15 results on '"M Jeske"'
Search Results
2. Marginalized measures: The harmonization of diversity in precision medicine research.
- Author
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Jeske M, Saperstein A, Lee SS, and Shim JK
- Abstract
The production of large, shareable datasets is increasingly prioritized for a wide range of research purposes. In biomedicine, especially in the United States, calls to enhance representation of historically underrepresented populations in databases that integrate genomic, health history, demographic and lifestyle data have also increased in order to support the goals of precision medicine. Understanding the assumptions and values that shape the design of such datasets and the practices through which they are constructed are a pressing area of social inquiry. We examine how diversity is conceptualized in U.S. precision medicine research initiatives, specifically attending to how measures of diversity, including race, ethnicity, and medically underserved status, are constructed and harmonized to build commensurate datasets. In three case studies, we show how symbolic embrace of both diversity and harmonization efforts can compromise the utility of diversity data. Although big data and diverse population representation are heralded as the keys to unlocking the promises of precision medicine research, these cases reveal core tensions between what kinds of data are seen as central to 'the science' and which are marginalized.
- Published
- 2024
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3. Development and validation of a national clinical pharmacy competency framework for hospital pharmacists in Austria: a multi-method study.
- Author
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Stoll JT, Böhmdorfer-McNair B, Jeske M, and Weidmann AE
- Abstract
Background: Despite the publication of a European wide competency framework for hospital pharmacy by the European Association of Hospital Pharmacist (EAHP) in 2017, not all countries have adopted and implemented such a framework., Aim: This study aimed to develop and validate a bespoke national hospital pharmacy competency framework for Austria that supports the hospital pharmacy workforce development., Method: A multi-method study was carried out in three phases. (I) A systematic literature review across 48 websites of healthcare-related associations and six scientific databases was conducted, identifying competency frameworks, guidelines and related documents. (II) Extracted behaviour competencies were reviewed for contextual national appropriateness by three researchers prior to mapping against the "Patient Care and Clinical Pharmacy Skills" domain of European Common Training Framework (CTF). (III) Validation of the resultant draft clinical skills competency framework took place by an expert panel (n = 4; Austrian Association of Hospital Pharmacists (AAHP) board members) discussion. Reporting of findings is aligned with the recommendations for reporting Competency Framework Development in health professions (CONFERD-HP guidelines) and the PRISMA 2020 checklist., Results: The systematic review (SR) resulted in 28 frameworks, guidelines and related documents and the identification of 379 behaviour competencies, with nineteen mapped to the "Patient Care and Clinical Pharmacy Skills" domain of the CTF (after removal of duplicates). Expert panel discussion resulted in suggested changes to ensure contextual national appropriateness., Conclusion: This study resulted in the development and validation of the first clinical national pharmacy competency framework for Austria. Future studies should focus on political and practical structures necessary for its successful implementation., (© 2024. The Author(s).)
- Published
- 2024
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4. Automated Non-Sterile Pharmacy Compounding: A Multi-Site Study in European Hospital and Community Pharmacies with Pediatric Immediate Release Propranolol Hydrochloride Tablets.
