"What We're Doing Now Is More Than Water Cooler": Perspectives of Primary Care Leaders on Leading Through (and Beyond) COVID-19.

BACKGROUND: COVID-19 presented numerous challenges to primary care, but little formal research has explored the experience of practice leaders and their strategies for managing teams as the crisis unfolded. OBJECTIVE: Describe the experience of leaders in US primary care delivery organizations, and their strategies for leading teams during COVID-19 and beyond. DESIGN: Qualitative study using semi-structured interviews performed between 9/15/2020 and 8/31/2021. PARTICIPANTS: Purposive sample of 17 clinical leaders in a range of US primary care organizations. APPROACH: An iterative grounded review of interview transcripts was performed, followed by immersion/crystallization analysis. KEY RESULTS: Early in the pandemic, practice leaders reported facing rapid change and the need for constant decision-making, amidst an environment of stress, fear, and uncertainty, but this was buffered by a strong sense of purpose. Later, leaders noted the emergence of layered crises, and evolving challenges including fatigue, burnout, and strained relationships within their organizations and with the communities they serve. Leaders described four interrelated strategies for supporting their teams: (1) Being intentionally present, physically and emotionally; (2) Frequent and transparent communication; (3) Deepening and broadening relationships; (4) Increasing adaptive decision-making, alternating between formal hierarchical and flexible participatory processes. These strategies were influenced by individual leaders' perceived autonomy, which was impacted by the leader's specific role, and organizational size, complexity, and funding model. CONCLUSIONS: As the burnout and workforce crises have accelerated, the identified strategies can be useful to leaders to support teams and build organizational resilience in primary care moving forward.

Genome-wide discovery of somatic coding and noncoding mutations in pediatric endemic and sporadic Burkitt lymphoma.

Although generally curable with intensive chemotherapy in resource-rich settings, Burkitt lymphoma (BL) remains a deadly disease in older patients and in sub-Saharan Africa. Epstein-Barr virus (EBV) positivity is a feature in more than 90% of cases in malaria-endemic regions, and up to 30% elsewhere. However, the molecular features of BL have not been comprehensively evaluated when taking into account tumor EBV status or geographic origin. Through an integrative analysis of whole-genome and transcriptome data, we show a striking genome-wide increase in aberrant somatic hypermutation in EBV-positive tumors, supporting a link between EBV and activation-induced cytidine deaminase (AICDA) activity. In addition to identifying novel candidate BL genes such as SIN3A, USP7, and CHD8, we demonstrate that EBV-positive tumors had significantly fewer driver mutations, especially among genes with roles in apoptosis. We also found immunoglobulin variable region genes that were disproportionally used to encode clonal B-cell receptors (BCRs) in the tumors. These include IGHV4-34, known to produce autoreactive antibodies, and IGKV3-20, a feature described in other B-cell malignancies but not yet in BL. Our results suggest that tumor EBV status defines a specific BL phenotype irrespective of geographic origin, with particular molecular properties and distinct pathogenic mechanisms. The novel mutation patterns identified here imply rational use of DNA-damaging chemotherapy in some patients with BL and targeted agents such as the CDK4/6 inhibitor palbociclib in others, whereas the importance of BCR signaling in BL strengthens the potential benefit of inhibitors for PI3K, Syk, and Src family kinases among these patients.

Interprofessional education during the COVID-19 pandemic: finding the good in a bad situation.

COVID-19 restrictions necessitated wholescale conversion of curricula to online learning environments globally. We used a mixed-methods study design to evaluate the conversion of a large foundational interprofessional course, at our university, to an asynchronous online learning environment. A survey was used to gauge if students learned interprofessionally and about interprofessional collaborative practice (IPCP). A COVID-19 discussion board was used to assess learner knowledge of their own and other health professions and value for IPCP. Survey results indicated students perceived the online session as effective as it would have been in person. The COVID-19 discussion board presented evidence that students met all Interprofessional Education Collaborative core competencies for IPCP, shared knowledge of their and other health professions, and expressed the value and essentiality of IPCP. Findings support social context as a main requisite for interprofessional education, and within the context of the COVID-19 pandemic, students were able to heighten their connection to the global interprofessional community. Circumstances surrounding COVID-19 highlight the need for increasing IPCP education. One unforeseen positive that has emerged in spite of this global catastrophe is enhanced student awareness of IPCP and interprofessional comradery as evidenced through student discussions in this course.

