Detection of chromosomal aneuploidy in ancient genomes.

Ancient DNA is a valuable tool for investigating genetic and evolutionary history that can also provide detailed profiles of the lives of ancient individuals. In this study, we develop a generalised computational approach to detect aneuploidies (atypical autosomal and sex chromosome karyotypes) in the ancient genetic record and distinguish such karyotypes from contamination. We confirm that aneuploidies can be detected even in low-coverage genomes ( ~ 0.0001-fold), common in ancient DNA. We apply this method to ancient skeletal remains from Britain to document the first instance of mosaic Turner syndrome (45,X0/46,XX) in the ancient genetic record in an Iron Age individual sequenced to average 9-fold coverage, the earliest known incidence of an individual with a 47,XYY karyotype from the Early Medieval period, as well as individuals with Klinefelter (47,XXY) and Down syndrome (47,XY, + 21). Overall, our approach provides an accessible and automated framework allowing for the detection of individuals with aneuploidies, which extends previous binary approaches. This tool can facilitate the interpretation of burial context and living conditions, as well as elucidate past perceptions of biological sex and people with diverse biological traits.

Does Sponsorship Promote Equity in Career Advancement in Academic Medicine? A Scoping Review.

Sponsorship describes a set of actions wherein an influential champion (sponsor) uses their position to actively support a colleague's career by helping them gain visibility, recognition, and/or positions. There is growing awareness of the importance of sponsorship for career advancement in academic medicine, particularly for women and those who are historically underrepresented and excluded in medicine (UIM). This scoping review examines the current landscape of evidence, and knowledge gaps, on sponsorship as it relates to career advancement in academic medicine for women and UIM faculty. We searched peer-reviewed literature in PubMed, Embase, and Web of Science (WoS) over the past 50 years (from 1973 through July 2023). Sixteen studies were included in the final review. We found relative consensus on sponsorship definition and value to career advancement. Heterogeneity in study design limited our ability to directly compare study outcomes. All included studies focused on gender differences in sponsorship: two of four quantitative studies found men were more likely to receive sponsorship, one reported no gender differences, and one was insufficiently powered. All but one of the qualitative studies reported gender differences, with women less likely to access or be identified for sponsorship. The mixed-methods studies suggested sponsorship may vary by career stage. Only two studies analyzed sponsorship for UIM populations. The existing data are inconclusive regarding best ways to measure and assess sponsorship, what institutional support (e.g., structured programs, formal recognition, or incentives for sponsorship) should look like, and at what career stage sponsorship is most important. Addressing this knowledge gap will be critically important for understanding what sponsorship best practices, if any, should be used to promote equity in career advancement in academic medicine. We advocate for commitment at the institutional and national levels to develop new infrastructure for transparently and equitably supporting women and UIM in career advancement.

An individual with Sarmatian-related ancestry in Roman Britain.

In the second century CE the Roman Empire had increasing contact with Sarmatians, nomadic Iranian speakers occupying an area stretching from the Pontic-Caspian steppe to the Carpathian mountains, both in the Caucasus and in the Danubian borders of the empire.1,2,3 In 175 CE, following their defeat in the Marcomannic Wars, emperor Marcus Aurelius drafted Sarmatian cavalry into Roman legions and deployed 5,500 Sarmatian soldiers to Britain, as recorded by contemporary historian Cassius Dio.4,5 Little is known about where the Sarmatian cavalry were stationed, and no individuals connected with this historically attested event have been identified to date, leaving its impact on Britain largely unknown. Here we document Caucasus- and Sarmatian-related ancestry in the whole genome of a Roman-period individual (126-228 calibrated [cal.] CE)-an outlier without traceable ancestry related to local populations in Britain-recovered from a farmstead site in present-day Cambridgeshire, UK. Stable isotopes support a life history of mobility during childhood. Although several scenarios are possible, the historical deployment of Sarmatians to Britain provides a parsimonious explanation for this individual's extraordinary life history. Regardless of the factors behind his migrations, these results highlight how long-range mobility facilitated by the Roman Empire impacted provincial locations outside of urban centers.

Language-Concordant Care: a Qualitative Study Examining Implementation of Physician Non-English Language Proficiency Assessment.

