Vitalizing the evaluation of curricular implementation: a framework for attending to the "how and whys" of curriculum evolution.

As curricular reforms are implemented, there is often urgency among scholars to swiftly evaluate curricular outcomes and establish whether desired impacts have been realized. Consequently, many evaluative studies focus on summative program outcomes without accompanying evaluations of implementation. This runs the risk of Type III errors, whereby outcome evaluations rest on unverified assumptions about the appropriate implementation of prescribed curricular activities. Such errors challenge the usefulness of the evaluative studies, casting doubt on accumulated knowledge about curricular innovations, and posing problems for educational systems working to mobilize scarce resources. Unfortunately, however, there is long-standing inattention to the evaluation of implementation in health professions education (HPE). To address this, we propose an accessible framework that provides substantive guidance for evaluative research on implementation of curricular innovations. The Prescribed-Intended-Enacted-Sustainable (PIES) framework that is articulated in this paper, introduces new concepts to HPE-with a view to facilitating more nuanced examination of the evolution of curricula as they are implemented. Critically, the framework is theoretically grounded, integrating evaluation and implementation science as well as education theory. It outlines when, how, and why evaluators need to direct attention to curricular implementation, providing guidance on how programs can map out meaningful evaluative research agendas. Ultimately, this work is intended to support evaluators and educators, seeking to design evaluation studies that provide more faithful, useful representations of the intricacies of curricular change implementation.

Understanding the surgical care needs and use of outpatient surgical care services among homeless patients at the Ottawa Hospital

Background: The use of outpatient health care services by homeless people is low compared to their high level of need; however, it is unclear whether this applies to surgical care. We sought to describe surgical care access among homeless patients in a Canadian tertiary care setting. Methods: We reviewed the medical records of adult (age > 18 yr) patients with no fixed address or a shelter address who presented to The Ottawa Hospital Emergency Department from Jan. 1, 2013, to Dec. 31, 2014, and required surgical referral. We analyzed the data using descriptive statistics. Results: A surgical referral was initiated in 129 emergency department visits for 97 patients (77 men [79%], mean age 46.7 yr). Most patients lived in shelters (77 [79%]) and had provincial health insurance (82 [84%]), but only 35 (36%) had a primary care physician. The mean number visits for any reason was 7.9 (standard deviation 13.7) (range 1­106). The majority of surgical referrals (83 [64.3%]) were for traumatic injuries, and the most frequently consulted service (52 [40.3%]) was orthopedic surgery. Just under half (48 [49%]) of referred patients attended at least 1 outpatient appointment, and only a third (33 [34%]) completed full follow-up. Conclusion: Homeless patients presenting to an emergency department and requiring surgical care were predominantly men living in shelters, most frequently seeking care for traumatic injuries. Current outpatient services may not meet the surgical care needs of these patients, as many do not access them. Alternative approaches to outpatient care must be considered, particularly among high-need services such as orthopedics, to support surgical care access among this population.

Contexte: L'utilisation des services de santé ambulatoires par les sans-abri est faible si on la compare à leurs besoins qui sont élevés; on ignore par contre s'il en va de même pour les soins chirurgicaux. Nous avons voulu décrire l'accès aux soins chirurgicaux chez les patients sans domicile fixe dans un hôpital de soins tertiaires au Canada. Méthodes: Nous avons passé en revue les dossiers médicaux de patients adultes (âge > 18 ans) sans domicile fixe ayant consulté aux urgences de l'Hôpital d'Ottawa entre le 1er janvier 2013 et le 31 décembre 2014, et pour qui une consultation en chirurgie avait été demandée. Nous avons analysé les données au moyen de statistiques descriptives. Résultats: Une consultation en chirurgie a été demandée lors de 129 visites aux urgences, pour 97 patients (77 hommes [79 %], âge moyen 46,7 ans). La plupart de ces patients vivaient dans des refuges (77 [79 %]) et bénéficiaient d'un régime d'assurance maladie provincial (82 [84 %]), mais seulement 35 (36 %) avaient un médecin de famille. Le nombre moyen de visites, toutes raisons confondues, a été de 7,9 (écart-type 13,7) (entre 1 et 106). La majorité des demandes de consultations en chirurgie (83 [64,3 %]) concernaient des lésions traumatiques et le service le plus souvent appelé en consultation (52 [40,3 %]) était la chirurgie orthopédique. Un peu moins de la moitié (48 [49 %]) des patients envoyés en consultation se sont présentés à au moins un rendez-vous en clinique externe, et seulement le tiers d'entre eux (33 [34 %]) se sont soumis au suivi complet. Conclusion: Les patients sans domicile fixe qui consultent aux urgences et ont besoin de soins chirurgicaux étaient principalement des hommes hébergés dans des refuges ayant le plus souvent consulté pour des blessures traumatiques. Les services ambulatoires actuels ne répondent peut-être pas aux besoins chirurgicaux de ces patients, car plusieurs n'y accèdent pas. Il faudrait envisager d'autres approches, particulièrement en ce qui concerne les services très en demande, comme l'orthopédie, pour faciliter l'accès aux soins chez cette population.

