Gene flow from Fraxinus cultivars into natural stands of Fraxinus pennsylvanica occurs range-wide, is regionally extensive, and is associated with a loss of allele richness.

In North America, a comparatively small number of Fraxinus (ash) cultivars were planted in large numbers in both urban and rural environments across the entire range of Fraxinus pennsylvanica Marsh (green ash) over the last 80 years. Undetected cultivar gene flow, if extensive, could significantly lower genetic diversity within populations, suppress differentiation between populations, generate interspecific admixture not driven by long-standing natural processes, and affect the impact of abiotic and biotic threats. In this investigation we generated the first range-wide genetic assessment of F. pennsylvanica to detect the extent of cultivar gene flow into natural stands. We used 16 EST-SSR markers to genotype 48 naturally regenerated populations of F. pennsylvanica distributed across the native range (1291 trees), 19 F. pennsylvanica cultivars, and one F. americana L. (white ash) cultivar to detect cultivar propagule dispersal into these populations. We detected first generation cultivar parentage with high confidence in 171 individuals in 34 of the 48 populations and extensive cultivar parentage (23-50%) in eight populations. The incidence of cultivar parentage was negatively associated with allele richness (R2 = 0.151, p = 0.006). The evidence for a locally high frequency of cultivar propagule dispersal and the interspecific admixture in eastern populations will inform Fraxinus gene pool conservation strategies and guide the selection of individuals for breeding programs focused on increasing resistance to the emerald ash borer (Agrilus planipennis Fairmaire), an existential threat to the Fraxinus species of North America.

Viloxazine Increases Extracellular Concentrations of Norepinephrine, Dopamine, and Serotonin in the Rat Prefrontal Cortex at Doses Relevant for the Treatment of Attention-Deficit/Hyperactivity Disorder.

Background: Viloxazine ER (viloxazine extended-release capsules; Qelbree®), a nonstimulant attention-deficit/hyperactivity disorder (ADHD) treatment, has known activity as a norepinephrine (NE) transporter (NET) inhibitor. In vitro studies have also shown direct pharmacological effects on specific serotonin (5-HT) receptors, but not on the serotonin transporter (SERT). An in vivo microdialysis study in rats showed viloxazine (50 mg/kg i.p.) increased extracellular 5-HT, NE, and dopamine (DA) in the prefrontal cortex (PFC), a key brain region in ADHD pathology. This study evaluated whether these effects occur at clinically relevant concentrations. Methods: Microdialysis experiments were conducted in freely-moving, Sprague-Dawley rats (males, 8 weeks). Viloxazine (1, 3, 10, 30 mg/kg) was administered intraperitoneally to establish the dose range in rats at which viloxazine plasma concentrations aligned with those of individuals with ADHD administered therapeutic doses of viloxazine ER. Concentrations of unbound viloxazine, NE, 5-HT, DA, and NE and 5-HT metabolites (3,5-dihydroxyphenylglycol [DHPG] and 5-hydroxyindoleacetic acid [5-HIAA]) were measured in PFC interstitial fluid. After identifying a therapeutically relevant dose (30 mg/kg), the experiment was repeated using 30 and 50 mg/kg viloxazine (as 50 mg/kg increased NE, 5-HT, and DA in prior studies). Results: Viloxazine unbound (free drug) plasma concentrations in rats at 30 mg/kg were comparable to free drug concentrations in individuals with ADHD taking clinically effective doses (based on validated population PK models). Viloxazine 30 mg/kg significantly increased extracellular NE, 5-HT, and DA PFC levels compared to vehicle. Concomitant decreases in DHPG, but not 5-HIAA, support the inhibitory effect of viloxazine on NET but not SERT. Conclusion: At clinically relevant concentrations, viloxazine increases PFC NE, DA, and 5-HT. Prefrontal augmentation of 5-HT does not appear to result from 5-HT reuptake inhibition but may be related to activation of 5-HT neurons. The potential therapeutic role of serotonergic effects in ADHD treatment merits further exploration.

Analysis of narrative assessments of internal medicine resident performance: are there differences associated with gender or race and ethnicity?