Indigenizing Academics Through Leadership, Awareness, and Healing: The Impact of a Native American Health Seminar Series for Health Professionals, Students, and Community.

Health disparities have long affected American Indian and Alaska Native (AI/AN) populations. Transformations are needed in academia to help understand Indigenous 'ways of knowing.' Lifting the voices of AI/ANs in telling their stories could improve the education of students, faculty and the lay public. We collaborated to develop, implement and evaluate a Native American Health Seminar Series taught by AI/AN leaders on addressing health disparities among AI/AN people. A quasi-experimental mixed methods design included a 15-item survey to assess the impact of the Seminar Series on knowledge of AI/AN health issues and its influence, among students, on health career choices. During the 2018 academic year, three seminars were held and 243 participants attended. In total, 182 surveys (74.9%) were completed by faculty members, students and members of the lay public. Students (all categories combined) represented the highest participant group (48.4%), followed by the lay public at 30% and faculty at 21.6%. The highest scores on knowledge of Native health issues prior to seminar attendance were reported by those representing the lay public with a mean of 3.96 compared to 3.67 for faculty and 3.43 among students (p = 0.01), which was highly represented by Indigenous people. Increases in knowledge occurred in all participant groups. Among students, 65.6% initially indicated that they were not planning on pursuing a career in Native health. Among these, 56.9% indicated they were somewhat to extremely likely to pursue a career in Native health as a result of having attended the seminar.

Locomotor stimulant and discriminative stimulus effects of 'bath salt' cathinones.

A number of psychostimulant-like cathinone compounds are being sold as 'legal' alternatives to methamphetamine or cocaine. The purpose of these experiments was to determine whether cathinone compounds stimulate motor activity and have discriminative stimulus effects similar to those of cocaine and/or methamphetamine. 3,4-Methylenedioxypyrovalerone (MDPV), methylone, mephedrone, naphyrone, flephedrone, and butylone were tested for locomotor stimulant effects in mice and subsequently for substitution in rats trained to discriminate cocaine (10 mg/kg, intraperitoneally) or methamphetamine (1 mg/kg, intraperitoneally) from saline. All compounds fully substituted for the discriminative stimulus effects of cocaine and methamphetamine. Several commonly marketed cathinones produce discriminative stimulus effects comparable with those of cocaine and methamphetamine, which suggests that these compounds are likely to have similar abuse liabilities. MDPV and naphyrone produced locomotor stimulant effects that lasted much longer than those of cocaine or methamphetamine and therefore may be of particular concern, particularly because MDPV is one of the most commonly found substances associated with emergency room visits because of adverse effects of taking 'bath salts'.

Creating a Learning Plan for Prelicensure Students in Primary Care Clinical Experiences.

BACKGROUND: Registered nurses (RNs) working to the full scope of licensed practice can expand the capacity of the health care system and influence patient care quality. However, preparation of prelicensure nursing students to practice in primary care is particularly challenging due to curricular and practice site barriers. APPROACH: As part of a federally funded project to expand the primary care RN workforce, learning activities to teach key concepts of primary care nursing were designed and implemented. Students studied the concepts while placed in a primary care clinical setting and debriefed in a topical, instructor-facilitated, seminar. Current and best practices in primary care were explored, compared, and contrasted. OUTCOMES: Pre- and postsurveys revealed significant student learning related to selected primary care nursing concepts. Overall knowledge, skills, and attitudes increased significantly pre- to post-term. CONCLUSION: Concept-based learning activities can effectively support specialty nursing education in primary and ambulatory care settings.

An antidote to what's ailing healthcare workers: a new (old) way of relational leadership.