BACKGROUND: Language concordance can increase access to care for patients with language barriers and improve patient health outcomes. However, systematically assessing and tracking physician non-English language skills remains uncommon in most health systems. This is a missed opportunity for health systems to maximize language-concordant care. OBJECTIVE: To determine barriers and facilitators to participation in non-English language proficiency assessment among primary care physicians. DESIGN: Qualitative, semi-structured interviews. PARTICIPANTS: Eleven fully and partially bilingual primary care physicians from a large academic health system with a language certification program (using a clinician oral proficiency interview). APPROACH: Interviews aimed to identify barriers and facilitators to participation in non-English language assessment. Two researchers independently and iteratively coded transcripts using a thematic analysis approach with constant comparison to identify themes. KEY RESULTS: Most participants were women (N= 9; 82%). Participants reported proficiency in Cantonese, Mandarin, Russian, and Spanish. All fully bilingual participants (n=5) had passed the language assessment; of the partially bilingual participants (n=6), four did not test, one passed with marginal proficiency, and one did not pass. Three themes emerged as barriers to assessment participation: (1) beliefs about the negative consequences (emotional and material) of not passing the test, (2) time constraints and competing demands, and (3) challenging test format and structure. Four themes emerged as facilitators to increase assessment adoption: (1) messaging consistent with professional ethos, (2) organizational culture that incentivizes certification, (3) personal empowerment about language proficiency, and (4) individuals championing certification. CONCLUSIONS: To increase language assessment participation and thus ensure quality language-concordant care, health systems must address the identified barriers physicians experience and leverage potential facilitators. Findings can inform health system interventions to standardize the requirements and process, increase transparency, provide resources for preparation and remediation, utilize messaging focused on patient care quality and safety, and incentivize participation.

Faculty knowledge, actions, and perceptions of sponsorship: an institutional survey study.

BACKGROUND: Women and underrepresented in medicine and the health sciences (URiM) faculty face inequities in advancement. Career sponsorship may be a remedy. Few studies have described sponsorship in academic medicine and none across an institution. OBJECTIVE: To examine faculty awareness, experiences, and perceptions of sponsorship at a large academic health center. DESIGN: Anonymous online survey. PARTICIPANTS: Faculty with a ≥50% appointment. MAIN MEASURES: The survey contained 31 Likert, multiple-choice, yes/no, and open-ended questions about familiarity with the concept of sponsorship; experience of having or being a sponsor; receipt of specific sponsorship activities; sponsorship impact and satisfaction; mentorship and sponsorship co-occurrence; and perception of inequities. Open-ended questions were analyzed using content analysis. KEY RESULTS: Thirty-one percent of the surveyed faculty (903/2900) responded of whom 53% (477/903) were women and 10% (95/903) were URiM. Familiarity with sponsorship was higher among assistant (91%, 269/894) and associate (182/894; 64%) professors versus full professors (38%, 329/894); women (67%, 319/488) versus men (62%, 169/488); and URiM (77%, 66/517) versus non-URiM faculty (55%, 451/517). A majority had a personal sponsor (528/691; 76%) during their career and were satisfied with their sponsorship (64%, 532/828). However, when responses from faculty of different professorial ranks were stratified by gender and URiM identity, we observed possible cohort effects. Furthermore, 55% (398/718) of respondents perceived that women received less sponsorship than men and 46% (312/672) that URiM faculty received less than their peers. We identified seven qualitative themes: sponsorship importance, growing awareness and change, institutional biases and deficiencies, groups getting less sponsorship, people with sponsorship power, conflation with mentorship, and potential for negative impact. CONCLUSIONS: A majority of respondents at a large academic health center reported sponsorship familiarity, receipt, and satisfaction. Yet many perceived persistent institutional biases and the need for systematic change to improve sponsorship transparency, equity, and impact.

Yersinia pestis genomes reveal plague in Britain 4000 years ago.

