A typology of longitudinal integrated clerkships

Context Longitudinal integrated clerkships (LICs) represent a model of the structural redesign of clinical education that is growing in the USA, Canada, Australia and South Africa. By contrast with time‐limited traditional block rotations, medical students in LICs provide comprehensive care of patients and populations in continuing learning relationships over time and across disciplines and venues. The evidence base for LICs reveals transformational professional and workforce outcomes derived from a number of small institution‐specific studies. Objectives This study is the first from an international collaborative formed to study the processes and outcomes of LICs across multiple institutions in different countries. It aims to establish a baseline reference typology to inform further research in this field. Methods Data on all LIC and LIC‐like programmes known to the members of the international Consortium of Longitudinal Integrated Clerkships were collected using a survey tool developed through a Delphi process and subsequently analysed. Data were collected from 54 programmes, 44 medical schools, seven countries and over 15 000 student‐years of LIC‐like curricula. Results Wide variation in programme length, student numbers, health care settings and principal supervision was found. Three distinct typological programme clusters were identified and named according to programme length and discipline coverage: Comprehensive LICs; Blended LICs, and LIC‐like Amalgamative Clerkships. Two major approaches emerged in terms of the sizes of communities and types of clinical supervision. These referred to programmes based in smaller communities with mainly family physicians or general practitioners as clinical supervisors, and those in more urban settings in which subspecialists were more prevalent. Conclusions Three distinct LIC clusters are classified. These provide a foundational reference point for future studies on the processes and outcomes of LICs. The study also exemplifies a collaborative approach to medical education research that focuses on typology rather than on individual programme or context

Biomarkers of apoptosis

Within the era of molecularly targeted anticancer agents, it has become increasingly important to provide proof of mechanism as early on as possible in the drug development cycle, especially in the clinic. Selective activation of apoptosis is often cited as one of the major goals of cancer chemotherapy. Thus, the present minireview focuses on a discussion of the pros and cons of a variety of methodological approaches to detect different components of the apoptotic cascade as potential biomarkers of programmed cell death. The bulk of the discussion centres on serological assays utilising the technique of ELISA, since here there is an obvious advantage of sampling multiple time points. Potential biomarkers of apoptosis including circulating tumour cells, cytokeratins and DNA nucleosomes are discussed at length. However, accepting that a single biomarker may not have the power to predict proof of concept and patient outcome, it is clear that in the future more emphasis will be placed on technologies that can analyse panels of biomarkers in small volumes of samples. To this end the increased throughput afforded by multiplex ELISA technologies is discussed

Engineering challenges of intrafirm technology reuse

Companies derive additional value from technological investments by repeatedly applying them across different product lines in their portfolios. Technology reuse strategies have helped to increase efficiency in leveraging research and development investments, but the attempts to explain how to duplicate such results for technology reuse at the engineering level are missing. While there are synergetic effects to the reuse of technologies, there are also transaction costs that limit the benefits in practice. This paper presents a model, along with three examples, of technology reuse to help account for these transaction costs and mitigate the fallacy of perceiving technologies as reusable “off‐the‐shelf” elements

In vitro and in vivo activity and cross resistance profiles of novel ruthenium (II) organometallic arene complexes in human ovarian cancer.

Ruthenium complexes offer the potential of reduced toxicity, a novel mechanism of action, non-cross resistance and a different spectrum of activity compared to platinum containing compounds. Thirteen novel ruthenium(II) organometallic arene complexes have been evaluated for activity (in vitro and in vivo) in models of human ovarian cancer, and cross-resistance profiles established in cisplatin and multi-drug-resistant variants. A broad range of IC50 values was obtained (0.5 to >100 microM) in A2780 parental cells with two compounds (RM175 and HC29) equipotent to carboplatin (6 microM), and the most active compound (HC11) equipotent to cisplatin (0.6 microM). Stable bi-dentate chelating ligands (ethylenediamine), a more hydrophobic arene ligand (tetrahydroanthracene) and a single ligand exchange centre (chloride) were associated with increased activity. None of the six active ruthenium(II) compounds were cross-resistant in the A2780cis cell line, demonstrated to be 10-fold resistant to cisplatin/carboplatin by a mechanism involving, at least in part, silencing of MLH1 protein expression via methylation. Varying degrees of cross-resistance were observed in the P-170 glycoprotein overexpressing multi-drug-resistant cell line 2780AD that could be reversed by co-treatment with verapamil. In vivo activity was established with RM175 in the A2780 xenograft together with non-cross-resistance in the A2780cis xenograft and a lack of activity in the 2780AD xenograft. High activity coupled to non cross-resistance in cisplatin resistant models merit further development of this novel group of anticancer compounds

The Faces in Infant-Perspective Scenes Change over the First Year of Life

Mature face perception has its origins in the face experiences of infants. However, little is known about the basic statistics of faces in early visual environments. We used head cameras to capture and analyze over 72,000 infant-perspective scenes from 22 infants aged 1-11 months as they engaged in daily activities. The frequency of faces in these scenes declined markedly with age: for the youngest infants, faces were present 15 minutes in every waking hour but only 5 minutes for the oldest infants. In general, the available faces were well characterized by three properties: (1) they belonged to relatively few individuals; (2) they were close and visually large; and (3) they presented views showing both eyes. These three properties most strongly characterized the face corpora of our youngest infants and constitute environmental constraints on the early development of the visual system

Observation of an Exotic S=+1S=+1 Baryon in Exclusive Photoproduction from the Deuteron

In an exclusive measurement of the reaction $\gamma d \to K^+ K^- p n$, a narrow peak that can be attributed to an exotic baryon with strangeness $S=+1$ is seen in the $K^+n$ invariant mass spectrum. The peak is at $1.542\pm 0.005$ GeV/c$^2$ with a measured width of 0.021 GeV/c$^2$ FWHM, which is largely determined by experimental mass resolution. The statistical significance of the peak is $5.2 \pm 0.6 \sigma$. The mass and width of the observed peak are consistent with recent reports of a narrow $S=+1$ baryon by other experimental groups.Comment: 5 pages, 5 figure