- Author
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Sandler Topelius N, Shokraneh F, Bahman M, Lahtinen J, Hassinen N, Airaksinen S, Verma S, Hrizanovska L, Lass J, Paaver U, Tähnas J, Kern C, Lagarce F, Fenske D, Malik J, Scherliess H, Cruz SP, Paulsson M, Dekker J, Kammonen K, Rautamo M, Lück H, Pierrot A, Stareprawo S, Tubic-Grozdanis M, Zibolka S, Lösch U, Jeske M, Griesser U, Hummer K, Thalmeier A, Harjans A, Kruse A, Heimke-Brinck R, Khoukh K, and Bruno F
- Abstract
Pharmacy compounding, the art and science of preparing customized medications to meet individual patient needs, is on the verge of transformation. Traditional methods of compounding often involve manual and time-consuming processes, presenting challenges in terms of consistency, dosage accuracy, quality control, contamination, and scalability. However, the emergence of cutting-edge technologies has paved a way for a new era for pharmacy compounding, promising to redefine the way medications are prepared and delivered as pharmacy-tailored personalized medicines. In this multi-site study, more than 30 hospitals and community pharmacies from eight countries in Europe utilized a novel automated dosing approach inspired by 3D printing for the compounding of non-sterile propranolol hydrochloride tablets. CuraBlend
® excipient base, a GMP-manufactured excipient base (pharma-ink) intended for automated compounding applications, was used. A standardized study protocol to test the automated dosing of tablets with variable weights was performed in all participating pharmacies in four different iterative phases. Integrated quality control was performed with an in-process scale and NIR spectroscopy supported by HPLC content uniformity measurements. In total, 6088 propranolol tablets were produced at different locations during this study. It was shown that the dosing accuracy of the process increased from about 90% to 100% from Phase 1 to Phase 4 by making improvements to the formulation and the hardware solutions. The results indicate that through this automated and quality controlled compounding approach, extemporaneous pharmacy manufacturing can take a giant leap forward towards automation and digital manufacture of dosage forms in hospital pharmacies and compounding pharmacies.- Published
- 2024
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5. ReLo is a simple and rapid colocalization assay to identify and characterize direct protein-protein interactions.
- Author
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Salgania HK, Metz J, and Jeske M
- Subjects
- Protein Interaction Mapping methods, Proteins metabolism
- Abstract
The characterization of protein-protein interactions (PPIs) is fundamental to the understanding of biochemical processes. Many methods have been established to identify and study direct PPIs; however, screening and investigating PPIs involving large or poorly soluble proteins remains challenging. Here, we introduce ReLo, a simple, rapid, and versatile cell culture-based method for detecting and investigating interactions in a cellular context. Our experiments demonstrate that ReLo specifically detects direct binary PPIs. Furthermore, we show that ReLo bridging experiments can also be used to determine the binding topology of subunits within multiprotein complexes. In addition, ReLo facilitates the identification of protein domains that mediate complex formation, allows screening for interfering point mutations, and it is sensitive to drugs that mediate or disrupt an interaction. In summary, ReLo is a simple and rapid alternative for the study of PPIs, especially when studying structurally complex proteins or when established methods fail., (© 2024. The Author(s).)
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- 2024
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6. Interrogating the Value of Return of Results for Diverse Populations: Perspectives from Precision Medicine Researchers.
- Author
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McMahon CE, Foti N, Jeske M, Britton WR, Fullerton SM, Shim JK, and Lee SS
- Subjects
- Humans, Cultural Diversity, Biomedical Research ethics, Research Subjects, Disclosure, Qualitative Research, Precision Medicine, Research Personnel
- Abstract
Background: Over the last decade, the return of results (ROR) in precision medicine research (PMR) has become increasingly routine. Calls for individual rights to research results have extended the "duty to report" from clinically useful genetic information to traits and ancestry results. ROR has thus been reframed as inherently beneficial to research participants, without a needed focus on who benefits and how. This paper addresses this gap, particularly in the context of PMR aimed at increasing participant diversity, by providing investigator and researcher perspectives on and questions about the assumed value of ROR in PMR., Methods: Semi-structured interviews with a purposive sample of investigators and researchers across federally funded PMR studies in three national consortia, as well as observations of study activities, focused on how PM researchers conceptualize diversity and implement inclusive practices across research stages, including navigating ROR., Results: Interviewees (1) validated the value of ROR as a benefit of PMR, while others (2) questioned the benefit of clinically actionable results to individuals in the absence of sufficient resources for translating findings into health care for diverse and disadvantaged populations; (3) expressed uncertainties in applying the presumed value of ROR as a benefit for non- clinical results; and (4) and debated when the promise of the value of ROR may undermine trust in PMR, and divert efforts to return value beyond ROR., Conclusions: Conceptualizations of diversity and inclusion among PM researchers and investigators raise unique ethical questions where unexamined assumptions of the value of ROR inform study recruitment efforts to enroll minoritized and under-represented populations. A lack of consideration for resources and infrastructure necessary to translate ROR into actionable information may hinder trustworthy community-research relationships. Thus, we argue for a more intentional interrogation of ROR practices as an offer of benefit and for whom.