Extinct lineages of Yersinia pestis, the causative agent of the plague, have been identified in several individuals from Eurasia between 5000 and 2500 years before present (BP). One of these, termed the 'LNBA lineage' (Late Neolithic and Bronze Age), has been suggested to have spread into Europe with human groups expanding from the Eurasian steppe. Here, we show that the LNBA plague was spread to Europe's northwestern periphery by sequencing three Yersinia pestis genomes from Britain, all dating to ~4000 cal BP. Two individuals were from an unusual mass burial context in Charterhouse Warren, Somerset, and one individual was from a single burial under a ring cairn monument in Levens, Cumbria. To our knowledge, this represents the earliest evidence of LNBA plague in Britain documented to date. All three British Yersinia pestis genomes belong to a sublineage previously observed in Bronze Age individuals from Central Europe that had lost the putative virulence factor yapC. This sublineage is later found in Eastern Asia ~3200 cal BP. While the severity of the disease is currently unclear, the wide geographic distribution within a few centuries suggests substantial transmissibility.

"Long Overdue": Nurse and Resident Physician Perspectives on Implementation of Dual-Handset Interpreter Phones in the Inpatient Setting.

Background: Patients with language barriers suffer significant health disparities, including adverse events and poor health outcomes. While remote language services can help improve language access, these modalities remain persistently underused. The objective of this study was to understand clinician experiences and challenges using dual-handset interpreter telephones and to inform recommendations for future language access interventions. Methods: We conducted four focus groups with nurses (N=14) and resident physicians (N=20) to understand attitudes toward dual-handset interpreter telephones in the hospital, including general impressions, effects on communication, situations in which they did and did not use them, and impact on clinical care. Three researchers independently coded all transcripts using a constant comparative approach, meeting repeatedly to discuss coding and to reconcile differences to reach consensus. Results: We identified five salient themes, including increased language access (improved convenience, flexibility, and versatility of phones over in-person or ad hoc interpreters); effects on interpersonal processes of care (improved ability to communicate directly with patients); effects on clinical processes of care (improvements in critical patient care functions, including pain and medication management); impact on time (needing extra time for interpreted encounters and perceived delays impacting future use); and patients for whom, and circumstances in which, the dual-handset interpreter telephone is inadequate (e.g., complex discussions, hands-on instruction, or multiple speakers are present). Conclusions: Our findings indicate that clinicians value dual-handset interpretation in bridging communication barriers and highlight recommendations to guide future implementation interventions to increase the uptake of remote language services in hospital settings.

Comprehensive Assessment of Clinical Learning Environments to Drive Improvement: Lessons Learned from a Pilot Program.

Problem: Recognition of the importance of clinical learning environments (CLEs) in health professions education has led to calls to evaluate and improve the quality of such learning environments. As CLEs sit at the crossroads of education and healthcare delivery, leadership from both entities should share the responsibility and accountability for this work. Current data collection about the experience and outcomes for learners, faculty, staff, and patients tends to occur in fragmented and siloed ways, and available tools to assess clinical learning environments are limited in scope. In addition, from an organizational perspective oversight of education and patient care is often done by separate entities, and not infrequently is there a sense of competing interests. Intervention: We aimed to design and pilot a holistic approach to assessment and review of CLEs and establish whether such a formative assessment process could be used to engage stakeholders from education, departmental, and health systems leadership in improvement of CLEs. Utilizing concepts of implementation science, we planned and executed a holistic assessment process for CLEs, monitored the impact of the assessment, and reflected on the process. We focused the assessment on four pillars characterizing exemplary learning environments: 1) Environment is inclusive, promotes diversity and collaboration; 2) Focus on continuous quality improvement; 3) Alignment between work and learning; and 4) Integration of education and healthcare mission. Context: At our institution, medical trainees rotate through several different health systems, but clinical and educational leadership converge at the departmental level. We therefore focused this proof-of-concept project on two large clinical departments at our institution, centering on medical learners from undergraduate and graduate medical education. For each department, a small team of champions helped create an assessment grid based on the four pillars and identified existing quantitative evaluation data sources. Champions subsequently collected qualitative data through observations, focus groups, and interviews to fill any gaps in available quantitative data. Impact: The project teams shared reports summarizing findings and recommendations with departmental, clinical, and educational leadership. Subsequent meetings with these stakeholders led to actionable plans for improvement as well as sustained structures for collaborative work between the different stakeholder groups. Lessons Learned: This project demonstrated the feasibility and effectiveness of collating, analyzing, and sharing data from various sources in engaging different stakeholder groups to initiate actionable improvement plans. Collating quantitative data from existing resources was a powerful way to demonstrate common issues in CLEs, and qualitative data provided further detail to inform improvement initiatives. Other institutions can adapt this approach to guide assessment and quality improvement of CLEs. As a next step, we are creating a comprehensive learning environment scorecard to allow for comparison of clinical learning environment quality across institutions and over time.

