The RAG Model: a new paradigm for genetic risk stratification in multiple myeloma

Molecular studies have shown that multiple myeloma is a highly genetically heterogonous disease which may manifest itself as any number of diverse subtypes each with variable clinicopathological features and outcomes. Given this genetic heterogeneity, a universal approach to treatment of myeloma is unlikely to be successful for all patients and instead we should strive for the goal of personalised therapy using rationally informed targeted strategies. Current DNA sequencing technologies allow for whole genome and exome analysis of patient myeloma samples that yield vast amounts of genetic data and provide a mutational overview of the disease. However, the clinical utility of this information currently lags far behind the sequencing technology which is increasingly being incorporated into clinical practice. This paper attempts to address this shortcoming by proposing a novel genetically based “traffic-light” risk stratification system for myeloma, termed the RAG (Red, Amber, Green) model, which represents a simplified concept of how complex genetic data may be compressed into an aggregate risk score. The model aims to incorporate all known clinically important trisomies, translocations, and mutations in myeloma and utilise these to produce a score between 1.0 and 3.0 that can be incorporated into diagnostic, prognostic, and treatment algorithms for the patient

Three academics' narratives in transforming curriculum for education for sustainable development

The expectation is that higher education curricula which purports to incorporate education for sustainable development (ESD) supports university graduates in becoming more sustainable. It would then follow that if academics are to offer such curricula they need to be adequately equipped with the motivations, knowledge and skills to teach it. However, the extent to which ESD has resulted in genuine higher education curriculum change, and academic readiness for it, is debatable. As such, this article presents the academic experiences of three of the authors involved in a curriculum change process to embed ESD within a Bachelor of Arts (Textile Design) degree program. Individual post-project narratives of our experiences are summarised and thematically analysed. The analysis reveals these experiences as disorienting, yet subsequently transformative. The findings suggest promoting academics' transformative learning should be a focus of ESD curriculum change efforts. The findings support commitment to long-term, facilitated professional development to achieve transformative change; an often espoused, yet under-reported initiative

Computational fluid dynamic analysis of bioprinted self-supporting perfused tissue models

Natural tissues are incorporated with vasculature, which is further integrated with a cardiovascular system responsible for driving perfusion of nutrient‐rich oxygenated blood through the vasculature to support cell metabolism within most cell‐dense tissues. Since scaffold‐free biofabricated tissues being developed into clinical implants, research models, and pharmaceutical testing platforms should similarly exhibit perfused tissue‐like structures, we generated a generalizable biofabrication method resulting in self‐supporting perfused (SSuPer) tissue constructs incorporated with perfusible microchannels and integrated with the modular FABRICA perfusion bioreactor. As proof of concept, we perfused an MLO‐A5 osteoblast‐based SSuPer tissue in the FABRICA. Although our resulting SSuPer tissue replicated vascularization and perfusion observed in situ, supported its own weight, and stained positively for mineral using Von Kossa staining, our in vitro results indicated that computational fluid dynamics (CFD) should be used to drive future construct design and flow application before further tissue biofabrication and perfusion. We built a CFD model of the SSuPer tissue integrated in the FABRICA and analyzed flow characteristics (net force, pressure distribution, shear stress, and oxygen distribution) through five SSuPer tissue microchannel patterns in two flow directions and at increasing flow rates. Important flow parameters include flow direction, fully developed flow, and tissue microchannel diameters matched and aligned with bioreactor flow channels. We observed that the SSuPer tissue platform is capable of providing direct perfusion to tissue constructs and proper culture conditions (oxygenation, with controllable shear and flow rates), indicating that our approach can be used to biofabricate tissue representing primary tissues and that we can model the system in silico

High-resolution mapping of fluoroquinolones in TB rabbit lesions reveals specific distribution in immune cell types.

Understanding the distribution patterns of antibiotics at the site of infection is paramount to selecting adequate drug regimens and developing new antibiotics. Tuberculosis (TB) lung lesions are made of various immune cell types, some of which harbor persistent forms of the pathogen, Mycobacterium tuberculosis. By combining high resolution MALDI MSI with histology staining and quantitative image analysis in rabbits with active TB, we have mapped the distribution of a fluoroquinolone at high resolution, and identified the immune-pathological factors driving its heterogeneous penetration within TB lesions, in relation to where bacteria reside. We find that macrophage content, distance from lesion border and extent of necrosis drive the uneven fluoroquinolone penetration. Preferential uptake in macrophages and foamy macrophages, where persistent bacilli reside, compared to other immune cells present in TB granulomas, was recapitulated in vitro using primary human cells. A nonlinear modeling approach was developed to help predict the observed drug behavior in TB lesions. This work constitutes a methodological advance for the co-localization of drugs and infectious agents at high spatial resolution in diseased tissues, which can be applied to other diseases with complex immunopathology