BACKGROUND: Equitable assessment is critical in competency-based medical education. This study explores differences in key characteristics of qualitative assessments (i.e., narrative comments or assessment feedback) of internal medicine postgraduate resident performance associated with gender and race and ethnicity. METHODS: Analysis of narrative comments included in faculty assessments of resident performance from six internal medicine residency programs was conducted. Content analysis was used to assess two key characteristics of comments- valence (overall positive or negative orientation) and specificity (detailed nature and actionability of comment) - via a blinded, multi-analyst approach. Differences in comment valence and specificity with gender and race and ethnicity were assessed using multilevel regression, controlling for multiple covariates including quantitative competency ratings. RESULTS: Data included 3,383 evaluations with narrative comments by 597 faculty of 698 residents, including 45% of comments about women residents and 13.2% about residents who identified with race and ethnicities underrepresented in medicine. Most comments were moderately specific and positive. Comments about women residents were more positive (estimate 0.06, p 0.045) but less specific (estimate - 0.07, p 0.002) compared to men. Women residents were more likely to receive non-specific, weakly specific or no comments (adjusted OR 1.29, p 0.012) and less likely to receive highly specific comments (adjusted OR 0.71, p 0.003) or comments with specific examples of things done well or areas for growth (adjusted OR 0.74, p 0.003) than men. Gendered differences in comment specificity and valence were most notable early in training. Comment specificity and valence did not differ with resident race and ethnicity (specificity: estimate 0.03, p 0.32; valence: estimate - 0.05, p 0.26) or faculty gender (specificity: estimate 0.06, p 0.15; valence: estimate 0.02 p 0.54). CONCLUSION: There were significant differences in the specificity and valence of qualitative assessments associated with resident gender with women receiving more praising but less specific and actionable comments. This suggests a lost opportunity for well-rounded assessment feedback to the disadvantage of women.

Exploring gender and thematic differences in qualitative assessments of internal medicine resident performance.

INTRODUCTION: Evidence suggests gender disparities in medical education assessment, including differences in ratings of competency and narrative comments provided in resident performance assessments. This study explores how gender manifests within the content of qualitative assessments (i.e., narrative comments or performance feedback) of resident performance. METHODS: Qualitative content analysis was used to explore gender-based differences in narrative comments included in faculty assessments of resident performance during inpatient medicine rotations at six Internal Medicine residency programs, 2016-2017. A blinded, multi-analyst approach was employed to identify themes across comments. Patterns in themes with resident gender and post-graduate year (PGY) were explored, focusing on PGY2 and PGY3 when residents are serving in the team leader role. RESULTS: Data included 3,383 evaluations with narrative comments of 385 men (55.2%) and 313 women residents (44.8%). There were thematic differences in narrative comments received by men and women residents and how these themes manifested within comments changed with training time. Compared to men, comments about women had a persistent relationship-orientation and emphasized confidence over training including as interns and in PGY2 and PGY3, when serving as team leader. The relationship-orientation was characterized not only by the residents' communal attributes but also their interpersonal and communication skills, including efforts supporting others and establishing the tone for the team. Comments about women residents often highlighted confidence, including recommendations around behaviors that convey confidence in decision-making and team leadership. DISCUSSION: There were gender-based thematic differences in qualitative assessments. Comments about women resident team leaders highlight relationship building skills and urge confidence and actions that convey confidence as team leader. Persistent attention to communal skills suggests gendered expectations for women resident team leaders and a lost opportunity for well-rounded feedback to the disadvantage of women residents. These findings may inform interventions to promote equitable assessment, such as providing feedback across the competencies.

A quantum engine in the BEC-BCS crossover.

Heat engines convert thermal energy into mechanical work both in the classical and quantum regimes1. However, quantum theory offers genuine non-classical forms of energy, different from heat, which so far have not been exploited in cyclic engines. Here we experimentally realize a quantum many-body engine fuelled by the energy difference between fermionic and bosonic ensembles of ultracold particles that follows from the Pauli exclusion principle2. We employ a harmonically trapped superfluid gas of 6Li atoms close to a magnetic Feshbach resonance3 that allows us to effectively change the quantum statistics from Bose-Einstein to Fermi-Dirac, by tuning the gas between a Bose-Einstein condensate of bosonic molecules and a unitary Fermi gas (and back) through a magnetic field4-10. The quantum nature of such a Pauli engine is revealed by contrasting it with an engine in the classical thermal regime and with a purely interaction-driven device. We obtain a work output of several 106 vibrational quanta per cycle with an efficiency of up to 25%. Our findings establish quantum statistics as a useful thermodynamic resource for work production.

