Narrative descriptions should replace grades and numerical ratings for clinical performance in medical education in the United States

Background: In medical education, evaluation of clinical performance is based almost universally on rating scales for defined aspects of performance and scores on examinations and checklists. Unfortunately, scores and grades do not capture progress and competence among learners in the complex tasks and roles required to practice medicine. While the literature suggests serious problems with the validity and reliability of ratings of clinical performance based on numerical scores, the critical issue is not that judgments about what is observed vary from rater to rater but that these judgments are lost when translated into numbers on a scale. As the Next Accreditation System of the Accreditation Council on Graduate Medical Education (ACGME) takes effect, medical educators have an opportunity to create new processes of evaluation to document and facilitate progress of medical learners in the required areas of competence. Proposal and initial experience: Narrative descriptions of learner performance in the clinical environment, gathered using a framework for observation that builds a shared understanding of competence among the faculty, promise to provide meaningful qualitative data closely linked to the work of physicians. With descriptions grouped in categories and matched to milestones, core faculty can place each learner along the milestones' continua of progress. This provides the foundation for meaningful feedback to facilitate the progress of each learner as well as documentation of progress toward competence. Implications: This narrative evaluation system addresses educational needs as well as the goals of the Next Accreditation System for explicitly documented progress. Educators at other levels of education and in other professions experience similar needs for authentic assessment and, with meaningful frameworks that describe roles and tasks, may also find useful a system built on descriptions of learner performance in actual work settings. Conclusions: We must place medical learning and assessment in the contexts and domains in which learners do clinical work. The approach proposed here for gathering qualitative performance data in different contexts and domains is one step along the road to moving learners toward competence and mastery

Allosteric activation of the nitric oxide receptor soluble guanylate cyclase mapped by cryo-electron microscopy.

Soluble guanylate cyclase (sGC) is the primary receptor for nitric oxide (NO) in mammalian nitric oxide signaling. We determined structures of full-length Manduca sexta sGC in both inactive and active states using cryo-electron microscopy. NO and the sGC-specific stimulator YC-1 induce a 71° rotation of the heme-binding β H-NOX and PAS domains. Repositioning of the β H-NOX domain leads to a straightening of the coiled-coil domains, which, in turn, use the motion to move the catalytic domains into an active conformation. YC-1 binds directly between the β H-NOX domain and the two CC domains. The structural elongation of the particle observed in cryo-EM was corroborated in solution using small angle X-ray scattering (SAXS). These structures delineate the endpoints of the allosteric transition responsible for the major cyclic GMP-dependent physiological effects of NO

Coherent Coupled Qubits for Quantum Annealing

Quantum annealing is an optimization technique which potentially leverages quantum tunneling to enhance computational performance. Existing quantum annealers use superconducting flux qubits with short coherence times limited primarily by the use of large persistent currents I[subscript p]. Here, we examine an alternative approach using qubits with smaller I[subscript p] and longer coherence times. We demonstrate tunable coupling, a basic building block for quantum annealing, between two flux qubits with small (approximately 50-nA) persistent currents. Furthermore, we characterize qubit coherence as a function of coupler setting and investigate the effect of flux noise in the coupler loop on qubit coherence. Our results provide insight into the available design space for next-generation quantum annealers with improved coherence.United States. Office of the Director of National IntelligenceUnited States. Intelligence Advanced Research Projects ActivityUnited States. Dept. of Defense. Assistant Secretary of Defense for Research & Engineering (FA8721-05-C-0002

One-year outcomes after transcatheter insertion of an interatrial shunt device for the management of heart failure with preserved ejection fraction