Are medical students influenced by preceptors in making career choices, and if so how? A systematic review

A B S T R A C T Introduction: Increasingly medical students undertake clinical training in distributed learning environments. The driving factor for this is predominantly to address medical workforce shortages. In these environments students are often taught by private practitioners, residents, house staff and registrars, as well as faculty. Through a mix of short-and long-term preceptorships, clerkships and rotations, medical students are exposed to a wider range of preceptors, mentors and role models than has traditionally been the case. The aim of this systematic review was to understand if and how medical students' career choices are influenced by their interactions with preceptors. Method: A search of Ovid Medline, Scopus, ISI Web of Science, PubMed, Eric and CIHNAL was undertaken. The search was structured around the key terms: Medical Student, Career Choice and Preceptor, and variants of these terms. Search limits were set to English-language publications between 1995 and 2010. Results: A total of 36 articles met the selection criteria from the 533 citations sourced from the search. Required preceptorships as short as 3 weeks' duration influence the career choice of students when they rate the preceptor as a high quality teacher. Preceptors who are judged (by students) as high quality teachers have the greatest influence on student career choice by up to four-fold. When students judged a preceptor as being a negative role model, a poor teacher or lacking discipline specific knowledge they will turn away from that field. The positive influence of relationships between preceptors and students on career choice is strongest where Sweet, 2012. A licence to publish this material has been given to James Cook University, http://www.rrh.org.au 2 there is continuity of preceptors, continuity of care, and continuity of patient interactions. The longer the duration of the preceptorship the greater the influence on student career choice, particularly in primary cares environments. Conclusion: This review adds to the literature by identifying how differing components and combinations of components of a preceptorship influence medical student career choices. Multiple components of the preceptorship combined have a greater influence. In free choice, longitudinal integrated clerkships' duration of placement and continuity relationships with preceptors have the greatest influence on medical students in pursuing a primary care career. This information informs medical schools, curriculum designers and policy-makers in reforming medical education to address workforce shortages

Developing the accredited postgraduate assessment program for Fellowship of the Australian College of Rural and Remote Medicine

Introduction: Accreditation of the Australian College of Rural and Remote Medicine (ACRRM) as a standards and training provider, by the Australian Medical Council (AMC) in 2007, is the first time in the world that a peak professional organisation for rural and remote medical education has been formally recognised. As a consequence, the Australian Government provided rural and remote medicine with formal recognition under Medicare as a generalist discipline. This accreditation was based on the ability of ACRRM to meet the AMC's guidelines for its training and assessment program.\ud \ud Methods: The methodology was a six-step process that included: developing an assessment blueprint and a classification scheme; identifying an assessment model; choosing innovative summative and formative assessment methods that met the needs of rural and remote located medical practitioner candidates; 21 rural doctors and academics developing the assessment items as part of a week-long writing workshop; investigating the feasibility of purchasing assessment items; and 48 rural candidates piloting three of the assessment items to ensure they would meet the guidelines for national accreditation.\ud \ud Results: The project resulted in an innovative formative and summative assessment program that occurs throughout 4 years of vocational training, using innovative, reliable, valid and acceptable methods with educational impact. The piloting process occurred for 3 of the 6 assessment tools. Structured Assessment Using Multiple Patient Scenarios (StAMPS) is a new assessment method developed as part of this project. The StAMPS pilot found that it was reliable, with a generalisability coefficient of >0.76 and was a valid, acceptable and feasible assessment tool with desired educational impact. The multiple choice question (MCQ) examination pilot found that the applied clinical nature of the questions and their wide range of scenarios proved a very acceptable examination to the profession. The web based in-training assessment examination pilot revealed that it would serve well as a formative process until ACRRM can further develop their MCQ database.\ud \ud Conclusions: The ACRRM assessment program breaks new ground for assessing rural and remote doctors in Australia, and provides new evidence regarding how a comprehensive and contemporary assessment system can work within a postgraduate medical setting

Evaluation of a learner-designed course for teaching health research skills in Ghana