Functional Impairments Associated With ADHD in Adulthood and the Impact of Pharmacological Treatment.

OBJECTIVE: Among untreated adults, functional impairments associated with ADHD are widespread and cumulative, and can include social, educational, and professional impairments, increased risk of accidents and mortality, and reduced quality of life. Here, we review the most prominent functional impairments in adults with ADHD and summarize evidence describing the potential role of medication in improving outcomes. METHOD: Articles related to the search terms "ADHD," "adult," and functional impairments were identified through Google Scholar and PubMed and selected for inclusion based on four criteria: strength of evidence, relevance to current challenges in adult ADHD, impact on the field, and recency of the results. RESULTS: We identified 179 papers to support the conclusions on the relationship between ADHD and functional impairments, and the impact of pharmacological therapy on functional impairments. CONCLUSION: This narrative review provides evidence that pharmacological treatment can be effective in minimizing not only the symptoms of ADHD, but its functional consequences as well.

A simulation-enhanced, spaced learning, interprofessional "code blue" curriculum improves ACLS algorithm adherence and trainee resuscitation skill confidence.

In-hospital cardiac arrest resuscitation training often happens in silos, with minimal interprofessional training. The aim of this study was to implement and evaluate a simulation-enhanced, interprofessional cardiac arrest curriculum in a university hospital. The curriculum ran monthly for 12 months, training interprofessional teams of internal medicine residents, nurses, respiratory therapists, and pharmacy residents. Teams participated in a 90-min high-fidelity simulation including "code blue" (30 min) followed by a 30-min debriefing and a repeat identical simulated "code blue" scenario. Teams were tested in an unannounced mock Code Blue the following month. Advanced Cardiac Life Support (ACLS) algorithm adherence was assessed using a standardized checklist. In-hospital cardiac arrest (IHCA) incidence and survival was tracked for 2 years prior, during, and 1 year after curriculum implementation. Team ACLS-algorithm adherence at baseline varied from 47% to 90% (mean of 71 ± 11%) and improved immediately following training (mean 88 ± 4%, range 80-93%, p = .011). This improvement persisted but decreased in magnitude over 1 month (mean 81 ± 7%, p = .013). Medical resident self-reported comfort levels with resuscitation skills varied widely at baseline, but improved for all skills post-curriculum. This simulation-enhanced, spaced practice, interprofessional curriculum resulted in a sustained improvement in team ACLS algorithm adherence.

In-Vivo Evaluation of a Reinforced Ovine Biologic for Plastic and Reconstructive Procedures in a Non-human Primate Model of Soft Tissue Repair.

Background: Biologic matrices are used in plastic and reconstructive surgical procedures to aid in the kinetics of soft tissue repair and promote functional tissue formation. The human acellular dermal matrix AlloDerm is widely used; however, it is offered at a relatively high cost, and its dermal composition may not provide an ideal remodeling scaffold. OviTex Plastic and Reconstructive Surgery (PRS) Resorbable and Permanent are reinforced biologic matrices engineered with layers of ovine forestomach matrix embroidered with small amounts of polymer to optimize biophysical performance. This study compared the healing outcomes of these matrices in a non-human primate model of soft tissue repair. Methods: Animals were implanted with test articles in surgically created full-thickness midline abdominal wall defects and evaluated macroscopically and histologically at 2, 4, 12, and 24 weeks. Results: Both OviTex PRS Permanent and Resorbable matrices exhibited earlier host cell infiltration, neovascularization, and collagen deposition and also fully remodeled into the host tissue by 12 weeks post implantation. AlloDerm had less host cell infiltration and neovascularization at early time points and never fully integrated into the surrounding host tissue. There was no statistical difference in overall inflammation between AlloDerm and either OviTex PRS product at any time point, despite small amounts of polymer reinforcement in OviTex products. Conclusions: In a primate soft tissue repair model, OviTex PRS Permanent and Resorbable matrices performed comparably with the leading human acellular dermal matrix. OviTex PRS Permanent and Resorbable are less expensive than alternatives like AlloDerm and may promote faster host cell proliferation and functional remodeling in some soft tissue repair applications.