Binding Kinetics of Methylene Blue on Monolayer Graphene Investigated by Multiparameter Surface Plasmon Resonance.

In this paper, we study the interaction of a small dye molecule, namely, methylene blue (MB) with graphene surfaces using surface plasmon resonance (SPR). We show that by utilizing all of the parameters of the SPR angular dip and exploiting the fact that MB absorbs light at the operating wavelength, it is possible to detect the binding of small molecules that would otherwise not give a significant signal. The binding of MB to unmodified graphene is found to be stronger than that for gold. By studying the interaction at modified surfaces, we demonstrate that electrostatic effects play a dominant role in the binding of MB on to graphene. Furthermore, following the binding kinetics at various concentrations allows us to estimate apparent equilibrium binding and rate constants for the interaction of MB with graphene.

Does medical school research productivity predict a resident's research productivity during residency?

BACKGROUND: Research productivity is an important component of the CanMEDS Scholar role and is an accreditation requirement of Canadian Otolaryngology training programs. Our objective was to determine if an association exists between publication rates before and during Otolaryngology residency. METHODS: We obtained the names for all certified Canadian Otolaryngologists who graduated between 1998 and 2013 inclusive, and conducted a Medline search for all of their publications. Otolaryngologists were subgrouped based on year of residency graduation and the number of articles published pre-residency and during residency (0 or ≥1). Chi-squared analyses were used to evaluate whether publications pre-residency and year of graduation were associated with publications during residency. RESULTS: We obtained data for 312 Canadian Otolaryngologists. Of those 312 graduates, 46 (14.7%) had no identifiable publications on PubMed and were excluded from the final data analysis. Otolaryngology residents had a mean 0.65 (95% CI 0.50-0.80) publications before residency and 3.35 (95% CI 2.90-3.80) publications during residency. Between 1998 and 2013, mean publication rates before and during residency both increased significantly (R 2 = 0.594 and R 2 = 0.759, respectively), whereas publication rates after residency graduation has stagnated (R 2 = 0.023). The odds of publishing during residency was 5.85 times higher (95% CI 2.69-12.71) if a resident published prior to residency (p < 0.0001). The Spearman correlation coefficient between publications before and during residency is 0.472 (p < 0.0001). CONCLUSION: Residents who publish at least one paper before residency are nearly six times as likely to publish during residency than those who did not publish before residency. These findings may help guide Otolaryngology program selection committees in ranking the best CaRMS candidates.

Real-Time Label-Free Direct Electronic Monitoring of Topoisomerase Enzyme Binding Kinetics on Graphene.

Monolayer graphene field-effect sensors operating in liquid have been widely deployed for detecting a range of analyte species often under equilibrium conditions. Here we report on the real-time detection of the binding kinetics of the essential human enzyme, topoisomerase I interacting with substrate molecules (DNA probes) that are immobilized electrochemically on to monolayer graphene strips. By monitoring the field-effect characteristics of the graphene biosensor in real-time during the enzyme-substrate interactions, we are able to decipher the surface binding constant for the cleavage reaction step of topoisomerase I activity in a label-free manner. Moreover, an appropriate design of the capture probes allows us to distinctly follow the cleavage step of topoisomerase I functioning in real-time down to picomolar concentrations. The presented results are promising for future rapid screening of drugs that are being evaluated for regulating enzyme activity.

Tuning the isoelectric point of graphene by electrochemical functionalization.

The ability to control the charge-potential landscape at solid-liquid interfaces is pivotal to engineer novel devices for applications in sensing, catalysis and energy conversion. The isoelectric point (pI)/point of zero charge (pzc) of graphene plays a key role in a number of physico-chemical phenomena occurring at the graphene-liquid interface. Supported by theory, we present here a methodology to identify the pI/pzc of (functionalized) graphene, which also allows for estimating the nature and extent of ion adsorption. The pI of bare graphene (as-prepared, chemical vapor deposition (CVD)-grown) is found to be less than 3.3, which we can continuously modify up to 7.5 by non-covalent electrochemical attachment of aromatic amino groups, preserving the favorable electronic properties of graphene throughout. Modelling all the observed results with detailed theory, we also show that specific adsorption of ions and the substrate play only an ancillary role in our capability to tune the pI of graphene.