- Published
- 2024
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7. Diagnosis and the practices of patienthood: How diagnostic journeys shape illness experiences.
- Author
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Jeske M, James J, and Joyce K
- Subjects
- Humans, Female, Qualitative Research, Health Personnel, Sociology, Breast Neoplasms
- Abstract
Sociologists have a rich history of studying the process of diagnosis and how people experience illness. Yet, the sociology of diagnosis and illness experience literatures have seldom been fully integrated. Instead, these literatures highlight one element of the illness journey, wherein scholars either primarily study diagnostic processes and categories or people's illness experiences. Drawing on empirical studies that examine diagnosis and experiences of illness in varied settings (diagnosis during breast cancer surveillance, diagnosis and experience of autoimmune illness and incarcerated women's experiences of diagnoses and illness), in this article we build on our concept of regimes of patienthood to explain how diagnostic journeys, and the relations and power dynamics that manifest during this time, shape the illness experience and practices of patienthood. We construct a classification of diagnostic processes grounded in our empirical research that span (1) sudden diagnoses, (2) long, changing diagnostic journeys and (3) diagnostic journeys marked by disbelief and denial of care. Our findings demonstrate how diagnostic journeys and illness experiences are intertwined, with different diagnostic pathways impacting how illness is experienced. Analysing these categories collectively demonstrates that diagnostic journeys, while heterogenous, shape the practices that patients develop to manage health conditions and navigate unequal health-care encounters., (© 2023 The Authors. Sociology of Health & Illness published by John Wiley & Sons Ltd on behalf of Foundation for the Sociology of Health & Illness.)
- Published
- 2024
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8. Structural basis for binding of Drosophila Smaug to the GPCR Smoothened and to the germline inducer Oskar.
- Author
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Kubíková J, Ubartaitė G, Metz J, and Jeske M
- Subjects
- Animals, Humans, Germ Cells metabolism, Hedgehog Proteins genetics, Hedgehog Proteins metabolism, RNA, Messenger metabolism, Receptors, G-Protein-Coupled, Drosophila genetics, Drosophila Proteins genetics, Drosophila Proteins metabolism, RNA-Binding Proteins genetics, RNA-Binding Proteins metabolism, Repressor Proteins genetics, Repressor Proteins metabolism
- Abstract
Drosophila Smaug and its orthologs comprise a family of mRNA repressor proteins that exhibit various functions during animal development. Smaug proteins contain a characteristic RNA-binding sterile-α motif (SAM) domain and a conserved but uncharacterized N-terminal domain (NTD). Here, we resolved the crystal structure of the NTD of the human SAM domain-containing protein 4A (SAMD4A, a.k.a. Smaug1) to 1.6 Å resolution, which revealed its composition of a homodimerization D subdomain and a subdomain with similarity to a pseudo-HEAT-repeat analogous topology (PHAT) domain. Furthermore, we show that Drosophila Smaug directly interacts with the Drosophila germline inducer Oskar and with the Hedgehog signaling transducer Smoothened through its NTD. We determined the crystal structure of the NTD of Smaug in complex with a Smoothened α-helical peptide to 2.0 Å resolution. The peptide binds within a groove that is formed by both the D and PHAT subdomains. Structural modeling supported by experimental data suggested that an α-helix within the disordered region of Oskar binds to the NTD of Smaug in a mode similar to Smoothened. Together, our data uncover the NTD of Smaug as a peptide-binding domain.
- Published
- 2023
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9. RNA binding proteins Smaug and Cup induce CCR4-NOT-dependent deadenylation of the nanos mRNA in a reconstituted system.