Ultracold Bose Gases in Dynamic Disorder with Tunable Correlation Time.

We study experimentally the dissipative dynamics of ultracold bosonic gases in a dynamic disorder potential with tunable correlation time. First, we measure the heating rate of thermal clouds exposed to the dynamic potential and present a model of the heating process, revealing the microscopic origin of dissipation from a thermal, trapped cloud of bosons. Second, for Bose-Einstein condensates, we measure the particle loss rate induced by the dynamic environment. Depending on the correlation time, the losses are either dominated by heating of residual thermal particles or the creation of excitations in the superfluid, a notion we substantiate with a rate model. Our results illuminate the interplay between superfluidity and time-dependent disorder and on more general grounds establish ultracold atoms as a platform for studying spatiotemporal noise and time-dependent disorder.

Association of Gender and Race/Ethnicity with Internal Medicine In-Training Examination Performance in Graduate Medical Education.

BACKGROUND: Disparities in objective assessments in graduate medical education such as the In-Training Examination (ITE) that disadvantage women and those self-identifying with race/ethnicities underrepresented in medicine (URiM) are of concern. OBJECTIVE: Examine ITE trends longitudinally across post-graduate year (PGY) with gender and race/ethnicity. DESIGN: Longitudinal analysis of resident ITE metrics at 7 internal medicine residency programs, 2014-2019. ITE trends across PGY of women and URiM residents compared to non-URiM men assessed via ANOVA. Those with ITE scores associated with less than 90% probability of passing the American Board of Internal Medicine certification exam (ABIM-CE) were identified and odds of being identified as at-risk between groups were assessed with chi square. PARTICIPANTS: A total of 689 IM residents, including 330 women and URiM residents (48%). MAIN MEASURES: ITE score KEY RESULTS: There was a significant difference in ITE score across PGY for women and URiM residents compared to non-URiM men (F(2, 1321) 4.46, p=0.011). Adjusting for program, calendar year, and baseline ITE, women and URiM residents had smaller ITE score gains (adjusted mean change in score between PGY1 and PGY3 (se), non-URiM men 13.1 (0.25) vs women and URiM residents 11.4 (0.28), p<0.001). Women and URiM residents had greater odds of being at potential risk for not passing the ABIM-CE (OR 1.75, 95% CI 1.10 to 2.78) with greatest odds in PGY3 (OR 3.13, 95% CI 1.54 to 6.37). CONCLUSION: Differences in ITE over training were associated with resident gender and race/ethnicity. Women and URiM residents had smaller ITE score gains across PGY translating into greater odds of potentially being seen as at-risk for not passing the ABIM-CE. Differences in ITE over training may reflect differences in experiences of women and URiM residents during training and may lead to further disparities.

Association Between Resident Race and Ethnicity and Clinical Performance Assessment Scores in Graduate Medical Education.

PURPOSE: To assess the association between internal medicine (IM) residents' race/ethnicity and clinical performance assessments. METHOD: The authors conducted a cross-sectional analysis of clinical performance assessment scores at 6 U.S. IM residency programs from 2016 to 2017. Residents underrepresented in medicine (URiM) were identified using self-reported race/ethnicity. Standardized scores were calculated for Accreditation Council for Graduate Medical Education core competencies. Cross-classified mixed-effects regression assessed the association between race/ethnicity and competency scores, adjusting for rotation time of year and setting; resident gender, postgraduate year, and IM In-Training Examination percentile rank; and faculty gender, rank, and specialty. RESULTS: Data included 3,600 evaluations by 605 faculty of 703 residents, including 94 (13.4%) URiM residents. Resident race/ethnicity was associated with competency scores, with lower scores for URiM residents (difference in adjusted standardized scores between URiM and non-URiM residents, mean [standard error]) in medical knowledge (-0.123 [0.05], P = .021), systems-based practice (-0.179 [0.05], P = .005), practice-based learning and improvement (-0.112 [0.05], P = .032), professionalism (-0.116 [0.06], P = .036), and interpersonal and communication skills (-0.113 [0.06], P = .044). Translating this to a 1 to 5 scale in 0.5 increments, URiM resident ratings were 0.07 to 0.12 points lower than non-URiM resident ratings in these 5 competencies. The interaction with faculty gender was notable in professionalism (difference between URiM and non-URiM for men faculty -0.199 [0.06] vs women faculty -0.014 [0.07], P = .01) with men more than women faculty rating URiM residents lower than non-URiM residents. Using the 1 to 5 scale, men faculty rated URiM residents 0.13 points lower than non-URiM residents in professionalism. CONCLUSIONS: Resident race/ethnicity was associated with assessment scores to the disadvantage of URiM residents. This may reflect bias in faculty assessment, effects of a noninclusive learning environment, or structural inequities in assessment.

