageal cancer. In subgroup analyses, all stages experienced improved odds of TTI within 30 and 90 days. CONCLUSION: ME was not associated with significant improvement in 2-year survival for those with GI cancer. Although TTI increased after ME for both cohorts, the 30- and 90-day odds of TTI was higher for those from ME compared with non-ME states. Our findings add to growing evidence of associations with ME for those diagnosed with GI cancer.

The Curiosity Rover's Exploration of Glen Torridon, Gale Crater, Mars: An Overview of the Campaign and Scientific Results.

The Mars Science Laboratory rover, Curiosity, explored the clay mineral-bearing Glen Torridon region for 1 Martian year between January 2019 and January 2021, including a short campaign onto the Greenheugh pediment. The Glen Torridon campaign sought to characterize the geology of the area, seek evidence of habitable environments, and document the onset of a potentially global climatic transition during the Hesperian era. Curiosity roved 5 km in total throughout Glen Torridon, from the Vera Rubin ridge to the northern margin of the Greenheugh pediment. Curiosity acquired samples from 11 drill holes during this campaign and conducted the first Martian thermochemolytic-based organics detection experiment with the Sample Analysis at Mars instrument suite. The lowest elevations within Glen Torridon represent a continuation of lacustrine Murray formation deposits, but overlying widespread cross bedded sandstones indicate an interval of more energetic fluvial environments and prompted the definition of a new stratigraphic formation in the Mount Sharp group called the Carolyn Shoemaker formation. Glen Torridon hosts abundant phyllosilicates yet remains compositionally and mineralogically comparable to the rest of the Mount Sharp group. Glen Torridon samples have a great diversity and abundance of sulfur-bearing organic molecules, which are consistent with the presence of ancient refractory organic matter. The Glen Torridon region experienced heterogeneous diagenesis, with the most striking alteration occurring just below the Siccar Point unconformity at the Greenheugh pediment. Results from the pediment campaign show that the capping sandstone formed within the Stimson Hesperian aeolian sand sea that experienced seasonal variations in wind direction.

Orbital and In-Situ Investigation of Periodic Bedrock Ridges in Glen Torridon, Gale Crater, Mars.

Gale crater, the field site for NASA's Mars Science Laboratory Curiosity rover, contains a diverse and extensive record of aeolian deposition and erosion. This study focuses on a series of regularly spaced, curvilinear, and sometimes branching bedrock ridges that occur within the Glen Torridon region on the lower northwest flank of Aeolis Mons, the central mound within Gale crater. During Curiosity's exploration of Glen Torridon between sols ∼2300-3080, the rover drove through this field of ridges, providing the opportunity for in situ observation of these features. This study uses orbiter and rover data to characterize ridge morphology, spatial distribution, compositional and material properties, and association with other aeolian features in the area. Based on these observations, we find that the Glen Torridon ridges are consistent with an origin as wind-eroded bedrock ridges, carved during the exhumation of Mount Sharp. Erosional features like the Glen Torridon ridges observed elsewhere on Mars, termed periodic bedrock ridges (PBRs), have been interpreted to form transverse to the dominant wind direction. The size and morphology of the Glen Torridon PBRs are consistent with transverse formative winds, but the orientation of nearby aeolian bedforms and bedrock erosional features raise the possibility of PBR formation by a net northeasterly wind regime. Although several formation models for the Glen Torridon PBRs are still under consideration, and questions persist about the nature of PBR-forming paleowinds, the presence of PBRs at this site provides important constraints on the depositional and erosional history of Gale crater.

African American Nurses' Perspectives on Genomic Medicine Research.

Background: There is a lack of African American (AA) community engagement in genomic medicine research. Recent popular interest in the experience of AAs, such as that of Henrietta Lacks, has perhaps prompted interest in research on how AA nurses can provide strategies to better engage AA communities in genomic medicine research. Methods: The authors conducted one-on-one semi-structured interviews with 11 National Black Nurses Association (NBNA) chapter leaders from 8 different US states, representing 782 NBNA members. Results: Our results quantified NBNA chapter leader agreement on known themes from the literature, captured newly emerging themes, and produced a set of actionable strategies to help overcome barriers to AA engagement in genomic medicine research that fall under 6 themes: (1) engagement, support, information dissemination, and implementation recommendations in general and to address health disparities; (2) addressing language barriers; (3) addressing research implementation barriers; (4) getting physicians to participate; (5) overcoming privacy concerns; and (6) nursing education recommendations. Conclusions: Actionable strategies presented herein can help researchers better engage AA communities in genomic medicine research.

Level of Comfort With Pediatric Trauma Transports: Survey of Prehospital Providers.