Identifying chemical functionalization on individual carbon nanotubes and graphene by local vibrational fingerprinting.

Chemical functionalization of carbon nanotubes (CNTs) and graphene allows for fine-tuning their physical and chemical properties to realize fascinating new fundamental phenomena as well as exotic applications. A primary challenge in such endeavors is the need to identify the chemical nature of attached functionalities at a single-nano-object level in a spatially resolved manner. Here we report the vibrational fingerprinting of functional groups that are attached to individual CNTs and graphene flakes. In order to achieve this, we decorate noncovalently functionalized CNTs and graphene with nanoparticles, which leads to the appearance of Raman peaks that can be correlated with the vibrational modes characteristic of the functional groups with diffraction-limited spatial resolution. The presented strategy is generic enough to be extended to other chemical modification routes on a range of nanostructures and hence will allow for rapid characterization of chemical modification of individual (semi)conducting nanostructures.

Mutations of human DNA topoisomerase I at poly(ADP-ribose) binding sites: modulation of camptothecin activity by ADP-ribose polymers.

BACKGROUND: DNA topoisomerases are key enzymes that modulate the topological state of DNA through the breaking and rejoining of DNA strands. Human topoisomerase I belongs to the family of poly(ADP-ribose)-binding proteins and is the target of camptothecin derived anticancer drugs. Poly(ADP-ribosyl)ation occurs at specific sites of the enzyme inhibiting the cleavage and enhancing the religation steps during the catalytic cycle. Thus, ADP-ribose polymers antagonize the activity of topoisomerase I poisons, whereas PARP inhibitors increase their antitumor effects. METHODS: Using site-directed mutagenesis we have analyzed the interaction of human topoisomerase I and poly(ADP-ribose) through enzymatic activity and binding procedures. RESULTS: Mutations of the human topoisomerase I hydrophobic or charged residues, located on the putative polymer binding sites, are not sufficient to abolish or reduce the binding of the poly(ADP-ribose) to the protein. These results suggest either the presence of additional binding sites or that the mutations are not enough perturbative to destroy the poly(ADP-ribose) interaction, although in one mutant they fully abolish the enzyme activity. CONCLUSIONS: It can be concluded that mutations at the hydrophobic or charged residues of the putative polymer binding sites do not interfere with the ability of poly(ADP-ribose) to antagonize the antitumor activity of topoisomerase I poisons.

Rolling circle amplification-based detection of human topoisomerase I activity on magnetic beads.

A high-sensitivity assay has been developed for the detection of human topoisomerase I with single molecule resolution. The method uses magnetic sepharose beads to concentrate rolling circle products, produced by the amplification of DNA molecules circularized by topoisomerase I and detectable with a confocal microscope as single and discrete dots, once reacted with fluorescent probes. Each dot, corresponding to a single cleavage-religation event mediated by the enzyme, can be counted due to its high signal/noise ratio, allowing detection of 0.3pM enzyme and representing a valid method to detect the enzyme activity in highly diluted samples.

The human topoisomerase 1B Arg634Ala mutation results in camptothecin resistance and loss of inter-domain motion correlation.

Human topoisomerase 1B, the unique target of the natural anticancer compound camptothecin, catalyzes the unwinding of supercoiled DNA by introducing transient single strand nicks and providing covalent protein-DNA adducts. The functional properties and the drug reactivity of the single Arg634Ala mutant have been investigated in comparison to the wild type enzyme. The mutant is characterized by an identical relaxation and cleavage rate but it displays resistance to camptothecin as indicated by a viability assay of the yeast cells transformed with the mutated protein. The mutant also displays a very fast religation rate that is only partially reduced by the presence of the drug, suggesting that this is the main reason for its resistance. A comparative analysis of the structural-dynamical properties of the native and mutant proteins by molecular dynamics simulation indicates that mutation of Arg634 brings to a loss of motion correlation between the different domains and in particular between the linker and the C-terminal domain, containing the catalytic tyrosine residue. These results indicate that the loss of motion correlation and the drug resistance are two strongly correlated events.

Molecular mechanism of the camptothecin resistance of Glu710Gly topoisomerase IB mutant analyzed in vitro and in silico.

