Absence of YhdP, TamB, and YdbH leads to defects in glycerophospholipid transport and cell morphology in Gram-negative bacteria.

The outer membrane (OM) of Gram-negative bacteria provides the cell with a formidable barrier that excludes external threats. The two major constituents of this asymmetric barrier are lipopolysaccharide (LPS) found in the outer leaflet, and glycerophospholipids (GPLs) in the inner leaflet. Maintaining the asymmetric nature and balance of LPS to GPLs in the OM is critical for bacterial viability. The biosynthetic pathways of LPS and GPLs are well characterized, but unlike LPS transport, how GPLs are translocated to the OM remains enigmatic. Understanding this aspect of cell envelope biology could provide a foundation for new antibacterial therapies. Here, we report that YhdP and its homologues, TamB and YdbH, members of the "AsmA-like" family, are critical for OM integrity and necessary for proper GPL transport to the OM. The absence of the two largest AsmA-like proteins (YhdP and TamB) leads to cell lysis and antibiotic sensitivity, phenotypes that are rescued by reducing LPS synthesis. We also find that yhdP, tamB double mutants shed excess LPS through outer membrane vesicles, presumably to maintain OM homeostasis when normal anterograde GPL transport is disrupted. Moreover, a yhdP, tamB, ydbH triple mutant is synthetically lethal, but if GPL transport is partially restored by overexpression of YhdP, the cell shape adjusts to accommodate increased membrane content as the cell accumulates GPLs in the IM. Our results therefore suggest a model in which "AsmA-like" proteins transport GPLs to the OM, and when hindered, changes in cell shape and shedding of excess LPS aids in maintaining OM asymmetry.

Anterior quadratus lumborum catheters for elective cesarean section: A double-blind, randomized, placebo-controlled trial.

BACKGROUND: Optimizing pain management following cesarean section is crucial for the well-being of both mother and infant. Various types of quadratus lumborum blocks have exhibited reduced opioid consumption and pain scores after cesarean section. However, duration of block effect is relatively short. The aim of this study was to investigate the analgesic efficacy of the anterior quadratus lumborum catheters for cesarean section. METHODS: All 32 enrolled participants were allocated to postoperative bilateral ultrasound-guided anterior quadratus lumborum catheter placement with injection of 60 mL ropivacaine 0.375% after cesarean section. Randomization at 2 h resulted in either 60 mL ropivacaine 0.2% or 60 mL isotonic saline injected through the catheters, with subsequent 22-h infusion of either ropivacaine 0.2% or isotonic saline with an infusion rate of 4 mL h-1 per catheter. Participants in the active group received a total of 697 mg ropivacaine during the first 24 h. All participants received the standard postoperative multimodal pain regimen, and a final bilateral injection at 24-h post-catheter placement of 60 mL ropivacaine 0.375% in total. The primary outcome was time to first opioid administration. Secondary outcomes were pain scores, time to first ambulation, nausea and vomiting, accumulated opioid consumption, and catheter displacement rates. RESULTS: No significant intergroup differences were observed following the randomized intervention. Median time to first opioid (IQR) was (active vs. placebo) 414 (283, 597) vs. 428 (245, 552) minutes, with a median difference (CI) of -14 (-184 to 262) min, p = .32. CONCLUSION: Bilateral anterior quadratus lumborum catheters with continuous infusion did not prolong time to first opioid after elective cesarean section.

Modal and amodal cognition: an overarching principle in various domains of psychology.

Accounting for how the human mind represents the internal and external world is a crucial feature of many theories of human cognition. Central to this question is the distinction between modal as opposed to amodal representational formats. It has often been assumed that one but not both of these two types of representations underlie processing in specific domains of cognition (e.g., perception, mental imagery, and language). However, in this paper, we suggest that both formats play a major role in most cognitive domains. We believe that a comprehensive theory of cognition requires a solid understanding of these representational formats and their functional roles within and across different domains of cognition, the developmental trajectory of these representational formats, and their role in dysfunctional behavior. Here we sketch such an overarching perspective that brings together research from diverse subdisciplines of psychology on modal and amodal representational formats so as to unravel their functional principles and their interactions.