PURPOSE: The purpose of the study's mixed-methods evaluation was to examine the ways in which a relational leadership development intervention enhanced participants' abilities to apply relationship-oriented skills on their teams. DESIGN/METHODOLOGY/APPROACH: The authors evaluated five program cohorts from 2018-2021, involving 127 interprofessional participants. The study's convergent mixed-method approach analyzed post-course surveys for descriptive statistics and interpreted six-month post-course interviews using qualitative conventional content analysis. FINDINGS: All intervention features were rated as at least moderately impactful by at least 83% of participants. The sense of community, as well as psychological safety and trust created, were rated as impactful features of the course by at least 94% of participants. At six months post-intervention, participants identified benefits of greater self-awareness, deeper understanding of others and increased confidence in supporting others, building relationships and making positive changes on their teams. ORIGINALITY/VALUE: Relational leadership interventions may support participant skills for building connections, supporting others and optimizing teamwork. The high rate of skill application at six months post-course suggests that relational leadership development can be effective and sustainable in healthcare. As the COVID-19 pandemic and systemic crises continue to impact the psychological well-being of healthcare colleagues, relational leadership holds promise to address employee burnout, turnover and isolation on interprofessional care teams.

Enhancing American Indians'/Alaska Natives' Knowledge, Confidence, and Community During the Medical School Application Process: Findings From the Northwest Native American Center of Excellence.

PURPOSE: To describe a Medical School Applicant Workshop (MSAW); present lessons learned about its impact on American Indian/Alaska Native (AIAN) participants' knowledge, confidence, and sense of community; and report on participants' medical school application progress 1 year after workshop completion. METHOD: The Northwest Native American Center of Excellence at Oregon Health & Science University developed and implemented an annual 1-day AIAN MSAW in 2018. The main objectives of the workshop are for participants to gain insights into the medical school application process; learn strategies to competitively apply; receive feedback on their personal statement and mock interviews; and discuss the medical school application process with AIAN faculty, admissions deans, and peer-mentors. Recruitment of AIAN participants occurred via email; social media; text messaging; medical association contacts; and AIAN and science, technology, engineering, and mathematics organizations. Two surveys were administered: one immediately after and another 1-year after the workshop. RESULTS: Forty AIAN MSAW participants were accepted in 2018-2020. Findings indicate statistically significant increases in participants' self-reported knowledge of the medical school application process and in their self-reported confidence. Participants reported meeting other AIAN students was highly beneficial and feeling connected to a community of AIAN health professionals after attending the workshop. Among the 25 participants who completed the 1-year follow-up survey, 12 (48.0%) indicated applying to medical school; all 12 of these participants were invited to interview, and 11 were offered acceptance to at least one medical school. CONCLUSIONS: Completing the MSAW increased participants' knowledge, confidence, and sense of community. If other programs and institutions were to consider using the MSAW model to reduce barriers and provide supports specifically designed for AIANs before and during the medical school application process, medical schools may stand to further increase AIAN representation in the physician workforce and ultimately to decrease health inequities among AIANs.

Wy'east: An Innovative, Culturally Responsive Postbaccalaureate Pathway for American Indians and Alaska Natives.

PROBLEM: American Indians and Alaska Natives (AIANs) face significant health disparities that are exacerbated by limited access to high-quality, culturally congruent health care providers. There are no premedical postbaccalaureate programs focused on AIAN students. APPROACH: The Northwest Native American Center of Excellence designed the Wy'east Pathway in 2018 to increase the number of AIANs matriculating to U.S. medical schools by supporting those on the cusp of matriculation. Wy'east scholars undertake 10 months of structured programming to augment their academic preparation, improve their Medical College Admission Test (MCAT) scores, and enhance their confidence and cultural identity. Cultural events and mentorship opportunities with AIAN faculty, staff, and cultural liaisons are threaded throughout the pathway curriculum to foster cultural resilience, mentorship, and community. Scholars earn conditional acceptance to Oregon Health and Science University (OHSU) School of Medicine if they complete Wy'east and meet the following criteria: pass all examinations in the primary curricular threads, obtain a qualifying MCAT score, and meet professionalism standards. OUTCOMES: All 14 scholars who successfully completed Wy'east and met criteria in the first 2 cohorts (academic years 2018-2019 and 2019-2020) earned conditional acceptance to OHSU School of Medicine. Ten of the 14 scholars (71.4%) matriculated to OHSU School of Medicine, 2 (14.3%) matriculated to other medical schools, and 2 (14.3%) chose to pursue other health care fields. Wy'east scholars rated the foundational science of medicine and population health and epidemiology threads higher in terms of making them feel better prepared for medical school (mean = 4.71 and 4.83, respectively) than the academic skills and wellness thread (mean = 3.43). NEXT STEPS: Over the next 5 years, Wy'east will grow incrementally to offer a total of 18 conditional acceptance spots per cohort across 3 medical schools. Longitudinal tracking of Wy'east scholars' medical training and career outcomes will be conducted.

