No abstract

Background Deakin’s Rural Community Clinical School (RCCS) is a Longitudinal Integrated Clerkship (LIC) program in Western Victoria. Students undertake a year-long placement in a rural General Practice, many of which also host General Practice Registrars. There is a lack of evidence addressing the role and impact of Vertically Integrated Learning (VI) in practices hosting both LIC medical students and General Practice Registrars. The objective of the study was to establish how VI is perceived in the LIC context and the impact that it has on both learners and practices, in order to consider how to potentiate the role it can play in facilitating learning. Methods Semi-structured, in-depth, qualitative interviews were undertaken, with 15 participants located in RCCS General Practices. Emergent themes were identified by thematic analysis. Results Five main interconnected themes were identified; (i) understanding and structure, (ii) planning and evaluation, (iii) benefits, (iv) facilitators, and (v) barriers. Conclusion VI in a rural LIC is not clearly understood, even by participants. VI structure and methodology varied considerably between practices. Benefits included satisfying and efficient sharing of knowledge between learners at different levels. VI was facilitated by the supportive and collegiate environment identified as being present in a rural LIC context. Resources for VI are needed to guide content and expectations across the continuum of medical training and evaluate its role. The financial impact of VI in a rural LIC warrants further exploration.

BackgroundThe A Disintegrin-like and Metalloproteinase domain with Thrombospondin-1 motifs (ADAMTS) enzymes comprise 19 mammalian zinc-dependent metalloproteinases (metzincins) with homologues in a wide range of invertebrates. ADAMTS enzymes have a broad range of functions in development and diseases due to their extracellular matrix remodelling activity. Here, we report a detailed characterisation of their evolutionary conservation across vertebrates.ResultsUsing bioinformatics complemented with de novo sequencing, gene sequences for ADAMTS enzymes were obtained from a variety of organisms. Detailed evolutionary analyses revealed a high level of conservation across vertebrates with evidence of ADAMTS gene expansion during two rounds of whole genome duplication (WGD) in vertebrates, while tandem duplication events and gene loss were also apparent. However, the additional round of teleost-specific WGD did not have a significant effect on ADAMTS gene family members suggesting their conserved roles have remained constant in teleost fish. Quantitative reverse-transcriptase polymerase chain reaction analysis revealed dynamic expression of adamts genes throughout zebrafish embryonic development reflecting the key conserved roles they play in vertebrate embryogenesis. Notably, several adamts mRNAs were maternally expressed with a dramatic increase in mRNA levels coinciding with zygotic expression and organogenesis. Broad adamts mRNA expression was also demonstrated in several adult organs indicating potential roles in adult homeostasis.ConclusionsOur data highlight the evolution of the ADAMTS gene family through duplication processes across metazoans supplemented by a burst of amplification through vertebrate WGD events. It also strongly posits the zebrafish as a potential model species to further elucidate the function of ADAMTS enzymes during vertebrate development.Electronic supplementary materialThe online version of this article (doi:10.1186/s12862-015-0281-9) contains supplementary material, which is available to authorized users.

ObjectivesPatient involvement in safety improvement is a developing area of research. The aim of this study was to investigate the feasibility of a patient feedback on safety intervention in primary care. Specifically, the intervention acceptability, fidelity, implementation enablers and barriers, scalability, and process of systematically collecting safety data were examined.Design, setting and participantsMixed-methods feasibility trial with six purposively selected Australian primary care practices.InterventionThe intervention comprised an iterative process with a cycle of measurement, learning, feedback, action planning and implementation period of 6 months.Primary and secondary outcomesQualitative and quantitative data relating to feasibility measures (acceptability, fidelity, enablers, barriers, scalability and process of collecting safety data) were collected and analysed.ResultsA total of n=1750 patients provided feedback on safety. There was a statistically significant increase in mean patient safety scores indicating improved safety (4.30–4.37, p=0.002). Staff deemed the intervention acceptable, with minor recommendations for improvement. Intervention fidelity was high and implementation enablers were attributed to the intervention structure and framework, use of intuitive problem-solving approaches, and multidisciplinary team involvement. Practice-based safety interventions resulted in sustainable and measurable changes to systems for safety, such as increased access to care and improved patient information accuracy.ConclusionsThe findings indicate that this innovative patient feedback on safety intervention is feasible for scale-up to a larger effectiveness trial and further spread into policy and practice. This intervention complements existing safety improvement strategies and activities, and integrates into current patient feedback service requirements for Australian primary care. Further research is needed to examine the intervention effects on safety incident reduction.

Extracellular matrix remodeling has emerged as an important factor in many cancers. Proteoglycans, including versican (VCAN), are regulated via cleavage by the proteolytic actions of A Disintegrin-like And Metalloproteinase domain with Thrombospondin-1 motif (ADAMTS) family members. Alterations in the balance between Proteoglycans and ADAMTS enzymes have been proposed to contribute to cancer progression. Here, we analyzed the expression of ADAMTS-15 in human prostate cancer, and investigated the effects of enforced expression in prostate cancer cell lines. ADAMTS-15 was found to be expressed in human prostate cancer biopsies with evidence of co-localization with VCAN and its bioactive cleavage fragment versikine. Enforced expression of ADAMTS-15, but not a catalytically-inactive version, decreased cell proliferation and migration of the ‘castrate-resistant’ PC3 prostate cancer cell line in vitro, with survival increased. Analysis of ‘androgen-responsive’ LNCaP prostate cancer cells in vivo in NOD/SCID mice revealed that ADAMTS-15 expression caused slower growing tumors, which resulted in increased survival. This was not observed in castrated mice or with cells expressing catalytically-inactive ADAMTS-15. Collectively, this research identifies the enzymatic function of ADAMTS-15 as having a tumor suppressor role in prostate cancer, possibly in concert with androgens, and that VCAN represents a likely key substrate, highlighting potential new options for the clinic.