Cardiolipin aids in lipopolysaccharide transport to the gram-negative outer membrane.

In Escherichia coli, cardiolipin (CL) is the least abundant of the three major glycerophospholipids in the gram-negative cell envelope. However, E. coli harbors three distinct enzymes that synthesize CL: ClsA, ClsB, and ClsC. This redundancy suggests that CL is essential for bacterial fitness, yet CL-deficient bacteria are viable. Although multiple CL-protein interactions have been identified, the role of CL still remains unclear. To identify genes that impact fitness in the absence of CL, we analyzed high-density transposon (Tn) mutant libraries in combinatorial CL synthase mutant backgrounds. We found LpxM, which is the last enzyme in lipid A biosynthesis, the membrane anchor of lipopolysaccharide (LPS), to be critical for viability in the absence of clsA Here, we demonstrate that CL produced by ClsA enhances LPS transport. Suppressors of clsA and lpxM essentiality were identified in msbA, a gene that encodes the indispensable LPS ABC transporter. Depletion of ClsA in ∆lpxM mutants increased accumulation of LPS in the inner membrane, demonstrating that the synthetic lethal phenotype arises from improper LPS transport. Additionally, overexpression of ClsA alleviated ΔlpxM defects associated with impaired outer membrane asymmetry. Mutations that lower LPS levels, such as a YejM truncation or alteration in the fatty acid pool, were sufficient in overcoming the synthetically lethal ΔclsA ΔlpxM phenotype. Our results support a model in which CL aids in the transportation of LPS, a unique glycolipid, and adds to the growing repertoire of CL-protein interactions important for bacterial transport systems.

A novel type of colistin resistance genes selected from random sequence space.

Antibiotic resistance is a rapidly increasing medical problem that severely limits the success of antibiotic treatments, and the identification of resistance determinants is key for surveillance and control of resistance dissemination. Horizontal transfer is the dominant mechanism for spread of resistance genes between bacteria but little is known about the original emergence of resistance genes. Here, we examined experimentally if random sequences can generate novel antibiotic resistance determinants de novo. By utilizing highly diverse expression libraries encoding random sequences to select for open reading frames that confer resistance to the last-resort antibiotic colistin in Escherichia coli, six de novo colistin resistance conferring peptides (Dcr) were identified. The peptides act via direct interactions with the sensor kinase PmrB (also termed BasS in E. coli), causing an activation of the PmrAB two-component system (TCS), modification of the lipid A domain of lipopolysaccharide and subsequent colistin resistance. This kinase-activation was extended to other TCS by generation of chimeric sensor kinases. Our results demonstrate that peptides with novel activities mediated via specific peptide-protein interactions in the transmembrane domain of a sensory transducer can be selected de novo, suggesting that the origination of such peptides from non-coding regions is conceivable. In addition, we identified a novel class of resistance determinants for a key antibiotic that is used as a last resort treatment for several significant pathogens. The high-level resistance provided at low expression levels, absence of significant growth defects and the functionality of Dcr peptides across different genera suggest that this class of peptides could potentially evolve as bona fide resistance determinants in natura.

Direct Determination of the Rate of Intersystem Crossing in a Near-IR Luminescent Cr(III) Triazolyl Complex.

A detailed understanding of the dynamics of photoinduced processes occurring in the electronic excited state is essential in informing the rational design of photoactive transition-metal complexes. Here, the rate of intersystem crossing in a Cr(III)-centered spin-flip emitter is directly determined through the use of ultrafast broadband fluorescence upconversion spectroscopy (FLUPS). In this contribution, we combine 1,2,3-triazole-based ligands with a Cr(III) center and report the solution-stable complex [Cr(btmp)2]3+ (btmp = 2,6-bis(4-phenyl-1,2,3-triazol-1-yl-methyl)pyridine) (13+), which displays near-infrared (NIR) luminescence at 760 nm (τ = 13.7 µs, ϕ = 0.1%) in fluid solution. The excited-state properties of 13+ are probed in detail through a combination of ultrafast transient absorption (TA) and femtosecond-to-picosecond FLUPS. Although TA spectroscopy allows us to observe the evolution of phosphorescent excited states within the doublet manifold, more significantly and for the first time for a complex of Cr(III), we utilize FLUPS to capture the short-lived fluorescence from initially populated quartet excited states immediately prior to the intersystem crossing process. The decay of fluorescence from the low-lying 4MC state therefore allows us to assign a value of (823 fs)-1 to the rate of intersystem crossing. Importantly, the sensitivity of FLUPS to only luminescent states allows us to disentangle the rate of intersystem crossing from other closely associated excited-state events, something which has not been possible in the spectroscopic studies previously reported for luminescent Cr(III) systems.