- Author
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Pekovic F, Rammelt C, Kubíková J, Metz J, Jeske M, and Wahle E
- Subjects
- Animals, Humans, RNA, Messenger metabolism, RNA-Binding Proteins genetics, RNA-Binding Proteins metabolism, Drosophila genetics, Drosophila metabolism, Gene Expression Regulation, Ribonucleases genetics, Ribonucleases metabolism, Receptors, CCR4 genetics, Drosophila Proteins metabolism
- Abstract
Posttranscriptional regulation of the maternal nanos mRNA is essential for the development of the anterior - posterior axis of the Drosophila embryo. The nanos RNA is regulated by the protein Smaug, which binds to Smaug recognition elements (SREs) in the nanos 3'-UTR and nucleates the assembly of a larger repressor complex including the eIF4E-T paralog Cup and five additional proteins. The Smaug-dependent complex represses translation of nanos and induces its deadenylation by the CCR4-NOT deadenylase. Here we report an in vitro reconstitution of the Drosophila CCR4-NOT complex and Smaug-dependent deadenylation. We find that Smaug by itself is sufficient to cause deadenylation by the Drosophila or human CCR4-NOT complexes in an SRE-dependent manner. CCR4-NOT subunits NOT10 and NOT11 are dispensable, but the NOT module, consisting of NOT2, NOT3 and the C-terminal part of NOT1, is required. Smaug interacts with the C-terminal domain of NOT3. Both catalytic subunits of CCR4-NOT contribute to Smaug-dependent deadenylation. Whereas the CCR4-NOT complex itself acts distributively, Smaug induces a processive behavior. The cytoplasmic poly(A) binding protein (PABPC) has a minor inhibitory effect on Smaug-dependent deadenylation. Among the additional constituents of the Smaug-dependent repressor complex, Cup also facilitates CCR4-NOT-dependent deadenylation, both independently and in cooperation with Smaug., (© The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research.)
- Published
- 2023
- Full Text
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10. Community Engagement in Precision Medicine Research: Organizational Practices and Their Impacts for Equity.
- Author
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Shim JK, Foti N, Vasquez E, Fullerton SM, Bentz M, Jeske M, and Lee SS
- Subjects
- Humans, Precision Medicine, Community-Based Participatory Research, Data Collection, Community Participation, Biomedical Research
- Abstract
Background: In the wake of mandates for biomedical research to increase participation by members of historically underrepresented populations, community engagement (CE) has emerged as a key intervention to help achieve this goal., Methods: Using interviews, observations, and document analysis, we examine how stakeholders in precision medicine research understand and seek to put into practice ideas about who to engage, how engagement should be conducted, and what engagement is for., Results: We find that ad hoc, opportunistic, and instrumental approaches to CE exacted significant consequences for the time and resources devoted to engagement and the ultimate impacts it has on research. Critical differences emerged when engagement and research decisionmaking were integrated with each other versus occurring in parallel, separate parts of the study organization, and whether community members had the ability to determine which issues would be brought to them for consideration or to revise or even veto proposals made upstream based on criteria that mattered to them. CE was understood to have a range of purposes, from instrumentally facilitating recruitment and data collection, to advancing community priorities and concerns, to furthering long-term investments in relationships with and changes in communities. These choices about who to engage, what engagement activities to support, how to solicit and integrate community input into the workflow of the study, and what CE was for were often conditioned upon preexisting perceptions and upstream decisions about study goals, competing priorities, and resource availability., Conclusions: Upstream choices about CE and constraints of time and resources cascade into tradeoffs that often culminated in "pantomime community engagement." This approach can create downstream costs when engagement is experienced as improvised and sporadic. Transformations are needed for CE to be seen as a necessary scientific investment and part of the scientific process.
- Published
- 2023
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11. Rethinking Benefit and Responsibility in the Context of Diversity: Perspectives from the Front Lines of Precision Medicine Research.