BACKGROUND: DNA topoisomerases are key enzymes that modulate the topological state of DNA through the breaking and rejoining of DNA strands. Human topoisomerase IB can be inhibited by several compounds that act through different mechanisms, including clinically used drugs, such as the derivatives of the natural compound camptothecin that reversibly bind the covalent topoisomerase-DNA complex, slowing down the religation of the cleaved DNA strand, thus inducing cell death. Three enzyme mutations, which confer resistance to irinotecan in an adenocarcinoma cell line, were recently identified but the molecular mechanism of resistance was unclear. METHODS: The three resistant mutants have been investigated in S. cerevisiae model system following their viability in presence of increasing amounts of camptothecin. A systematical analysis of the different catalytic steps has been made for one of these mutants (Glu710Gly) and has been correlated with its structural-dynamical properties studied by classical molecular dynamics simulation. RESULTS: The three mutants display a different degree of camptothecin resistance in a yeast cell viability assay. Characterization of the different steps of the catalytic cycle of the Glu710Gly mutant indicated that its resistance is related to a high religation rate that is hardly affected by the presence of the drug. Analysis of the dynamic properties through simulation indicate that the mutant displays a much lower degree of correlation in the motion between the different protein domains and that the linker almost completely loses its correlation with the C-terminal domain, containing the active site tyrosine. CONCLUSIONS: These results indicate that a fully functional linker is required to confer camptothecin sensitivity to topoisomerase I since the destabilization of its structural-dynamical properties is correlated to an increase of religation rate and drug resistance.

Replacement of the human topoisomerase linker domain with the plasmodial counterpart renders the enzyme camptothecin resistant.

A human/plasmodial hybrid enzyme, generated by swapping the human topoisomerase IB linker domain with the corresponding domain of the Plasmodium falciparum enzyme, has been produced and characterized. The hybrid enzyme displays a relaxation activity comparable to the human enzyme, but it is characterized by a much faster religation rate. The hybrid enzyme is also camptothecin resistant. A 3D structure of the hybrid enzyme has been built and its structural-dynamical properties have been analyzed by molecular dynamics simulation. The analysis indicates that the swapped plasmodial linker samples a conformational space much larger than the corresponding domain in the human enzyme. The large linker conformational variability is then linked to important functional properties such as an increased religation rate and a low drug reactivity, demonstrating that the linker domain has a crucial role in the modulation of the topoisomerase IB activity.

A small organic compound enhances the religation reaction of human topoisomerase I and identifies crucial elements for the religation mechanism.

The different steps of the human Top1 (topoisomerase I) catalytic cycle have been analysed in the presence of a pentacyclic-diquinoid synthetic compound. The experiments indicate that it efficiently inhibits the cleavage step of the enzyme reaction, fitting well into the catalytic site. Surprisingly the compound, when incubated with the binary topoisomerase-DNA cleaved complex, helps the enzyme to remove itself from the cleaved DNA and close the DNA gap, increasing the religation rate. The compound also induces the religation of the stalled enzyme-CPT (camptothecin)-DNA ternary complex. Analysis of the molecule docked over the binary complex, together with its chemical properties, suggests that the religation enhancement is due to the presence on the compound of two oxygen atoms that act as hydrogen acceptors. This property facilitates the deprotonation of the 5' DNA end, suggesting that this is the limiting step in the topoisomerase religation mechanism.

Effectiveness of interventions to reduce aggression and injuries among ice hockey players: a systematic review.

BACKGROUND: The increasing incidence of injuries related to playing ice hockey is an important public health issue. We conducted a systematic review to evaluate the effectiveness of interventions designed to reduce injuries related to aggressive acts in ice hockey. METHODS: We identified relevant articles by searching electronic databases from their inception through July 2012, by using Internet search engines, and by manually searching sports medicine journals, the book series Safety in Ice Hockey and reference lists of included articles. We included studies that evaluated interventions to reduce aggression-related injuries and reported ratings of aggressive behaviour or rates of penalties or injuries. RESULTS: We identified 18 eligible studies. Most involved players in minor hockey leagues. Of 13 studies that evaluated changes in mandatory rules intended to lessen aggression (most commonly the restriction of body-checking), 11 observed a reduction in penalty or injury rates associated with rule changes, and 9 of these showed a statistically significant decrease. The mean number of penalties decreased by 1.2-5.9 per game, and injury rates decreased 3- to 12-fold. All 3 studies of educational interventions showed a reduction in penalty rates, but they were not powered or designed to show a change in injury rates. In 2 studies of cognitive behavioural interventions, reductions in aggressive behaviours were observed. INTERPRETATION: Changes to mandatory rules were associated with reductions in penalties for aggressive acts and in injuries related to aggression among ice hockey players. Effects of educational and cognitive behavioural interventions on injury rates are less clear. Well-designed studies of multifaceted strategies that combine such approaches are required.