Application of somatic embryogenesis for development of emerald ash borer-resistant white ash and green ash varietals.

Emerald ash borer (Agrilus planipennis; EAB) has devastated populations of ash (Fraxinus spp.) trees in dozens of U.S. states and Canada over the past few decades. The continued survival of scattered ash trees known as "lingering ash" in heavily infested natural stands, however, offers evidence of genetic resistance or tolerance to EAB. These surviving or "lingering" ash individuals may form the basis for reforestation programs in EAB-impacted areas, and clonal mass-propagation of these genotypes can help accelerate these efforts. Between 2013 and 2018, we initiated embryogenic cultures by culturing immature zygotic embryos from open-pollinated (OP) seeds collected from several surviving white ash and green ash trees in Michigan and Pennsylvania. In addition, in 2018, we initiated cultures from crosses made between lingering green ash parents from the USDA Forest Service ash breeding program in Ohio. Somatic embryos were produced by growing cultures in liquid suspension, followed by fractionation and plating on semisolid medium to produce developmentally synchronous populations of somatic embryos. Somatic embryo germination and conversion were enhanced by a combination of pre-germination cold treatment and inclusion of activated charcoal and gibberellic acid in the germination medium. Ash somatic seedlings derived from OP explants grew rapidly following transfer to potting mix and somatic seedlings representing nine ash clones were acclimatized, grown in the greenhouse and planted in a preliminary field test, along with EAB-resistant Manchurian ash (F. mandshurica) and EAB-susceptible control seedlings. Somatic seedlings have now been produced from cultures that originated from seeds derived from the progeny of lingering green ash parents and an ex vitro germination protocol has shown some promise for accelerating early somatic seedling growth. Results of this research could provide the basis for scaled-up production of EAB-resistant ash varieties for seed orchard production for forest restoration and cultivar development for urban tree restoration.

Observing the loss and revival of long-range phase coherence through disorder quenches.

Relaxation of quantum systems is a central problem in nonequilibrium physics. In contrast to classical systems, the underlying quantum dynamics results not only from atomic interactions but also from the long-range coherence of the many-body wave function. Experimentally, nonequilibrium states of quantum fluids are usually created using moving objects or laser potentials, directly perturbing and detecting the system's density. However, the fate of long-range phase coherence for hydrodynamic motion of disordered quantum systems is less explored, especially in three dimensions. Here, we unravel how the density and phase coherence of a Bose-Einstein condensate of 6Li2 molecules respond upon quenching on or off an optical speckle potential. We find that, as the disorder is switched on, long-range phase coherence breaks down one order of magnitude faster than the density of the quantum gas responds. After removing it, the system needs two orders of magnitude longer times to reestablish quantum coherence, compared to the density response. We compare our results with numerical simulations of the Gross-Pitaevskii equation on large three-dimensional grids, finding an overall good agreement. Our results shed light on the importance of long-range coherence and possibly long-lived phase excitations for the relaxation of nonequilibrium quantum many-body systems.

A high-quality reference genome for Fraxinus pennsylvanica for ash species restoration and research.

Green ash (Fraxinus pennsylvanica) is the most widely distributed ash tree in North America. Once common, it has experienced high mortality from the non-native invasive emerald ash borer (EAB; Agrilus planipennis). A small percentage of native green ash trees that remain healthy in long-infested areas, termed "lingering ash," display partial resistance to the insect, indicating that breeding and propagating populations with higher resistance to EAB may be possible. To assist in ash breeding, ecology and evolution studies, we report the first chromosome-level assembly from the genus Fraxinus for F. pennsylvanica with over 99% of bases anchored to 23 haploid chromosomes, spanning 757 Mb in total, composed of 49.43% repetitive DNA, and containing 35,470 high-confidence gene models assigned to 22,976 Asterid orthogroups. We also present results of range-wide genetic variation studies, the identification of candidate genes for important traits including potential EAB-resistance genes, and an investigation of comparative genome organization among Asterids based on this reference genome platform. Residual duplicated regions within the genome probably resulting from a recent whole genome duplication event in Oleaceae were visualized in relation to wild olive (Olea europaea var. sylvestris). We used our F. pennsylvanica chromosome assembly to construct reference-guided assemblies of 27 previously sequenced Fraxinus taxa, including F. excelsior. Thus, we present a significant step forward in genomic resources for research and protection of Fraxinus species.