- Author
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Vasquez EE, Foti N, McMahon CE, Jeske M, Bentz M, Fullerton S, Shim JK, and Lee SS
- Subjects
- Humans, Academies and Institutes, Precision Medicine, Ethics, Research
- Abstract
Introduction: Federal agencies have instituted guidelines to prioritize the enrollment and retention of diverse participants in precision medicine research (PMR). Prior studies examining participation of minoritized communities have shown that potential benefits represent a key determinant. Human subject research guidance, however, conceptualizes potential benefits narrowly, emphasizing generalized advances in medical knowledge. Further, few studies have provided qualitative data that critically examine how the concept of "benefit" is interpreted or challenged in the context of research practice. This paper examines the experiences of PMR investigators and frontline research staff to understand how standard approaches to benefit are received, contested, and negotiated "on the ground.", Methods: Findings are drawn from a qualitative project conducted across five US-based, federally funded PMR studies. Data collection included 125 in-depth interviews with a purposive sample of investigators, research staff, community advisory board members, and NIH program officers associated with these PMR studies., Results: Researchers report that the standard approach to benefit - which relies on the premise of altruism and the promise of incrementally advancing scientific knowledge - is frequently contested. Researchers experience moral distress over the unmet clinical, psychosocial, and material needs within the communities they are engaging. Many believe the broader research enterprise has a responsibility to better address these needs., Conclusion: Researchers frequently take issue with and sometimes negotiate what is owed to participants and to their communities in exchange for the data they provide. These experiences of moral distress and these improvisations warrant systematic redress, not by individual researchers but by the broader research ethics infrastructure., (© 2023 The Author(s). Published by S. Karger AG, Basel.)
- Published
- 2023
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12. Targeting Representation: Interpreting Calls for Diversity in Precision Medicine Research.
- Author
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Lee SS, Fullerton SM, McMahon CE, Bentz M, Saperstein A, Jeske M, Vasquez E, Foti N, Saco L, and Shim JK
- Subjects
- Humans, Biomedical Research, Precision Medicine
- Abstract
Scientists have identified a "diversity gap" in genetic samples and health data, which have been drawn predominantly from individuals of European ancestry, as posing an existential threat to the promise of precision medicine. Inadequate inclusion as articulated by scientists, policymakers, and ethicists has prompted large-scale initiatives aimed at recruiting populations historically underrepresented in biomedical research. Despite explicit calls to increase diversity, the meaning of diversity - which dimensions matter for what outcomes and why - remain strikingly imprecise. Drawing on our document review and qualitative data from observations and interviews of funders and research teams involved in five precision medicine research (PMR) projects, we note that calls for increasing diversity often focus on "representation" as the goal of recruitment. The language of representation is used flexibly to refer to two objectives: achieving sufficient genetic variation across populations and including historically disenfranchised groups in research. We argue that these dual understandings of representation are more than rhetorical slippage, but rather allow for the contemporary collection of samples and data from marginalized populations to stand in as correcting historical exclusion of social groups towards addressing health inequity. We trace the unresolved historical debates over how and to what extent researchers should procure diversity in PMR and how they contributed to ongoing uncertainty about what axes of diversity matter and why. We argue that ambiguity in the meaning of representation at the outset of a study contributes to a lack of clear conceptualization of diversity downstream throughout subsequent phases of the study., (Copyright ©2022, Yale Journal of Biology and Medicine.)
- Published
- 2022
13. Strategies of inclusion: The tradeoffs of pursuing "baked in" diversity through place-based recruitment.
- Author
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Shim JK, Bentz M, Vasquez E, Jeske M, Saperstein A, Fullerton SM, Foti N, McMahon C, and Lee SS
- Subjects
- Humans, Residence Characteristics, Biomedical Research, Research Personnel
- Abstract
US funding agencies have begun to institutionalize expectations that biomedical studies achieve defined thresholds for diversity among research participants, including in precision medicine research (PMR). In this paper, we examine how practices of recruitment have unfolded in the wake of these diversity mandates. We find that a very common approach to seeking diverse participants leverages understandings of spatial, geographic, and site diversity as proxies and access points for participant diversity. That is, PMR investigators recruit from a diverse sampling of geographic areas, neighborhoods, sites, and institutional settings as both opportunistic but also meaningful ways to "bake in" participant diversity. In this way, logics of geographic and institutional diversity shift the question from who to recruit, to where. However, despite seeing geographic and site diversity as social and scientific 'goods' in the abstract and as key to getting diverse participants, PMR teams told us that working with diverse sites was often difficult in practice due to constraints in funding, time, and personnel, and inadequate research infrastructures and capacity. Thus, the ways in which these geographic and institutional diversity strategies were implemented resulted ultimately in limiting the meaningful inclusion of populations and organizations that had not previously participated in biomedical research and reproduced the inclusion of institutions that are already represented. These prevailing assumptions about and practices of "baked-in" diversity in fact exacerbate and produce other forms of inequity, in research capacity and research representation. These findings underscore how structural inequities in research resources must be addressed for diversity to be achieved in both research sites and research participants., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)
- Published
- 2022
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14. Stability evaluation of morphine, hydromorphone, metamizole and esketamine containing analgesic mixtures applied for patient-controlled analgesia in hospice and palliative care.