Discontinuous Galerkin integral equation method for light scattering from complex nanoparticle assemblies.

This paper presents a discontinuous Galerkin (DG) integral equation (IE) method for the electromagnetic analysis of arbitrarily-shaped plasmonic assemblies. The use of nonconformal meshes provides improved flexibility for CAD prototyping and tessellation of the input geometry. The formulation can readily address nonconformal multi-material junctions (where three or more material regions meet), allowing to set very different mesh sizes depending on the material properties of the different subsystems. It also enables the use of h-refinement techniques to improve accuracy without burdening the computational cost. The continuity of the equivalent electric and magnetic surface currents across the junction contours is enforced by a combination of boundary conditions and local, weakly imposed, interior penalties within the junction regions. A comprehensive study is made to compare the performance of different IE-DG alternatives applied to plasmonics. The numerical experiments conducted validate the accuracy and versatility of this formulation for the resolution of complex nanoparticle assemblies.

Ultrafast electronic, infrared, and X-ray absorption spectroscopy study of Cu(I) phosphine diimine complexes.

The study aims to understand the role of the transient bonding in the interplay between the structural and electronic changes in heteroleptic Cu(I) diimine diphosphine complexes. This is an emerging class of photosensitisers which absorb in the red region of the spectrum, whilst retaining a sufficiently long excited state lifetime. Here, the dynamics of these complexes are explored by transient absorption (TA) and time-resolved infrared (TRIR) spectroscopy, which reveal ultrafast intersystem crossing and structural distortion occurring. Two potential mechanisms affecting excited state decay in these complexes involve a transient formation of a solvent adduct, made possible by the opening up of the Cu coordination centre in the excited state due to structural distortion, and by a transient coordination of the O-atom of the phosphine ligand to the copper center. X-ray absorption studies of the ground electronic state have been conducted as a prerequisite for the upcoming X-ray spectroscopy studies which will directly determine structural dynamics. The potential for these complexes to be used in bimolecular applications is confirmed by a significant yield of singlet oxygen production.

Deterministic nanoscale quantum spin-defect implantation and diffraction strain imaging.

Local crystallographic features negatively affect quantum spin defects by changing the local electrostatic environment, often resulting in degraded or varied qubit optical and coherence properties. Few tools exist that enable the deterministic synthesis and study of such intricate systems on the nano-scale, making defect-to-defect strain environment quantification difficult. In this paper, we highlight state-of-the-art capabilities from the U.S. Department of Energy's Nanoscale Science Research Centers that directly address these shortcomings. Specifically, we demonstrate how complementary capabilities of nano-implantation and nano-diffraction can be used to demonstrate the quantum relevant, spatially deterministic creation of neutral divacancy centers in 4H silicon carbide, while investigating and characterizing these systems on the≤25nmscale with strain sensitivities on the order of1×10-6,relevant to defect formation dynamics. This work lays the foundation for ongoing studies into the dynamics and deterministic formation of low strain homogeneous quantum relevant spin defects in the solid state.

The intertransverse process block single- or multiple-injection? A study protocol.