BACKGROUND: Unintentional injury is the leading cause of death in pediatric patients. Despite a heavy burden of pediatric trauma, prehospital transport and triage of pediatric trauma patients are not standardized. Prehospital providers report anxiety and a lack of confidence in transport, triage, and care of pediatric trauma patients. MATERIALS AND METHODS: Prehospital transport providers with 3 organizations across southeast Georgia and northeast Florida were contacted via email (n = 146) and asked to complete 2 Web-based surveys to evaluate their comfort level with performing tasks in the transport of pediatric and adult trauma patients. Bivariate statistics and qualitative thematic analyses were performed to assess comfort with pediatric trauma transports. RESULTS: Survey 1 (N = 35) showed that mean comfort levels of prehospital providers were significantly lower for pediatric patients than adult trauma patients in 7 out of 9 tasks queried, including airway management and interpreting children's physiology. The following themes emerged from survey 2 (N = 14) responses: additional clinical knowledge resources would be beneficial when caring for pediatric trauma patients, pediatric medication administration is a source of uncertainty, prehospital transport teams would benefit from additional pediatric trauma training, infrequent transport of pediatric trauma patients affects provider comfort level, and pediatric trauma generates higher levels of anxiety among providers. DISCUSSION: Prehospital transport of pediatric trauma patients is infrequent and a source of anxiety for prehospital providers. Rigs should be equipped with a reference tool addressing crucial tasks and deficiencies in training.

Diagenesis of Vera Rubin Ridge, Gale Crater, Mars, From Mastcam Multispectral Images.

Images from the Mars Science Laboratory (MSL) mission of lacustrine sedimentary rocks of Vera Rubin ridge on "Mt. Sharp" in Gale crater, Mars, have shown stark color variations from red to purple to gray. These color differences crosscut stratigraphy and are likely due to diagenetic alteration of the sediments after deposition. However, the chemistry and timing of these fluid interactions is unclear. Determining how diagenetic processes may have modified chemical and mineralogical signatures of ancient Martian environments is critical for understanding the past habitability of Mars and achieving the goals of the MSL mission. Here we use visible/near-infrared spectra from Mastcam and ChemCam to determine the mineralogical origins of color variations in the ridge. Color variations are consistent with changes in spectral properties related to the crystallinity, grain size, and texture of hematite. Coarse-grained gray hematite spectrally dominates in the gray patches and is present in the purple areas, while nanophase and fine-grained red crystalline hematite are present and spectrally dominate in the red and purple areas. We hypothesize that these differences were caused by grain-size coarsening of hematite by diagenetic fluids, as observed in terrestrial analogs. In this model, early primary reddening by oxidizing fluids near the surface was followed during or after burial by bleaching to form the gray patches, possibly with limited secondary reddening after exhumation. Diagenetic alteration may have diminished the preservation of biosignatures and changed the composition of the sediments, making it more difficult to interpret how conditions evolved in the paleolake over time.

Extraformational sediment recycling on Mars.

Extraformational sediment recycling (old sedimentary rock to new sedimentary rock) is a fundamental aspect of Earth's geological record; tectonism exposes sedimentary rock, whereupon it is weathered and eroded to form new sediment that later becomes lithified. On Mars, tectonism has been minor, but two decades of orbiter instrument-based studies show that some sedimentary rocks previously buried to depths of kilometers have been exposed, by erosion, at the surface. Four locations in Gale crater, explored using the National Aeronautics and Space Administration's Curiosity rover, exhibit sedimentary lithoclasts in sedimentary rock: At Marias Pass, they are mudstone fragments in sandstone derived from strata below an erosional unconformity; at Bimbe, they are pebble-sized sandstone and, possibly, laminated, intraclast-bearing, chemical (calcium sulfate) sediment fragments in conglomerates; at Cooperstown, they are pebble-sized fragments of sandstone within coarse sandstone; at Dingo Gap, they are cobble-sized, stratified sandstone fragments in conglomerate derived from an immediately underlying sandstone. Mars orbiter images show lithified sediment fans at the termini of canyons that incise sedimentary rock in Gale crater; these, too, consist of recycled, extraformational sediment. The recycled sediments in Gale crater are compositionally immature, indicating the dominance of physical weathering processes during the second known cycle. The observations at Marias Pass indicate that sediment eroded and removed from craters such as Gale crater during the Martian Hesperian Period could have been recycled to form new rock elsewhere. Our results permit prediction that lithified deltaic sediments at the Perseverance (landing in 2021) and Rosalind Franklin (landing in 2023) rover field sites could contain extraformational recycled sediment.

Exploring African American community perspectives about genomic medicine research: A literature review.

