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

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

The impact of high-speed railway on tourism spatial structures between two adjoining metropolitan cities in China: Beijing and Tianjin

This study examines the impact of HSR services on the tourism spatial interactions between Beijing and Tianjin in China. Data were collected from official statistical reports. A method of derivation was developed and several indexes, such as tourism mean center, and tourism standard distance are further applied to measure temporal-spatial changes between the two adjoining cities. The results reveal the dynamic tourism spatial interaction between Beijing and Tianjin has been influenced by a range of factors including population, destination attractiveness, disposable income and income elasticity, changes in the domestic and international spatial structure of tourist flows and how destination management organizations react to the changes. The study has implications for both the research and practice of city transportation and tourism development

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

The Constructivist Approach to Mathematics Teaching and the Active Learning Strategies used to Enhance Student Understanding

Some mathematics educators take the constructivist approach when it comes to their idea of the perfect classroom. They believe that actively engaging students in learning is the most productive means of teaching. Active learning strategies were incorporated into the Systems of Linear Equations unit in a ninth-grade Math A classroom to show that active learning strategies would motivate and engage students in the learning process, thus resulting in an enhanced understanding of the material. Strategies included a Jigsaw activity, a Carousel activity, tickets-out-the-door and various written expression assignments. Results from an in-class quiz were used as one way to measure student understanding by comparing the results to the previous year, in which active learning strategies were not used. The greatest impact of student understanding was seen through different uses of written expression

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

Free text adversity statements as part of a contextualised admissions process:a qualitative analysis

Abstract Background Medical schools globally are encouraged to widen access and participation for students from less privileged backgrounds. Many strategies have been implemented to address this inequality, but much still needs to be done to ensure fair access for all. In the literature, adverse circumstances include financial issues, poor educational experience and lack of professional-status parents. In order to take account of adverse circumstances faced by applicants, The University of Dundee School of Medicine offers applicants the opportunity to report circumstances which may have resulted in disadvantage. Applicants do this by completing a free text statement, known as an ‘adversity statement’, in addition to the other application information. This study analysed adversity statements submitted by applicants during two admissions cycles. Analysis of content and theme was done to identify the information applicants wished to be taken into consideration, and what range of adverse circumstances individuals reported. Methods This study used a qualitative approach with thematic analysis to categorise the adversity statements. The data was initially analysed to create a coding framework which was then applied to the whole data set. Each coded segment was then analysed for heterogeneity and homogeneity, segments merged into generated themes, or to create sub-themes. Results The data set comprised a total of 384 adversity statements. These showed a wide range of detail involving family, personal health, education and living circumstances. Some circumstances, such as geographical location, have been identified and explored in previous research, while others, such as long term health conditions, have had less attention in the literature. The degree of impact, the length of statement and degree of detail, demonstrated wide variation between submissions. Conclusions This study adds to the debate on best practice in contextual admissions and raises awareness of the range of circumstances and impact applicants wish to be considered. The themes which emerged from the data included family, school, personal health, and geographical location issues. Descriptions of the degree of impact that an adverse circumstance had on educational or other attainment was found to vary substantially from statements indicating minor, impact through to circumstances stated as causing major impact

Single-cell analysis: visualizing pharmaceutical and metabolite uptake in cells with label-free 3D mass spectrometry imaging

Detecting metabolites and parent compound within a cell type is now a priority for pharmaceutical development. In this context, three-dimensional secondary ion mass spectrometry (SIMS) imaging was used to investigate the cellular uptake of the antiarrhythmic agent amiodarone, a phospholipidosis-inducing pharmaceutical compound. The high lateral resolution and 3D imaging capabilities of SIMS combined with the multiplex capabilities of ToF mass spectrometric detection allows for the visualization of pharmaceutical compound and metabolites in single cells. The intact, unlabeled drug compound was successfully detected at therapeutic dosages in macrophages (cell line: NR8383). Chemical information from endogenous biomolecules was used to correlate drug distributions with morphological features. From this spatial analysis, amiodarone was detected throughout the cell with the majority of the compound found in the membrane and subsurface regions and absent in the nuclear regions. Similar results were obtained when the macrophages were doped with amiodarone metabolite, desethylamiodarone. The FWHM lateral resolution measured across an intracellular interface in a high lateral resolution ion images was approximately 550 nm. Overall, this approach provides the basis for studying cellular uptake of pharmaceutical compounds and their metabolites on the single cell level

The global palm oil sector must change to save biodiversity and improve food security in the tropics

Most palm oil currently available in global markets is sourced from certified large-scale plantations. Comparatively little is sourced from (typically uncertified) smallholders. We argue that sourcing sustainable palm oil should not be determined by commercial certification alone and that the certification process should be revisited. There are so-far unrecognized benefits of sourcing palm oil from smallholders that should be considered if genuine biodiversity conservation is to be a foundation of 'environmentally sustainable' palm oil production. Despite a lack of certification, smallholder production is often more biodiversity-friendly than certified production from large-scale plantations. Sourcing palm oil from smallholders also alleviates poverty among rural farmers, promoting better conservation outcomes. Yet, certification schemes - the current measure of 'sustainability' - are financially accessible only for large-scale plantations that operate as profit-driven monocultures. Industrial palm oil is expanding rapidly in regions with weak environmental laws and enforcement. This warrants the development of an alternative certification scheme for smallholders. Greater attention should be directed to deforestation-free palm oil production in smallholdings, where production is less likely to cause large scale biodiversity loss. These small-scale farmlands in which palm oil is mixed with other crops should be considered by retailers and consumers who are interested in promoting sustainable palm oil production. Simultaneously, plantation companies should be required to make their existing production landscapes more compatible with enhanced biodiversity conservation