Background—Heart failure with preserved ejection fraction has a complex pathophysiology and remains a therapeutic challenge. Elevated left atrial pressure, particularly during exercise, is a key contributor to morbidity and mortality. Preliminary analyses have demonstrated that a novel interatrial septal shunt device that allows shunting to reduce the left atrial pressure provides clinical and hemodynamic benefit at 6 months. Given the chronicity of heart failure with preserved ejection fraction, evidence of longer-term benefit is required. Methods and Results—Patients (n=64) with left ventricular ejection fraction ≥40%, New York Heart Association class II–IV, elevated pulmonary capillary wedge pressure (≥15 mm Hg at rest or ≥25 mm Hg during supine bicycle exercise) participated in the open-label study of the interatrial septal shunt device. One year after interatrial septal shunt device implantation, there were sustained improvements in New York Heart Association class (P<0.001), quality of life (Minnesota Living with Heart Failure score, P<0.001), and 6-minute walk distance (P<0.01). Echocardiography showed a small, stable reduction in left ventricular end-diastolic volume index (P<0.001), with a concomitant small stable increase in the right ventricular end-diastolic volume index (P<0.001). Invasive hemodynamic studies performed in a subset of patients demonstrated a sustained reduction in the workload corrected exercise pulmonary capillary wedge pressure (P<0.01). Survival at 1 year was 95%, and there was no evidence of device-related complications. Conclusions—These results provide evidence of safety and sustained clinical benefit in heart failure with preserved ejection fraction patients 1 year after interatrial septal shunt device implantation. Randomized, blinded studies are underway to confirm these observations

Unitarity Bounds for Gauged Axionic Interactions and the Green-Schwarz Mechanism

We analyze the effective actions of anomalous models in which a four-dimensional version of the Green-Schwarz mechanism is invoked for the cancellation of the anomalies, and we compare it with those models in which gauge invariance is restored by the presence of a Wess-Zumino term. Some issues concerning an apparent violation of unitarity of the mechanism, which requires Dolgov-Zakharov poles, are carefully examined, using a class of amplitudes studied in the past by Bouchiat-Iliopoulos-Meyer (BIM), and elaborating on previous studies. In the Wess-Zumino case we determine explicitly the unitarity bound using a realistic model of intersecting branes (the Madrid model) by studying the corresponding BIM amplitudes. This is shown to depend significantly on the St\"uckelberg mass and on the coupling of the extra anomalous gauge bosons and allows one to identify Standard-Model-like regions (which are anomaly-free) from regions where the growth of certain amplitudes is dominated by the anomaly, separated by an inflection point which could be studied at the LHC. The bound can even be around 5-10 TeV's for a $Z'$ mass around 1 TeV and varies sensitively with the anomalous coupling. The results for the WZ case are quite general and apply to all the models in which an axion-like interaction is introduced as a generalization of the Peccei-Quinn mechanism, with a gauged axion.Comment: 50 pages, 28 figure

The flux qubit revisited to enhance coherence and reproducibility

The scalable application of quantum information science will stand on reproducible and controllable high-coherence quantum bits (qubits). Here, we revisit the design and fabrication of the superconducting flux qubit, achieving a planar device with broad-frequency tunability, strong anharmonicity, high reproducibility and relaxation times in excess of 40 μs at its flux-insensitive point. Qubit relaxation times T₁ across 22 qubits are consistently matched with a single model involving resonator loss, ohmic charge noise and 1/f-flux noise, a noise source previously considered primarily in the context of dephasing. We furthermore demonstrate that qubit dephasing at the flux-insensitive point is dominated by residual thermal-photons in the readout resonator. The resulting photon shot noise is mitigated using a dynamical decoupling protocol, resulting in T₂≈85 μs, approximately the 2T₁ limit. In addition to realizing an improved flux qubit, our results uniquely identify photon shot noise as limiting T₂ in contemporary qubits based on transverse qubit–resonator interaction

Low Dose Daily Iron Supplementation Improves Iron Status and Appetite but not Anemia, Whereas Quarterly Anthelminthic Treatment Improves Growth, Appetite and Anemia in Zanzibari Preschool Children.