Genomic medicine research is an important topic in the African American health care community. African American nurses and advance practice nursing professionals are poised to encourage and educate themselves and their communities about the importance of diversity in genomic medicine research. The Southern Nevada Black Nurses Association, a chapter within the larger National Black Nurses Association's, recently engaged in the National Institutes of Health All of Us research program to educate their members about formularies and other treatment modalities that could clinically benefit African-Americans and other populations of color. During this event, the Southern Nevada Black Nurses Association discovered that National Black Nurses Association members held ethical, legal, and social concerns about engaging in genomic medicine research that align with respective concerns reported in the literature. In this review, we discuss National Black Nurses Association concerns and how they relate to qualitative themes emerging from the literature and a recent National Academies of Science, Engineering, and Medicine event on disparities in access to genomic medicine. We conclude that researchers should engage with African American health community leaders to effectively engage the African American community in genomic medicine research and help ensure that genomic medicine does not exacerbate existing health disparities.

Molecular Pathways Underlying Adaptive Repair of the Injured Kidney: Novel Donation After Cardiac Death and Acute Kidney Injury Platforms.

OBJECTIVE: To test the hypothesis that gene expression profiling in peripheral blood from patients who have undergone kidney transplantation (KT) will provide mechanistic insights regarding graft repair and regeneration. BACKGROUND: Renal grafts obtained from living donors (LD) typically function immediately, whereas organs from donation after cardiac death (DCD) or acute kidney injury (AKI) donors may experience delayed function with eventual recovery. Thus, recipients of LD, DCD, and AKI kidneys were studied to provide a more complete understanding of the molecular basis for renal recovery. METHODS: Peripheral blood was collected from LD and DCD/AKI recipients before transplant and throughout the first 30 days thereafter. Total RNA was isolated and assayed on whole genome microarrays. RESULTS: Comparison of longitudinal gene expression between LD and AKI/DCD revealed 2 clusters, representing 141 differentially expressed transcripts. A subset of 11 transcripts was found to be differentially expressed in AKI/DCD versus LD. In all recipients, the most robust gene expression changes were observed in the first day after transplantation. After day 1, gene expression profiles differed depending upon the source of the graft. In patients receiving LD grafts, the expression of most genes did not remain markedly elevated beyond the first day post-KT. In the AKI/DCD groups, elevations in gene expression were maintained for at least 5 days post-KT. In all recipients, the pattern of coordinate gene overexpression subsided by 28 to 30 days. CONCLUSIONS: Gene expression in peripheral blood of AKI/DCD recipients offers a novel platform to understand the potential mechanisms and timing of kidney repair and regeneration after transplantation.

Utility of extracellular matrix powders in tissue engineering.

Extracellular matrix (ECM) materials have had remarkable success as scaffolds in tissue engineering (TE) and as therapies for tissue injury whereby the ECM microenvironment promotes constructive remodeling and tissue regeneration. ECM powder and solubilized derivatives thereof have novel applications in TE and RM afforded by the capacity of these constructs to be dynamically modulated. The powder form allows for effective incorporation and penetration of reagents; hence, ECM powder is an efficacious platform for 3D cell culture and vehicle for small molecule delivery. ECM powder offers minimally invasive therapy for tissue injury and successfully treatment for wounds refractory to first-line therapies. Comminution of ECM and fabrication of powder-derived constructs, however, may compromise the biological integrity of the ECM. The current lack of optimized fabrication protocols prevents a more extensive and effective clinical application of ECM powders. Further study on methods of ECM powder fabrication and modification is needed.

Regenerative immunology: the immunological reaction to biomaterials.

Regenerative medicine promises to meet two of the most urgent needs of modern organ transplantation, namely immunosuppression-free transplantation and an inexhaustible source of organs. Ideally, bioengineered organs would be manufactured from a patient's own biomaterials-both cells and the supporting scaffolding materials in which cells would be embedded and allowed to mature to eventually regenerate the organ in question. While some groups are focusing on the feasibility of this approach, few are focusing on the immunogenicity of the scaffolds that are being developed for organ bioengineering purposes. This review will succinctly discuss progress in the understanding of immunological characteristics and behavior of different scaffolds currently under development, with emphasis on the extracellular matrix scaffolds obtained decellularized animal or human organs which seem to provide the ideal template for bioengineering purposes.

Extracellular matrix scaffolds as a platform for kidney regeneration.

Chronic and end stage renal disease (ESRD) have reached pandemic levels and pose a substantial public health burden. Unfortunately, available therapies lack efficacy in preventing progression to its end stage phase. Regenerative medicine promises to restore function of diseased organs among which the kidney, through two possible approaches: firstly, the maximization of the innate ability of tissues to repair or regenerate following injury; secondly, the ex vivo bio-fabrication of the organ in question. When regenerative medicine is applied to the setting of chronic or ESRD, it is intuitive that endeavors to improve renal repair, promote nephrogenesis in damaged kidneys, or the de novo engineering of transplantable kidneys, could have a major impact on the current management of this pandemic. Among the different regenerative medicine technologies currently under development, cell-on-scaffold seeding technology (CSST) - involving cells seeded throughout supporting scaffold structures made from biomaterials - is the most favorable candidate in the context of realistic clinical application. In this review, we outline and describe current investigations taking place in the field of CSST as it pertains to the restoration of kidney function.

