3,077 research outputs found

    Assessing Professionalism: A theoretical framework for defining clinical rotation assessment criteria

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    Although widely accepted as an important graduate competence, professionalism is a challenging outcome to define and assess. Clinical rotations provide an excellent opportunity to develop student professionalism through the use of experiential learning and effective feedback, but without appropriate theoretical frameworks, clinical teachers may find it difficult to identify appropriate learning outcomes. The adage “I know it when I see it” is unhelpful in providing feedback and guidance for student improvement, and criteria that are more specifically defined would help students direct their own development. This study sought first to identify how clinical faculty in one institution currently assess professionalism, using retrospective analysis of material obtained in undergraduate teaching and faculty development sessions. Subsequently, a faculty workshop was held in which a round-table type discussion sought to develop these ideas and identify how professionalism assessment could be improved. The output of this session was a theoretical framework for teaching and assessing professionalism, providing example assessment criteria and ideas for clinical teaching. This includes categories such as client and colleague interaction, respect and trust, recognition of limitations, and understanding of different professional identities. Each category includes detailed descriptions of the knowledge, skills, and behaviors expected of students in these areas. The criteria were determined by engaging faculty in the development of the framework, and therefore they should represent a focused development of criteria already used to assess professionalism, and not a novel and unfamiliar set of assessment guidelines. The faculty-led nature of this framework is expected to facilitate implementation in clinical teaching

    Opening the black box of mixed-metal TMP metallating reagents : direct cadmation or lithium-cadmium transmetallation?

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    Designed to remove some of the mystery surrounding mixed-metal TMP (2,2,6,6-tetramethylpiperidide) metallating reagents, this study examines in detail "LiCd(TMP)(3)'' in its own right. Previously established as an excellent "cadmating'' (Cd-H exchange) reagent towards a wide variety of aromatic substrates, "LiCd(TMP)(3)'' has been investigated by H-1, C-13 and Cd-113 NMR studies as well as by DOSY NMR spectroscopy. This evidence puts a question mark against its ate formulation implying it exists in THF solution as two independent homometallic amides. Exploring the reactivity of "LiCd(TMP)(3)'' with anisole as a test substrate, both experimentally by NMR studies and theoretically by DFT studies suggests a two-step lithiation/transmetallation process in which the initially formed ortho-lithiated species undergoes a reaction with Cd(TMP)(2) to form new Cd-C and Li-N bonds. For completeness, the homometallic cadmium component Cd(TMP)(2) has been comprehensively characterised for the first time including a crystal structure determination revealing a near-linear N-Cd-N arrangement

    Sizes, Shapes, and Correlations of Lyman Alpha Clouds and Their Evolution in the CDM+Λ+\Lambda Universe

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    This study analyzes the sizes, shapes and correlations of \lya clouds produced by a hydrodynamic simulation of a spatially flat CDM universe with a non-zero cosmological constant (Ω0=0.4\Omega_0=0.4, Λ0=0.6\Lambda_0=0.6, σ8=0.79\sigma_8 =0.79), over the redshift range 2z42\le z \le 4. The \lya clouds range in size from several kiloparsecs to about a hundred kiloparsecs in proper units, and they range in shape from roundish, high column density regions with \nhi\ge 10^{15} cm^{-2} to low column density sheet-like structures with \nhi \le 10^{13} cm^{-2} at z=3. The most common shape found in the simulation resembles that of a flattened cigar. The physical size of a typical cloud grows with time roughly as (1+z)3/2(1+z)^{-3/2} while its shape hardly evolves (except for the most dense regions ρcut>30\rho_{cut}>30). Our result indicates that any simple model with a population of spheres (or other shapes) of a uniform size is oversimplified; if such a model agrees with observational evidence, it is probably only by coincidence. We also illustrate why the use of double quasar sightlines to set lower limits on cloud sizes is useful only when the perpendicular sightline separation is small (Δr50h1\Delta r \le 50h^{-1} kpc). Finally, we conjecture that high column density \lya clouds (\nhi\ge 10^{15} cm^{-2}) may be the progenitors of the lower redshift faint blue galaxies. This seems plausible because their correlation length, number density (extrapolated to lower redshift) and their masses are in fair agreement with those observed.Comment: ApJ, in press, 34 pages, 21 figures, figs (1a,b,c) can be at http://astro.princeton.edu/~cen/LYASSC/lyassc.htm

    Gravitational collapse in an expanding background and the role of substructure II: Excess power at small scales and its effect of collapse of structures at larger scales

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    We study the interplay of clumping at small scales with the collapse and relaxation of perturbations at larger scales using N-Body simulations. We quantify the effect of collapsed haloes on perturbations at larger scales using two point correlation function, moments of counts in cells and mass function. The purpose of the study is twofold and the primary aim is to quantify the role played by collapsed low mass haloes in the evolution of perturbations at large scales, this is in view of the strong effect seen when the large scale perturbation is highly symmetric. Another reason for this study is to ask whether features or a cutoff in the initial power spectrum can be detected using measures of clustering at scales that are already non-linear. The final aim is to understand the effect of ignoring perturbations at scales smaller than the resolution of N-Body simulations. We find that these effects are ignorable if the scale of non-linearity is larger than the average inter-particle separation in simulations. Features in in the initial power spectrum can be detected easily if the scale of these features is in the linear regime, detecting such features becomes difficult as the relevant scales become non-linear. We find no effect of features in initial power spectra at small scales on the evolved power spectra at large scales. We may conclude that in general, the effect on evolution of perturbations at large scales of clumping on small scales is very small and may be ignored in most situations.Comment: Accepted for publication in MNRA