BACKGROUND AND AIMS: Intertransverse process (ITP) blocks are applied on the posterior side of the thoracic paravertebral space. The modality is described as being a paravertebral block by proxy, possibly providing a similar analgesic effect as the thoracic paravertebral block. However, systematic evidence on anaesthetised dermatomes and the extent of cutaneous sensory loss following ITP blocks is sparse. This study aims to test the single- versus the multiple-injection ITP block. The primary outcome is the number of anaesthetised thoracic dermatomes for each block type. METHODS: Twelve healthy male volunteers will participate in this randomised, procedure-related, double-blinded, non-inferiority crossover trial after informed consent. Blinded participants will receive either a unilateral single-injection ITP block with 21 mL ropivacaine 7.5 mg/mL including two sham blocks or a unilateral multiple-injection ITP block with 3 × 7 mL ropivacaine 7.5 mg/mL on study Day 1, and the other modality on study Day 2. Block applicants will be blinded from outcome assessment and vice versa. Following block application sensory test by mechanical pinprick and temperature discrimination will be performed. Anterior truncal thermography will be measured three times after block application to compare skin temperature in the mid-clavicular line between the blocked and the contralateral non-blocked hemithorax. In addition, blood pressure changes are measured three times non-invasively. DISCUSSION: The current study will provide substantial knowledge regarding the cutaneous sensory loss of the ITP block. Furthermore, the study might provide insight regarding the possible clinical usage of thermography as a reliable instrument for measuring nerve block efficacy.

The fundamentals of Artificial Intelligence in medical education research: AMEE Guide No. 156.

The use of Artificial Intelligence (AI) in medical education has the potential to facilitate complicated tasks and improve efficiency. For example, AI could help automate assessment of written responses, or provide feedback on medical image interpretations with excellent reliability. While applications of AI in learning, instruction, and assessment are growing, further exploration is still required. There exist few conceptual or methodological guides for medical educators wishing to evaluate or engage in AI research. In this guide, we aim to: 1) describe practical considerations involved in reading and conducting studies in medical education using AI, 2) define basic terminology and 3) identify which medical education problems and data are ideally-suited for using AI.

Unconscious Influences on "Free Will" Movement Initiation: Slow-wave Brain Stimulation and the Readiness Potential.

A central objective in the study of volition has been to identify how changes in neural activity relate to voluntary-"free will"-movement. The readiness potential (RP) is observed in the EEG as a slow-building signal that precedes action onset. Many consider the RP as a marker of an underlying preparatory process for initiating voluntary movement. However, the RP may emerge from ongoing slow-wave brain oscillations that influence the timing of movement initiation in a phase-dependent manner. Transcranial alternating current stimulation (tACS) enables brain oscillations to be entrained at the frequency of stimulation. We delivered tACS at a slow-wave frequency over frontocentral motor areas while participants (n = 30) performed a simple, self-paced button press task. During the active tACS condition, participants showed a tendency to initiate actions in the phase of the tACS cycle that corresponded to increased negative potentials across the frontocentral motor region. Comparisons of premovement EEG activity observed over frontocentral and central scalp electrodes showed earlier onset and increased amplitude of RPs from active stimulation compared with sham stimulation. This suggests that movement-related activity in the brain can be modulated by the delivery of weak, nonconsciously perceptible alternating currents over frontocentral motor regions. We present novel findings that support existing theories, which suggest the timing of voluntary movement is influenced by the phase of slow-changing oscillating brain states.

Motor training is improved by concurrent application of slow oscillating transcranial alternating current stimulation to motor cortex.

Physical exercise and neurorehabilitation involve repetitive training that can induce changes in motor performance arising from neuroplasticity. Retention of these motor changes occurs via an encoding process, during which rapid neuroplastic changes occur in response to training. Previous studies show that transcranial alternating current stimulation (tACS), a form of non-invasive brain stimulation, can enhance encoding of a cognitive learning task during wakefulness. However, the effect of tACS on motor processes in the awake brain is unknown. In this study, forty-two healthy 18-35 year old participants received either 0.75 Hz (active) tACS (or sham stimulation) for 30 min during a ballistic thumb abduction motor training task. Training-related behavioural effects were quantified by assessing changes in thumb abduction acceleration, and neuroplastic changes were quantified by measuring motor evoked potential (MEP) amplitude of the abductor pollicis brevis muscle. These measures were reassessed immediately after the motor training task to quantify short-term changes, and then 24 h later to assess longer-term changes. Thumb abduction acceleration in both active and sham stimulation conditions increased immediately after the motor learning, consistent with effective training. Critically, participants in the active group maintained significantly higher thumb acceleration 24 h later (t40 = 2.810, P = 0.044). There were no significant changes or inter-group differences in MEPs for both conditions. The results suggest that 0.75 Hz tACS applied during motor training enhances the effectiveness of motor training, which manifests as enhancement in longer-term task benefits.