- Author
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Harder M, Fiegl-Lechner A, Oberacher H, Horvath UEI, Schlager A, Jeske M, Kerndler S, Schüllner F, Bonn GK, and Rainer M
- Subjects
- Analgesia, Patient-Controlled, Analgesics, Opioid, Dipyrone, Humans, Ketamine, Morphine, Palliative Care methods, Hospices, Hydromorphone chemistry
- Abstract
In this study, different injection solutions containing opioid and nonopioid compounds used for patient-controlled analgesia in hospice and palliative care were evaluated in terms of analyte stability. Investigated injection solutions contained different combinations of morphine, hydromorphone, metamizole and esketamine. For the practical implementation, samples from infusion pumps were daily drawn over a period of 7 days at 22 and 37°C. Quantitative measurements were performed on a high-performance liquid chromatography system with ultraviolet detection applying a validated analytical method. All compounds apart from morphine showed no evident changes in concentration. However, a significant loss of morphine was observed for injection mixtures containing both morphine and metamizole at 37°C. After 7 days, only 72% of the initially measured morphine concentration was measured in the binary and 77% in the ternary mixture. Furthermore, an additional compound was detected that could represent the morphine-metamizole-adduct, "metamorphine". Based on these results, a significantly reduced morphine concentration must be expected after only 3 days if an injection solution mixture containing both morphine and metamizole is administered to a patient at 37°C. Since the analgesic effects of morphine-metamizole adducts have not yet been thoroughly investigated, further clinical studies are necessary before accurate conclusions can be drawn in this regard., (© 2022 The Authors. Biomedical Chromatography published by John Wiley & Sons Ltd.)
- Published
- 2022
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15. Beyond inclusion: Enacting team equity in precision medicine research.
- Author
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Jeske M, Vasquez E, Fullerton SM, Saperstein A, Bentz M, Foti N, Shim JK, and Lee SS
- Subjects
- Adolescent, Adult, Aged, Female, Genomics ethics, Health Workforce ethics, Humans, Laboratory Personnel organization & administration, Male, Middle Aged, Patient Care Team ethics, Patient Care Team organization & administration, United States, Young Adult, Biomedical Research ethics, Cultural Diversity, Laboratory Personnel ethics, Precision Medicine ethics
- Abstract
Purpose: To identify meanings of and challenges to enacting equitable diversification of genomics research, and specifically precision medicine research (PMR), teams., Methods: We conducted in-depth interviews with 102 individuals involved in three U.S.-based precision medicine research consortia and conducted over 400 observation hours of their working group meetings, consortium-wide meetings, and conference presentations. We also reviewed published reports on genomic workforce diversity (WFD), particularly those relevant to the PMR community., Results: Our study finds that many PMR teams encounter challenges as they strive to achieve equitable diversification on scientific teams. Interviewees articulated that underrepresented team members were often hired to increase the study's capacity to recruit diverse research participants, but are limited to on-the-ground staff positions with little influence over study design. We find existing hierarchies and power structures in the academic research ecosystem compound challenges for equitable diversification., Conclusion: Our results suggest that meaningful diversification of PMR teams will only be possible when team equity is prioritized as a core value in academic research communities., Competing Interests: The authors have declared that no competing interests exist.
- Published
- 2022
- Full Text
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