Carisoprodol-mediated modulation of GABAA receptors: in vitro and in vivo studies.

Carisoprodol is a frequently prescribed muscle relaxant. In recent years, this drug has been increasingly abused. The effects of carisoprodol have been attributed to its metabolite, meprobamate, a controlled substance that produces sedation via GABA(A) receptors (GABA(A)Rs). Given the structural similarities between carisoprodol and meprobamate, we used electrophysiological and behavioral approaches to investigate whether carisoprodol directly affects GABA(A)R function. In whole-cell patch-clamp studies, carisoprodol allosterically modulated and directly activated human alpha1beta2gamma2 GABA(A)R function in a barbiturate-like manner. At millimolar concentrations, inhibitory effects were apparent. Similar allosteric effects were not observed for homomeric rho1 GABA or glycine alpha1 receptors. In the absence of GABA, carisoprodol produced picrotoxin-sensitive, inward currents that were significantly larger than those produced by meprobamate, suggesting carisoprodol may directly produce GABAergic effects in vivo. When administered to mice via intraperitoneal or oral routes, carisoprodol elicited locomotor depression within 8 to 12 min after injection. Intraperitoneal administration of meprobamate depressed locomotor activity in the same time frame. In drug discrimination studies with carisoprodol-trained rats, the GABAergic ligands pentobarbital, chlordiazepoxide, and meprobamate each substituted for carisoprodol in a dose-dependent manner. In accordance with findings in vitro, the discriminative stimulus effects of carisoprodol were antagonized by a barbiturate antagonist, bemegride, but not by the benzodiazepine site antagonist, flumazenil. The results of our studies in vivo and in vitro collectively suggest the barbiturate-like effects of carisoprodol may not be due solely to its metabolite, meprobamate. Furthermore, the functional traits we have identified probably contribute to the abuse potential of carisoprodol.

Career Choice among First-Generation, Minority STEM College Students.

We qualitatively investigated ways in which undergraduates unpacked their perceptions of STEM careers after attending a seminar series that introduced them to diverse scientists. Using Social Cognitive Career Theory (SCCT) as a guiding framework, we explored how culturally-specific realities impacted students' career choices. Our findings suggest that familial ties and cultural expectations played key roles in determining how students navigated career choice. Our results have implications for how institutions navigate career pursuit discussions with students.

The Indigenous Faculty Forum: A Longitudinal Professional Development Program to Promote the Advancement of Indigenous Faculty in Academic Medicine.

American Indian, Alaska Native (AIAN) and Native Hawaiian and other Pacific Islander (NHPI) faculty, are substantially under-represented (<1%) at US medical schools. The Oregon Health & Science University's Northwest Native American Center of Excellence and The University of Hawai'i Native Hawaiian Center of Excellence have created an Indigenous Faculty Forum (IFF), a one-day structured course with flanking social activities, specifically designed to meet the unique needs of AIAN and NHPI academic faculty. It provided: (1) Indigenous space, (2) skill building, (3) networking, and (4) ongoing mentorship, each of which were included to specifically mitigate isolation and tokenism that negatively affects promotion and advancement. Two Forums have been conducted, first in Portland, OR in 2017 and the second in Hilo, Hawai'i in 2018. Nine of eighteen AIAN faculty in the three-state region (CA, OR, WA) attended IFF Session #1, representing 50% of known AIAN faculty in this region. Thirty-four Indigenous faculty from around the world attended IFF Session #2, with twenty-nine completing program evaluations. Respondents were predominantly female (81.6%), under age 44 (52.7%), and either instructors or assistant professors (52.6%). In terms of career choice, both sessions included primary care physicians as the most represented group (55.6% at Session #1 and 62.1% at Session #2). Increasing Indigenous faculty representation in US medical schools, while simultaneously fostering their career advancement and meaning in work, is vitally important. We have begun the work needed to address this problem and look forward to conducting more efforts, including longitudinal evaluation designs to study effectiveness.