Phylogenomic analyses of mud dragons (Kinorhyncha).

Mud dragons (Kinorhyncha) are microscopic invertebrates, inhabiting marine sediments across the globe from intertidal to hadal depths. They are segmented, moulting animals like arthropods, but grouping with the unsegmented priapulans and loriciferans within Ecdysozoa. There are more than 300 species of kinorhynchs described within 31 genera and 11 families, however, their evolutionary relationships have so far only been investigated using morphology and a few molecular markers. Here we aim to resolve the relationships and classification of major clades within Kinorhyncha using transcriptomic data. In addition, we wish to revisit the position of three indistinctly segmented, aberrant genera in order to reconstruct the evolution of distinct segmentation within the group. We conducted a phylogenomic analysis of Kinorhyncha including 21 kinorhynch transcriptomes (of which 18 are new) representing 15 genera, and seven outgroups including priapulan, loriciferan, nematode and nematomorph transcriptomes. Results show a congruent and robust tree that supports the division of Kinorhyncha into two major clades: Cyclorhagida and Allomalorhagida. Cyclorhagida is composed of three subclades: Xenosomata, Kentrorhagata comb. nov. (including the aberrant Zelinkaderes) and Echinorhagata. Allomalorhagida is composed of two subclades: Pycnophyidae and Anomoirhaga nom. nov. Anomoirhaga nom. nov. accommodates the aberrant genera Cateria (previously nested within Cyclorhagida) and Franciscideres together with five additional genera. The distant and derived positions of the aberrant Zelinkaderes, Cateria and Franciscideres species suggest that their less distinct trunk segmentation evolved convergently, and that segmentation evolved among kinorhynch stem groups.

Reimagining the Clinical Competency Committee to Enhance Education and Prepare for Competency-Based Time-Variable Advancement.

Assessing residents and clinical fellows is a high-stakes activity. Effective assessment is important throughout training so that identified areas of strength and weakness can guide educational planning to optimize outcomes. Assessment has historically been underemphasized although medical education oversight organizations have strengthened requirements in recent years. Growing acceptance of competency-based medical education and its logical extension to competency-based time-variable (CB-TV) graduate medical education (GME) further highlights the importance of implementing effective evidence-based approaches to assessment. The Clinical Competency Committee (CCC) has emerged as a key programmatic structure in graduate medical education. In the context of launching a multi-specialty pilot of CB-TV GME in our health system, we have examined several program's CCC processes and reviewed the relevant literature to propose enhancements to CCCs. We recommend that all CCCs fulfill three core goals, regularly applied to every GME trainee: (1) discern and describe the resident's developmental status to individualize education, (2) determine readiness for unsupervised practice, and (3) foster self-assessment ability. We integrate the literature and observations from GME program CCCs in our institutions to evaluate how current CCC processes support or undermine these goals. Obstacles and key enablers are identified. Finally, we recommend ways to achieve the stated goals, including the following: (1) assess and promote the development of competency in all trainees, not just outliers, through a shared model of assessment and competency-based advancement; (2) strengthen CCC assessment processes to determine trainee readiness for independent practice; and (3) promote trainee reflection and informed self-assessment. The importance of coaching for competency, robust workplace-based assessments, feedback, and co-production of individualized learning plans are emphasized. Individual programs and their CCCs must strengthen assessment tools and frameworks to realize the potential of competency-oriented education.

Slow-oscillatory tACS does not modulate human motor cortical response to repeated plasticity paradigms.