<p>Abstract</p> <p>Background</p> <p>In developing countries the ability to conduct locally-relevant health research and high quality education are key tools in the fight against poverty. The objective of our study was to evaluate the effectiveness of a novel UK accredited, learner-designed research skills course delivered in a teaching hospital in Ghana.</p> <p>Methods</p> <p>Study participants were 15 mixed speciality health professionals from Komfo Anokye Teaching Hospital, Kumasi, Ghana. Effectiveness measures included process, content and outcome indicators to evaluate changes in learners' confidence and competence in research, and assessment of the impact of the course on changing research-related thinking and behaviour. Results were verified using two independent methods.</p> <p>Results</p> <p>14/15 learners gained research competence assessed against UK Quality Assurance Agency criteria. After the course there was a 36% increase in the groups' positive responses to statements concerning confidence in research-related attitudes, intentions and actions. The greatest improvement (45% increase) was in learners' actions, which focused on strengthening institutional research capacity. 79% of paired before/after responses indicated positive changes in individual learners' research-related attitudes (n = 53), 81% in intention (n = 52) and 85% in action (n = 52). The course had increased learners' confidence to start and manage research, and enhanced life-long skills such as reflective practice and self-confidence. Doing their own research within the work environment, reflecting on personal research experiences and utilising peer support and pooled knowledge were critical elements that promoted learning.</p> <p>Conclusion</p> <p>Learners in Ghana were able to design and undertake a novel course that developed individual and institutional research capacity and met international standards. Learning by doing and a supportive peer community at work were critical elements in promoting learning in this environment where tutors were scarce. Our study provides a model for delivering and evaluating innovative educational interventions in developing countries to assess whether they meet external quality criteria and achieve their objectives.</p

The UK clinical aptitude test and clinical course performance at Nottingham: a prospective cohort study

Background The UK Clinical Aptitude Test (UKCAT) was introduced in 2006 as an additional tool for the selection of medical students. It tests mental ability in four distinct domains (Verbal Reasoning, Quantitative Reasoning, Abstract Reasoning, and Decision Analysis), and the results are available to students and admission panels in advance of the selection process. Our first study showed little evidence of any predictive validity for performance in the first two years of the Nottingham undergraduate course. The study objective was to determine whether the UKCAT scores had any predictive value for the later parts of the course, largely delivered via clinical placements. Methods Students entering the course in 2007 and who had taken the UKCAT were asked for permission to use their anonymised data in research. The UKCAT scores were incorporated into a database with routine pre-admission socio-demographics and subsequent course performance data. Correlation analysis was followed by hierarchical multivariate linear regression. Results The original study group comprised 204/254 (80%) of the full entry cohort. With attrition over the five years of the course this fell to 185 (73%) by Year 5. The Verbal Reasoning score and the UKCAT Total score both demonstrated some univariate correlations with clinical knowledge marks, and slightly less with clinical skills. No parts of the UKCAT proved to be an independent predictor of clinical course marks, whereas prior attainment was a highly significant predictor (p <0.001). Conclusions This study of one cohort of Nottingham medical students showed that UKCAT scores at admission did not independently predict subsequent performance on the course. Whilst the test adds another dimension to the selection process, its fairness and validity in selecting promising students remains unproven, and requires wider investigation and debate by other schools

A comprehensive database of quality-rated fossil ages for Sahul’s Quaternary vertebrates

Published: 19 July 2016The study of palaeo-chronologies using fossil data provides evidence for past ecological and evolutionary processes, and is therefore useful for predicting patterns and impacts of future environmental change. However, the robustness of inferences made from fossil ages relies heavily on both the quantity and quality of available data. We compiled Quaternary non-human vertebrate fossil ages from Sahul published up to 2013. This, the FosSahul database, includes 9,302 fossil records from 363 deposits, for a total of 478 species within 215 genera, of which 27 are from extinct and extant megafaunal species (2,559 records). We also provide a rating of reliability of individual absolute age based on the dating protocols and association between the dated materials and the fossil remains. Our proposed rating system identified 2,422 records with high-quality ages (i.e., a reduction of 74%). There are many applications of the database, including disentangling the confounding influences of hypothetical extinction drivers, better spatial distribution estimates of species relative to palaeo-climates, and potentially identifying new areas for fossil discovery.Marta Rodríguez-Rey, y, Salvador Herrando-Pérez, Barry W. Brook, Frédérik Saltré, John Alroy, Nicholas Beeton, Michael I. Bird, Alan Cooper, Richard Gillespie, Zenobia Jacobs, Christopher N. Johnson, Gifford H. Miller, Gavin J. Prideaux, Richard G. Roberts, Chris S.M. Turney and Corey J.A. Bradsha