Kidney transplantation, bioengineering and regeneration: an originally immunology-based discipline destined to transition towards ad hoc organ manufacturing and repair.

Kidney transplantation (KT), as a modality of renal replacement therapy (RRT), has been shown to be both economically and functionally superior to dialysis for the treatment of end-stage renal disease (ESRD). Progress in KT is limited by two major barriers: a) a chronic and burgeoning shortage of transplantable organs and b) the need for chronic immunosuppression following transplantation. Although ground-breaking advances in transplant immunology have improved patient survival and graft durability, a new pathway of innovation is needed in order to overcome current obstacles. Regenerative medicine (RM) holds the potential to shift the paradigm in RRT, through organ bioengineering. Manufactured organs represent a potentially inexhaustible source of transplantable grafts that would bypass the need for immunosuppressive drugs by using autologous cells to repopulate extracellular matrix (ECM) scaffolds. This overview discusses the current status of renal transplantation while reviewing the most promising innovations in RM therapy as applied to RRT.

Heterogeneity of Scaffold Biomaterials in Tissue Engineering.

Tissue engineering (TE) offers a potential solution for the shortage of transplantable organs and the need for novel methods of tissue repair. Methods of TE have advanced significantly in recent years, but there are challenges to using engineered tissues and organs including but not limited to: biocompatibility, immunogenicity, biodegradation, and toxicity. Analysis of biomaterials used as scaffolds may, however, elucidate how TE can be enhanced. Ideally, biomaterials should closely mimic the characteristics of desired organ, their function and their in vivo environments. A review of biomaterials used in TE highlighted natural polymers, synthetic polymers, and decellularized organs as sources of scaffolding. Studies of discarded organs supported that decellularization offers a remedy to reducing waste of donor organs, but does not yet provide an effective solution to organ demand because it has shown varied success in vivo depending on organ complexity and physiological requirements. Review of polymer-based scaffolds revealed that a composite scaffold formed by copolymerization is more effective than single polymer scaffolds because it allows copolymers to offset disadvantages a single polymer may possess. Selection of biomaterials for use in TE is essential for transplant success. There is not, however, a singular biomaterial that is universally optimal.

Tissue-Engineering Approaches to Restore Kidney Function.

Kidney transplantation for the treatment of chronic kidney disease has established outcome and quality of life. However, its implementation is severely limited by a chronic shortage of donor organs; consequently, most candidates remain on dialysis and on the waiting list while accruing further morbidity and mortality. Furthermore, those patients that do receive kidney transplants are committed to a life-long regimen of immunosuppressive drugs that also carry significant adverse risk profiles. The disciplines of tissue engineering and regenerative medicine have the potential to produce alternative therapies which circumvent the obstacles posed by organ shortage and immunorejection. This review paper describes some of the most promising tissue-engineering solutions currently under investigation for the treatment of acute and chronic kidney diseases. The various stem cell therapies, whole embryo transplantation, and bioengineering with ECM scaffolds are outlined and summarized.

Health-care professionals' attitudes across different hospital departments regarding alcohol-related presentations.

INTRODUCTION AND AIMS: Attitudes to individuals presenting with alcohol-related issues are important in developing therapeutic relationships and applying alcohol-related interventions. This study explores staff attitudes to these individuals across a range of roles and departments. DESIGN AND METHODS: Data were gathered from 204 staff in the Southern Health and Social Care Trust in Northern Ireland. Regression models were used to predict attitudes as measured by the Short Alcohol and Alcohol Problems Perception Questionnaire (SAAPPQ). RESULTS: Two hundred and four people participated in the study. The sample comprised doctors, nurses, allied health professionals and other staff who had face-to-face contact with patients. Staff worked in accident and emergency (A&E), medical, surgical, addiction or psychiatry departments. Staff working in addiction and psychiatry departments had significantly higher levels of role adequacy compared with those in A&E. Staff in addictions also demonstrated higher levels of role legitimacy, motivation and role satisfaction than those in A&E. Doctors had higher role adequacy and role legitimacy than nursing staff. DISCUSSION AND CONCLUSIONS: There are critical differences in staff attitudes to patients presenting with alcohol-related issues in a range of hospital settings; training and working in a specialist setting have a significant positive influence on staff attitudes. This suggests that further training and support would positively enhance the attitudes of staff in a variety of professional roles and across a range of hospital settings in the management of patients presenting with alcohol-related difficulties. [Iqbal N, McCambridge O, Edgar L, Young C, Shorter GW. Health-care professionals' attitudes across different hospital departments regarding alcohol-related presentations. Drug Alcohol Rev 2015;34:487-94].