Assessing Medical Student Readiness to Navigate Language Barriers in Telehealth: Cross-sectional Survey Study.

BACKGROUND: The COVID-19 pandemic has greatly increased telehealth usage in the United States. Patients with limited English proficiency (LEP) face barriers to health care, which may be mitigated when providers work with professional interpreters. However, telehealth may exacerbate disparities if clinicians are not trained to work with interpreters in that setting. Although medical students are now involved in telehealth on an unprecedented scale, no educational innovations have been published that focus on digital care across language barriers. OBJECTIVE: The aim of this study is to investigate advanced medical students' confidence in caring for patients with LEP during telehealth encounters. METHODS: We administered a written survey to medical students on clinical clerkships at one US institution in August and September 2020. We assessed students' overall confidence in working with interpreters; confidence in performing 8 clinical tasks during in-person versus telehealth encounters; and frequency of performing 5 different clinical tasks with patients with LEP compared to English-speaking patients during in-person versus telehealth encounters. Wilcoxon signed-rank tests and chi-square tests were used to compare confidence and task performance frequency, respectively, for patients with LEP versus English-speaking patients during telehealth encounters. Students were also asked to identify barriers to care for patients with LEP. The free-response questions were qualitatively analyzed using open coding to identify key themes. RESULTS: Of 300 medical students surveyed, 121 responded. Furthermore, 72 students answered >50% of questions and were included in the analyses. Compared to caring for patients with LEP during in-person encounters, respondents were less confident in working with interpreters (P<.001), developing trust (P<.001), identifying agenda (P=.005), eliciting preferences for diabetes management (P=.01), and empowering patients in lifestyle modifications (P=.04) during telehealth encounters. During both in-person and telehealth encounters, approximately half of students (40%-78%) reported engaging less frequently in every clinical task with patients with LEP and this was as low as 22% (13/59) for some tasks. Students identified these key barriers to care for patients with LEP: time pressure, interpretation quality and access, technical difficulties, cultural differences, and difficulty with rapport building. CONCLUSIONS: Advanced medical students were significantly less confident caring for patients with LEP via telehealth than in person. Broader implementation of training around navigating language barriers is necessary for telehealth care, which has rapidly expanded in the United States. Our study identified potential key areas for curricular focus, including creating patient-centered agendas and management plans within the constraints of virtual settings. These developments must take place simultaneously with systems-level improvements in interpreter infrastructure to ensure high-quality care for linguistically diverse patients.

Transitioning from intravenous to subcutaneous insulin in the medical intensive care unit.

BACKGROUND: There is a paucity of studies on transitions from IV insulin infusion (IVII) to subcutaneous (SC) insulin in the medical ICU (MICU). METHODS: We conducted a retrospective study of patients admitted to the Cleveland Clinic MICU from June 2013 to January 2014 who received IVII. We compared blood glucose (BG) control between 3 cohorts based on timing of basal insulin dose: (1) NB (no basal), (2) IB (incorrect basal), (3) CB (correct basal) at 5 time points post-IVII discontinuation (1, 4, 8, 12, and 24h). Insulin doses used for transitioning were compared with 80% of estimated 24h IVII total. Analysis was done using chi-square, ANOVA and t-tests. RESULTS: There were 269 patients (NB 166, IB 45, CB 58), 55% male with a mean age 58±16years. 103 patients (38%) had a transition attempted (IB 21%, CB 17%). The NB cohort had better BG than the IB cohort at all time points (p<0.001) but also lower HbA1c, prior DM diagnosis and home insulin use (p<0.001). IB and CB did not have significantly different BG with mean BG>180mg/dL at 4/5 time intervals. However, the dose of basal insulin used was less than 80% of estimated 24h IVII total (IB 21.4 vs 49.6U, CB 25vs 57.1U). Despite this, 15% of patients in the IB cohort and 24% of patients in the CB had hypoglycemic events. CONCLUSION: The low rates of IV to SC insulin transitions raises the question of challenges to transitions.