Temporal and demographic variation in partial migration of the North Atlantic right whale.

Animal movement plays a fundamental role in the ecology of migratory species, and understanding migration patterns is required for effective management. To evaluate intrinsic and environmental factors associated with probabilities of endangered North Atlantic right whales Eubalaena glacialis migrating to a wintering ground off the southeastern United States (SEUS), we applied a multistate temporary emigration capture-recapture model to 22 years of photo-identification data. Migration probabilities for juveniles were generally higher yet more variable than those for adults, and non-calving adult females were the least likely group to migrate. The highest migration probabilities for juveniles and adult males coincided with years of relatively high calving rates, following years of higher prey availability in a fall feeding ground. Right whale migration to the SEUS can be classified as condition-dependent partial migration, which includes skipped breeding partial migration for reproductive females, and is likely influenced by tradeoffs among ecological factors such as reproductive costs and foraging opportunities that vary across individuals and time. The high variability in migration reported in this study provides insight into the ecological drivers of migration but presents challenges to right whale monitoring and conservation strategies.

On the Problem and Promise of Metaphor Use in Science and Science Communication.

The language of science is largely metaphorical. Scientists rely on metaphor and analogy to make sense of scientific phenomena and communicate their findings to each other and to the public. Yet, despite their utility, metaphors can also constrain scientific reasoning, contribute to public misunderstandings, and, at times, inadvertently reinforce stereotypes and messages that undermine the goals of inclusive science. This paper 1) examines the generative potential of metaphors to the advancement of scientific knowledge and science communication, 2) highlights the ways in which outdated metaphors may limit scientific inquiry and contribute to public misunderstandings, and 3) critically analyzes the implications of cryptic social and political messages embedded in common metaphors in the life sciences.

Increasing the efficiency of a targeted methicillin-resistant Staphylococcus aureus screening program.

An interdisciplinary team implemented a screening program targeting patients with a history of methicillin-resistant Staphylococcus aureus (MRSA), to reduce unnecessary contact isolation. After converting from a 2-step culture-based protocol to single polymerase chain reaction (PCR) testing, we increased the efficiency of the screening program from 77% to 100%. Despite the higher cost of PCR-based testing, this program remained cost-saving.

Clinical, patient experience and cost impacts of performing active surveillance on known methicillin-resistant Staphylococcus aureus positive patients admitted to medical-surgical units.

BACKGROUND: There is a large and growing body of evidence that methicillin-resistant Staphylococcus aureus (MRSA) screening programs are cost effective, but such screening represents a significant cost burden for hospitals. This study investigates the clinical, patient experience and cost impacts of performing active surveillance on known methicillin-resistant S aureus positive (MRSA+) patients admitted to 7 medical-surgical units of a large regional hospital, specifically to allow discontinuation of contact isolation. METHODS: We conducted mixed-methods retrospective evaluation of a process improvement project that screened admitted patients with known MRSA+ status for continued MRSA colonization. RESULTS: Of those eligible patients on our institution's MRSA+ list who did complete testing, 80.2% (130/162) were found to be no longer colonized, and only 19.8% (32/162) were still colonized. Forty-one percent (13/32) of interviewed patients in contact isolation for MRSA reported that isolation had affected their hospital stay, and 28% (9/32) of patients reported emotional distress resulting from their isolation. Total cost savings of the program are estimated at $101,230 per year across the 7 study units. CONCLUSION: Our findings provide supporting evidence that a screening program targeting patients with a history of MRSA who would otherwise be placed in isolation has the potential to improve outcomes and patient experience and reduce costs.

Winter habitat preferences for Florida manatees and vulnerability to cold.