Previous history of activity and learning modulates synaptic plasticity and can lead to saturation of synaptic connections. According to the synaptic homeostasis hypothesis, neural oscillations during slow-wave sleep play an important role in restoring plasticity within a functional range. However, it is not known whether slow-wave oscillations-without the concomitant requirement of sleep-play a causal role in human synaptic homeostasis. Here, we aimed to answer this question using transcranial alternating current stimulation (tACS) to induce slow-oscillatory activity in awake human participants. tACS was interleaved between two plasticity-inducing interventions: motor learning, and paired associative stimulation (PAS). The hypothesis tested was that slow-oscillatory tACS would prevent homeostatic interference between motor learning and PAS, and facilitate plasticity from these successive interventions. Thirty-six participants received sham and active fronto-motor tACS in two separate sessions, along with electroencephalography (EEG) recordings, while a further 38 participants received tACS through a control montage. Motor evoked potentials (MEPs) were recorded throughout the session to quantify plasticity changes after the different interventions, and the data were analysed with Bayesian statistics. As expected, there was converging evidence that motor training led to excitatory plasticity. Importantly, we found moderate evidence against an effect of active tACS in restoring PAS plasticity, and no evidence of lasting entrainment of slow oscillations in the EEG. This suggests that, under the conditions tested here, slow-oscillatory tACS does not modulate synaptic homeostasis in the motor system of awake humans.

Development and preliminary evaluation of the Neurofibromatosis Type 1 Adult Quality of Life (NF1-AdQoL) questionnaire.

BACKGROUND: Neurofibromatosis Type 1 (NF1) is a variable and unpredictable multisystem genetic disorder that predisposes to medical complications, cognitive impairment and disfigurement, of all which can impact negatively upon the health-related quality of life (HRQoL) of affected adults. AIMS: To develop and validate a disease-specific HRQoL adult questionnaire to evaluate effects of NF1 from the patient's viewpoint. METHODS: The Neurofibromatosis Type 1 Adult Health-related Quality of Life questionnaire (NF1-AdQoL) was based on patient interviews (n = 8), clinician survey and questionnaire pilot study. Adults with NF1 (n = 114, aged 18-40 years) were recruited from three Australian genetics clinics and completed the NF1-AdQoL, the 29-item Skindex (Skindex-29) and the 36-item Short Form, version 2 (SF-36v2) questionnaires. An exploratory factor analysis of the NF1-AdQoL was conducted to assess construct validity. Convergent and discriminant validity of the NF1-AdQoL was determined by using multitrait multimethod analysis with Skindex-29 and SF-36v2 scores. RESULTS: Factor analysis indicated that 62.7% of the common variance between the questionnaires could be explained by three factors: 'emotions associated with cosmetic appearance' (12 items), 'functioning - social and learning' (11 items) and 'physical symptoms' (8 items). NF1-AdQoL had good internal consistency (Cronbach α = 0.96). Convergent validity was confirmed by moderate associations with similarly named scales of the Skindex-29 and SF-36v2. Results from all three HRQoL questionnaires indicated overall healthy HRQoL for young to early middle-aged adults with NF1. CONCLUSION: The NF1-AdQoL is a relatively valid, feasible and fairly easy to read tool to measure the HRQoL of adults with NF1. Further evaluation is required to determine the test-retest reliability, responsiveness and validity of the NF1-AdQoL in larger adult NF1 cohorts.

Educating for adaptive expertise: case examples along the medical education continuum.

Adaptive expertise represents the combination of both efficient problem-solving for clinical encounters with known solutions, as well as the ability to learn and innovate when faced with a novel challenge. Fostering adaptive expertise requires careful approaches to instructional design to emphasize deeper, more effortful learning. These teaching strategies are time-intensive, effortful, and challenging to implement in health professions education curricula. The authors are educators whose missions encompass the medical education continuum, from undergraduate through to organizational learning. Each has grappled with how to promote adaptive expertise development in their context. They describe themes drawn from educational experiences at these various learner levels to illustrate strategies that may be used to cultivate adaptive expertise.At Vanderbilt University School of Medicine, a restructuring of the medical school curriculum provided multiple opportunities to use specific curricular strategies to foster adaptive expertise development. The advantage for students in terms of future learning had to be rationalized against assessments that are more short-term in nature. In a consortium of emergency medicine residency programs, a diversity of instructional approaches was deployed to foster adaptive expertise within complex clinical learning environments. Here the value of adaptive expertise approaches must be balanced with the efficiency imperative in clinical care. At Mayo Clinic, an existing continuous professional development program was used to orient the entire organization towards an adaptive expertise mindset, with each individual making a contribution to the shift.The different contexts illustrate both the flexibility of the adaptive expertise conceptualization and the need to customize the educational approach to the developmental stage of the learner. In particular, an important benefit of teaching to adaptive expertise is the opportunity to influence individual professional identity formation to ensure that clinicians of the future value deeper, more effortful learning strategies throughout their careers.