    Cofactor Molecules Maintain Infectious Conformation and Restrict Strain Properties in Purified Prions

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    Prions containing misfolded prion protein (PrP(Sc)) can be formed with cofactor molecules using the technique of serial protein misfolding cyclic amplification. However, it remains unknown whether cofactors materially participate in maintaining prion conformation and infectious properties. Here we show that withdrawal of cofactor molecules during serial propagation of purified recombinant prions caused adaptation of PrP(Sc) structure accompanied by a reduction in specific infectivity of >10(5)-fold, to undetectable levels, despite the ability of adapted “protein-only” PrP(Sc) molecules to self-propagate in vitro. We also report that changing only the cofactor component of a minimal reaction substrate mixture during serial propagation induced major changes in the strain properties of an infectious recombinant prion. Moreover, propagation with only one functional cofactor (phosphatidylethanolamine) induced the conversion of three distinct strains into a single strain with unique infectious properties and PrP(Sc) structure. Taken together, these results indicate that cofactor molecules can regulate the defining features of mammalian prions: PrP(Sc) conformation, infectivity, and strain properties. These findings suggest that cofactor molecules likely are integral components of infectious prions

    The effect of aspirin and eicosapentaenoic acid on urinary biomarkers of prostaglandin E2 synthesis and platelet activation in participants of the seAFOod polyp prevention trial

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    Urinary prostaglandin (PG) E metabolite (PGE-M) and 11-dehydro (d)-thromboxane (TX) B2 are biomarkers of cyclooxygenase-dependent prostanoid synthesis. We investigated (1) the effect of aspirin 300 mg daily and eicosapentaenoic acid (EPA) 2000 mg daily, alone and in combination, on urinary biomarker levels and, (2) whether urinary biomarker levels predicted colorectal polyp risk, during participation in the seAFOod polyp prevention trial. Urinary PGE-M and 11-d-TXB2 were measured by liquid chromatography-tandem mass spectrometry. The relationship between urinary biomarker levels and colorectal polyp outcomes was investigated using negative binomial (polyp number) and logistic (% with one or more polyps) regression models. Despite wide temporal variability in PGE-M and 11-d-TXB2 levels within individuals, both aspirin and, to a lesser extent, EPA decreased levels of both biomarkers (74% [P ≤.001] and 8% [P ≤.05] reduction in median 11-d-TXB2 values, respectively). In the placebo group, a high (quartile [Q] 2-4) baseline 11-d-TXB2 level predicted increased polyp number (incidence rate ratio [IRR] [95% CI] 2.26 [1.11,4.58]) and risk (odds ratio [95% CI] 3.56 [1.09,11.63]). A low (Q1) on-treatment 11-d-TXB2 level predicted reduced colorectal polyp number compared to placebo (IRR 0.34 [0.12,0.93] for combination aspirin and EPA treatment) compared to high on-treatment 11-d-TXB2 values (0.61 [0.34,1.11]). Aspirin and EPA both inhibit PGE-M and 11-d-TXB2 synthesis in keeping with shared in vivo cyclooxygenase inhibition. Colorectal polyp risk and treatment response prediction by 11-d-TXB2 is consistent with a role for platelet activation during early colorectal carcinogenesis. The use of urinary 11-d-TXB2 measurement for a precision approach to colorectal cancer risk prediction and chemoprevention requires prospective evaluation

    Plasma and rectal mucosal oxylipin levels during aspirin and eicosapentaenoic acid treatment in the seAFOod polyp prevention trial

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    BACKGROUND: Aspirin and eicosapentaenoic acid (EPA) have colorectal polyp prevention activity, alone and in combination. This study measured levels of plasma and rectal mucosal oxylipins in participants of the seAFOod 2 × 2 factorial, randomised, placebo-controlled trial, who received aspirin 300 mg daily and EPA 2000 mg free fatty acid, alone and in combination, for 12 months. METHODS: Resolvin (Rv) E1, 15-epi-lipoxin (LX) A4 and respective precursors 18-HEPE and 15-HETE (with chiral separation) were measured by ultra-high performance liquid chromatography-tandem mass spectrometry in plasma taken at baseline, 6 months and 12 months, as well as rectal mucosa obtained at trial exit colonoscopy at 12 months, in 401 trial participants. RESULTS: Despite detection of S- and R- enantiomers of 18-HEPE and 15-HETE in ng/ml concentrations, RvE1 or 15‑epi-LXA4 were not detected above a limit of detection of 20 pg/ml in plasma or rectal mucosa, even in individuals randomised to both aspirin and EPA. We have confirmed in a large clinical trial cohort that prolonged (12 months) treatment with EPA is associated with increased plasma 18-HEPE concentrations (median [inter-quartile range] total 18-HEPE 0.51 [0.21-1.95] ng/ml at baseline versus 0.95 [0.46-4.06] ng/ml at 6 months [P<0.0001] in those randomised to EPA alone), which correlate strongly with respective rectal mucosal 18-HEPE levels (r = 0.82; P<0.001), but which do not predict polyp prevention efficacy by EPA or aspirin. CONCLUSION: Analysis of seAFOod trial plasma and rectal mucosal samples has not provided evidence of synthesis of the EPA-derived specialised pro-resolving mediator RvE1 or aspirin-trigged lipoxin 15‑epi-LXA4. We cannot rule out degradation of individual oxylipins during sample collection and storage but readily measurable precursor oxylipins argues against widespread degradation
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