To survive cold winter periods most, if not all, Florida manatees rely on warm-water refuges in the southern two-thirds of the Florida peninsula. Most refuges are either warm-water discharges from power plant and natural springs, or passive thermal basins that temporarily trap relatively warm water for a week or more. Strong fidelity to one or more refuges has created four relatively discrete Florida manatee subpopulations. Using statewide winter counts of manatees from 1999 to 2011, we provide the first attempt to quantify the proportion of animals using the three principal refuge types (power plants, springs, and passive thermal basins) statewide and for each subpopulation. Statewide across all years, 48.5% of all manatees were counted at power plant outfalls, 17.5% at natural springs, and 34.9 % at passive thermal basins or sites with no known warm-water features. Atlantic Coast and Southwest Florida subpopulations comprised 82.2% of all manatees counted (45.6% and 36.6%, respectively) with each subpopulation relying principally on power plants (66.6% and 47.4%, respectively). The upper St. Johns River and Northwest Florida subpopulations comprised 17.8% of all manatees counted with almost all animals relying entirely on springs (99.2% and 88.6% of those subpopulations, respectively). A record high count of 5,076 manatees in January 2010 revealed minimum sizes for the four subpopulations of: 230 manatees in the upper St. Johns River; 2,548 on the Atlantic Coast; 645 in Northwest Florida; and 1,774 in Southwest Florida. Based on a comparison of carcass recovery locations for 713 manatees killed by cold stress between 1999 and 2011 and the distribution of known refuges, it appears that springs offer manatees the best protection against cold stress. Long-term survival of Florida manatees will require improved efforts to enhance and protect manatee access to and use of warm-water springs as power plant outfalls are shut down.

Frequent alteration of the tumor suppressor gene APC in sporadic canine colorectal tumors.

Sporadic canine colorectal cancers (CRCs) should make excellent models for studying the corresponding human cancers. To molecularly characterize canine CRC, we investigated exonic sequence mutations of adenomatous polyposis coli (APC), the best known tumor suppressor gene of human CRC, in 23 sporadic canine colorectal tumors, including 8 adenomas and 15 adenocarcinomas, via exon-resequencing analysis. As a comparison, we also performed the same sequencing analysis on 10 other genes, either located at human 5q22 (the same locus as APC) or 18q21 (also frequently altered in human CRC), or known to play a role in human carcinogenesis. We noted that APC was the most significantly mutated gene in both canine adenomas and adenocarcinomas among the 11 genes examined. Significantly, we detected large deletions of ≥ 10 bases, many clustered near the mutation cluster region, as well as single or two base deletions in ~70% canine tumors of both subtypes. These observations indicate that like in the human, APC is also frequently altered in sporadic colorectal tumors in the dog and its alteration is an early event in canine colorectal tumorigenesis. Our study provides further evidence demonstrating the molecular similarity in pathogenesis between sporadic human and canine CRCs. This work, along with our previous copy number abnormality study, supports that sporadic canine CRCs are valid models of human CRCs at the molecular level.

A phase 2 trial of bevacizumab and high-dose interferon alpha 2B in metastatic melanoma.

Bevacizumab is a humanized recombinant monoclonal antibody that neutralizes vascular endothelial growth factor, an agent with proangiogenic effects in melanoma. Interferon alpha (IFN-α) has antiangiogenic properties through its ability to downregulate basic-fibroblast growth factor levels. We hypothesized that the coadministration of these agents would lead to tumor regression. Patients with metastatic melanoma received bevacizumab 15 mg/kg intravenously on day 1 of the 2-week cycle. IFN-α was administered thrice weekly at 5 MU/m subcutaneously during cycle 1 and was increased to 10 MU/m during cycle 2. Patients were restaged every 6 cycles. Patients with stable disease or a response continued with therapy. Baseline serum vascular endothelial growth factor and fibroblast growth factor were measured. Twenty-five patients were accrued. Mean age was 58.4 years. Eleven patients required IFN-α dose reductions due to toxicity. Common grade 3 toxicities associated with IFN-α included fatigue and myalgia. Bevacizumab administration was associated with grade 2-3 proteinuria in 6 patients. Grade 4 adverse events were pulmonary embolus (1), myocardial infarction (1), and stroke (1). Six patients had a partial response, and 5 patients exhibited stable disease that lasted more than 24 weeks (range: 30 to 122 wk). Median progression-free survival and overall survival were 4.8 and 17 months, respectively. Significantly lower fibroblast growth factor levels were observed in patients with a partial response compared to those with stable or progressive disease (P=0.040). Administration of bevacizumab with IFN led to a clinical response in 24% of patients with stage IV melanoma and stabilization of disease in another 20% of patients. This regimen has activity in advanced melanoma.