A Target Population Derived Method for Developing a Competency Standard in Radiograph Interpretation.

CONSTRUCT: For assessing the skill of visual diagnosis such as radiograph interpretation, competency standards are often developed in an ad hoc method, with a poorly delineated connection to the target clinical population. BACKGROUND: Commonly used methods to assess for competency in radiograph interpretation are subjective and potentially biased due to a small sample size of cases, subjective evaluations, or include an expert-generated case-mix versus a representative sample from the clinical field. Further, while digital platforms are available to assess radiograph interpretation skill against an objective standard, they have not adopted a data-driven competency standard which informs educators and the public that a physician has achieved adequate mastery to enter practice where they will be making high-stakes clinical decisions. APPROACH: Operating on a purposeful sample of radiographs drawn from the clinical domain, we adapted the Ebel Method, an established standard setting method, to ascertain a defensible, clinically relevant mastery learning competency standard for the skill of radiograph interpretation as a model for deriving competency thresholds in visual diagnosis. Using a previously established digital platform, emergency physicians interpreted pediatric musculoskeletal extremity radiographs. Using one-parameter item response theory, these data were used to categorize radiographs by interpretation difficulty terciles (i.e. easy, intermediate, hard). A panel of emergency physicians, orthopedic surgeons, and plastic surgeons rated each radiograph with respect to clinical significance (low, medium, high). These data were then used to create a three-by-three matrix where radiographic diagnoses were categorized by interpretation difficulty and significance. Subsequently, a multidisciplinary panel that included medical and parent stakeholders determined acceptable accuracy for each of the nine cells. An overall competency standard was derived from the weighted sum. Finally, to examine consequences of implementing this standard, we reported on the types of diagnostic errors that may occur by adhering to the derived competency standard. FINDINGS: To determine radiograph interpretation difficulty scores, 244 emergency physicians interpreted 1,835 pediatric musculoskeletal extremity radiographs. Analyses of these data demonstrated that the median interpretation difficulty rating of the radiographs was -1.8 logits (IQR -4.1, 3.2), with a significant difference of difficulty across body regions (p < 0.0001). Physician review classified the radiographs as 1,055 (57.8%) as low, 424 (23.1%) medium or 356 (19.1%) high clinical significance. The multidisciplinary panel suggested a range of acceptable scores between cells in the three-by-three table of 76% to 95% and the sum of equal-weighted scores resulted in an overall performance-based competency score of 85.5% accuracy. Of the 14.5% diagnostic interpretation errors that may occur at the bedside if this competency standard were implemented, 9.8% would be in radiographs of low-clinical significance, while 2.5% and 2.3% would be in radiographs of medium or high clinical significance, respectively. CONCLUSION(S): This study's novel integration of radiograph selection and a standard setting method could be used to empirically drive evidence-based competency standard for radiograph interpretation and can serve as a model for deriving competency thresholds for clinical tasks emphasizing visual diagnosis.

Miniaturizing Transmon Qubits Using van der Waals Materials.

Quantum computers can potentially achieve an exponential speedup versus classical computers on certain computational tasks, recently demonstrated in superconducting qubit processors. However, the capacitor electrodes that comprise these qubits must be large in order to avoid lossy dielectrics. This tactic hinders scaling by increasing parasitic coupling among circuit components, degrading individual qubit addressability, and limiting the spatial density of qubits. Here, we take advantage of the unique properties of van der Waals (vdW) materials to reduce the qubit area by >1000 times while preserving the capacitance while maintaining quantum coherence. Our qubits combine conventional aluminum-based Josephson junctions with parallel-plate capacitors composed of crystalline layers of superconducting niobium diselenide and insulating hexagonal boron nitride. We measure a vdW transmon T1 relaxation time of 1.06 µs, demonstrating a path to achieve high-qubit-density quantum processors with long coherence times, and the broad utility of layered heterostructures in low-loss, high-coherence quantum devices.