Type 2 diabetes and osteoarthritis: a systematic review and meta-analysis.

BACKGROUND: Observational studies have reported an association between type 2 diabetes and osteoarthritis (OA) development and progression. However no systematic review of the literature exists assessing whether this association is consistently true. We aimed to systematically review the association between type 2 diabetes and the presence, development, and progression of OA. METHODS: We searched MEDLINE, SCOPUS, EMBASE, the Web of Science, and Grey Literature (through August 2014) for prospective cohort, cross-sectional, and case-control studies with confidence intervals (CI) that reported an association between type 2 diabetes and impaired glucose tolerance (IGT) and the development or presence of OA of any joint. RESULTS: Ten studies and fourteen ratios were included in the analysis. The pooled population size in our meta-regression was 16,742 patients. Type 2 diabetes was significantly associated with the development or presence of OA (OR; 1·21, 95% CI: 1·02-1·41). In the subset of 7 studies that did control for weight or BMI there was an increased odds of OA associated with type 2 diabetes was (OR: 1·25, 95% CI: 1·05-1·46) from a smaller pool of patients (n=7156). CONCLUSIONS: Type 2 diabetes is associated with the development and presence of radiographic and symptomatic OA even when controlling for body mass index and weight.

BRD4 short isoform interacts with RRP1B, SIPA1 and components of the LINC complex at the inner face of the nuclear membrane.

Recent studies suggest that BET inhibitors are effective anti-cancer therapeutics. Here we show that BET inhibitors are effective against murine primary mammary tumors, but not pulmonary metastases. BRD4, a target of BET inhibitors, encodes two isoforms with opposite effects on tumor progression. To gain insights into why BET inhibition was ineffective against metastases the pro-metastatic short isoform of BRD4 was characterized using mass spectrometry and cellular fractionation. Our data show that the pro-metastatic short isoform interacts with the LINC complex and the metastasis-associated proteins RRP1B and SIPA1 at the inner face of the nuclear membrane. Furthermore, histone binding arrays revealed that the short isoform has a broader acetylated histone binding pattern relative to the long isoform. These differential biochemical and nuclear localization properties revealed in our study provide novel insights into the opposing roles of BRD4 isoforms in metastatic breast cancer progression.

Membranes, minerals, and proteins of developing vertebrate enamel.

Developing tooth enamel is formed as organized mineral in a specialized protein matrix. In order to analyze patterns of enamel mineralization and enamel protein expression in species representative of the main extant vertebrate lineages, we investigated developing teeth in a chondrichthyan, the horn shark, a teleost, the guppy, a urodele amphibian, the Mexican axolotl, an anuran amphibian, the leopard frog, two lepidosauria, a gecko and an iguana, and two mammals, a marsupial, the South American short-tailed gray opossum, and the house mouse. Electron microscopic analysis documented the presence of a distinct basal lamina in all species investigated. Subsequent stages of enamel biomineralization featured highly organized long and parallel enamel crystals in mammals, lepidosaurians, the frog, and the shark, while amorphous mineral deposits and/or randomly oriented crystals were observed in the guppy and the axolotl. In situ hybridization using a full-length mouse probe for amelogenin mRNA resulted in amelogenin specific signals in mouse, opossum, gecko, frog, axolotl, and shark. Using immunohistochemistry, amelogenin and tuftelin enamel proteins were detected in the enamel organ of many species investigated, but tuftelin epitopes were also found in other tissues. The anti-M179 antibody, however, did not react with the guppy and axolotl enameloid matrix. We conclude that basic features of vertebrate enamel/enameloid formation such as the presence of enamel proteins or the mineral deposition along the dentin-enamel junction were highly conserved in vertebrates. There were also differences in terms of enamel protein distribution and mineral organization between the vertebrates lineages. Our findings indicated a correlation between the presence of amelogenins and the presence of long and parallel hydroxyapatite crystals in tetrapods and shark.