Iron deficiency and helminth infections are two common conditions of children in developing countries. The consequences of helminth infection in young children are not well described, and the efficacy of low dose iron supplementation is not well documented in malaria-endemic settings. A 12-mo randomized, placebo controlled, double-blind trial of 10 mg daily iron and/or mebendazole (500 mg) every 3 mo was conducted in a community-based sample of 459 Zanzibari children age 6-71 mo with hemoglobin > 70 g/L at baseline. The trial was designed to examine treatment effects on growth, anemia and appetite in two age subgroups. Iron did not affect growth retardation, hemoglobin concentration or mild or moderate anemia (hemoglobin < 110 g/L or < 90 g/L, respectively), but iron significantly improved serum ferritin and erythrocyte protoporphyrin. Mebendazole significantly reduced wasting malnutrition. but only in children <30 mo old. The adjusted odds ratios (AORs) for mebendazole in this age group were 0.38 (95% CI: 0.16, 0.90) for weight-for-height less than -1 Z-score and 0.29 (0.09, 0.91) for small arm circumference. In children <24 mo old, mebendazole also reduced moderate anemia (AOR: 0.41, 0.18, 0.94). Both iron and mebendazole improved children's appetite, according to mothers' report. In this study, iron's effect on anemia was limited, likely constrained by infection, inflammation and perhaps other nutrient deficiencies. Mebendazole treatment caused unexpected and significant reductions in wasting malnutrition and anemia in very young children with light infections. We hypothesize that incident helminth infections may stimulate inflammatory immune responses in young children, with deleterious effects on protein metabolism and erythropoiesis

Inflammation-induced effector CD4+ T cell interstitial migration is alpha-v integrin dependent

Leukocytes must traverse inflamed tissues to effectively control local infection. Although motility in dense tissues appears to be integrin-independent actin-myosin based, during inflammation changes to the extracellular matrix (ECM) may necessitate distinct motility requirements. Indeed, we found that T cell interstitial motility was critically dependent on RGD-binding integrins in the inflamed dermis. Inflammation-induced deposition of fibronectin was functionally linked to increased αv integrin expression on effector CD4+ T cells. Using intravital multi-photon imaging, we found that CD4+ T cell motility was dependent on αv expression. Selective αv blockade or knockdown arrested TH1 motility in the inflamed tissue and attenuated local effector function. These data show a context-dependent specificity of lymphocyte movement in inflamed tissues that is essential for protective immunity

The science of clinical practice: disease diagnosis or patient prognosis? Evidence about "what is likely to happen" should shape clinical practice.

BACKGROUND: Diagnosis is the traditional basis for decision-making in clinical practice. Evidence is often lacking about future benefits and harms of these decisions for patients diagnosed with and without disease. We propose that a model of clinical practice focused on patient prognosis and predicting the likelihood of future outcomes may be more useful. DISCUSSION: Disease diagnosis can provide crucial information for clinical decisions that influence outcome in serious acute illness. However, the central role of diagnosis in clinical practice is challenged by evidence that it does not always benefit patients and that factors other than disease are important in determining patient outcome. The concept of disease as a dichotomous 'yes' or 'no' is challenged by the frequent use of diagnostic indicators with continuous distributions, such as blood sugar, which are better understood as contributing information about the probability of a patient's future outcome. Moreover, many illnesses, such as chronic fatigue, cannot usefully be labelled from a disease-diagnosis perspective. In such cases, a prognostic model provides an alternative framework for clinical practice that extends beyond disease and diagnosis and incorporates a wide range of information to predict future patient outcomes and to guide decisions to improve them. Such information embraces non-disease factors and genetic and other biomarkers which influence outcome. SUMMARY: Patient prognosis can provide the framework for modern clinical practice to integrate information from the expanding biological, social, and clinical database for more effective and efficient care

The clinical significance of tumor infiltrating lymphoctyes in breast cancer: does subtype matter?

Tumor infiltrating lymphocytes (TILs) are commonly detected in breast tumors but their bearing on disease outcome is uncertain. The importance of TILs appears to be subtype-specific and varies depending on the histologic characteristics of the tumor. As our understanding of tumorigenesis is increasing the relevance of immunobiology will become apparent