Morc1 as a potential new target gene in mood regulation: when and where to find in the brain.

Recent animal and human studies connected the Morc family CW-type zinc finger 1 (Morc1) gene with early life stress and depression. Moreover, the Morc superfamily is related to epigenetic regulation in diverse nuclear processes. So far, the Morc1 gene was mainly studied in spermatogenesis, whereas its distribution and function in the brain are still unknown. In a first attempt to characterize Morc1 in the brain, we performed a Western Blot analysis as well as a real-time PCR analysis during different stages of development. Additionally, we detected Morc1 mRNA using real-time PCR in different mood-regulating brain areas in adult rats. We found that MORC1 protein as well as Morc1 mRNA is already expressed in the brain at embryonic day 14 and is stably expressed until adulthood. Furthermore, Morc1 mRNA is present in many important brain areas of mood regulation like the medial prefrontal cortex, the nucleus accumbens, the hippocampus, the hypothalamus, and the amygdala. The ample distribution in the brain and its molecular structure as a zinc finger protein indicate that Morc1 might act as a transcription factor. This function and its expression in mood-regulating areas already in the early brain development turn Morc1 into a possible candidate gene for mediating early life stress and depression.

A Rare Case of Escherichia coli Chest Wall Abscess With Rib Osteomyelitis in a Patient With Crohn's Disease.

Primary chest wall abscess due to hematogenous spread is very rare and has seldom been documented in the literature, with most reported cases attributed to Mycobacterium tuberculosis. Prompt diagnosis and management with antibiotics, and evacuation of the abscess, is imperative as the infection can lead to systemic or disseminated infection, including erosion into surrounding bone if left untreated. We describe the case of a 67-year-old female with severe Crohn's disease receiving anti-tumor necrosis factor-alpha (TNF-α) therapy, Etanercept presenting with localized Escherichia coli (E. coli) chest wall abscess with erosion into the surrounding rib. This case highlights a rare clinical entity, chest wall abscess, which is also an unusual site of E. coli infection. Only three previous cases of E. coli primary chest wall abscess can be found in the published literature. This case also highlights a possible association of severe Crohn's disease predisposing to complicated soft tissue infection.

Gender Representation Matters: Intervention to Solicit Medical Resident Input to Enable Equity in Leadership in Graduate Medical Education.

PROBLEM: Gender equity in leadership across academic medicine remains a concern. The case of chief resident (CR) offers an opportunity to explore novel strategies in leadership selection in graduate medical education (GME). Means of identifying potential candidates for CR often rely on faculty assessment of resident performance, yet implicit gender bias has the potential to influence this assessment. APPROACH: To diversify the metrics used in CR selection, an intervention was implemented to solicit resident input to identify candidates for CR at 2 U.S. internal medicine residency programs in 2018 and 2019. This involved a simple, cross-sectional survey of residents in which they were asked to identify individual residents as good candidates for consideration for CR. OUTCOMES: There were 298 of 518 internal medicine resident responses to this intervention across sites and years (mean 58.2% response rate). Nomination patterns of residents and program leaders correlated significantly (correlation coefficient 0.62, P < .001). Controlling for site and year, gender was a significant factor associated with who residents nominated for CR (ß-coefficient 0.325, P = .004) with women residents more likely to identify women for CR (odds ratio 1.38, 95% confidence interval 1.11-1.73). Fifty residents nominated themselves for CR, and there was no significant difference by gender (ß-coefficient 0.038, P = .91). NEXT STEPS: Soliciting resident input to identify candidates for CR may enable gender representation of candidates for this position. Influencing candidate choices may be a promising way to impact leadership selection in medicine.