Hugh Barr

Abstract Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale 1–3 . Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4–5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter 4 ; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation 5,6 ; analyses timings and patterns of tumour evolution 7 ; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity 8,9 ; and evaluates a range of more-specialized features of cancer genomes 8,10–18 .

BACKGROUND AND REVIEW CONTEXT: Evidence to support the proposition that learning together will help practitioners and agencies work better together remains limited and thinly spread. This review identified, collated, analysed and synthesised the best available contemporary evidence from 21 of the strongest evaluations of IPE to inform the above proposition. In this way we sought to help shape future interprofessional education and maximize the potential for interprofessional learning to contribute to collaborative practice and better care. OBJECTIVES OF THE REVIEW: To identify and review the strongest evaluations of IPE. To classify the outcomes of IPE and note the influence of context on particular outcomes. To develop a narrative about the mechanisms that underpin and inform positive and negative outcomes of IPE. SEARCH STRATEGY: Bibliographic database searches as follows: Medline 1966-2003, CINAHL 1982-2001, BEI 1964-2001, ASSIA 1990-2003 which produced 10,495 abstracts. Subsequently, 884 full papers were obtained and scrutinized. In addition, hand searching (2003-5 issues) of 21 journals known to have published two or more higher quality studies from a previous review. TOPIC DEFINITION AND INCLUSION CRITERIA: Peer-reviewed papers and reports included in the review had to be formal educational initiatives attended by at least two of the many professional groups from health and social care, with the objective of improving care; and learning with, from and about each other. DATA COLLECTION, ANALYSIS AND SYNTHESIS: Standard systematic review procedures were applied for sifting abstracts, scrutinizing full papers and abstracting data. Two members of the team checked each abstract to decide whether the full paper should be read. A third member was consulted over any discrepancies. Similarly, each full paper was read by at least two members of the team and agreement sought before passing it to one member of the team (SR) for data abstraction. Other members of the team checked 10% of the abstraction records. Coding into a Statistical Package for Social Scientists (SPSS) data base led to collection of different outcome measures used in the primary studies via the common metric of an adapted Kirkpatrick's four-level model of educational outcomes. Additionally, a narrative synthesis was built after analysis of primary data with the 3-P model (presage-process-product) of education development and delivery. HEADLINE RESULTS: Government calls for enhanced collaboration amongst practitioners frequently leads to IPE that is then developed and delivered by educators, practitioners or service managers. Staff development is a key influence on the effectiveness of IPE for learners who all have unique values about themselves and others. Authenticity and customization of IPE are important mechanisms for positive outcomes of IPE. Interprofessional education is generally well received, enabling knowledge and skills necessary for collaborative working to be learnt; it is less able to positively influence attitudes and perceptions towards others in the service delivery team. In the context of quality improvement initiatives interprofessional education is frequently used as a mechanism to enhance the development of practice and improvement of services.

BACKGROUND: Interprofessional education (IPE) aims to bring together different professionals to learn with, from, and about one another in order to collaborate more effectively in the delivery of safe, high-quality care for patients/clients. Given its potential for improving collaboration and care delivery, there have been repeated calls for the wider-scale implementation of IPE across education and clinical settings. Increasingly, a range of IPE initiatives are being implemented and evaluated which are adding to the growth of evidence for this form of education. AIM: The overall aim of this review is to update a previous BEME review published in 2007. In doing so, this update sought to synthesize the evolving nature of the IPE evidence. METHODS: Medline, CINAHL, BEI, and ASSIA were searched from May 2005 to June 2014. Also, journal hand searches were undertaken. All potential abstracts and papers were screened by pairs of reviewers to determine inclusion. All included papers were assessed for methodological quality and those deemed as "high quality" were included. The presage-process-product (3P) model and a modified Kirkpatrick model were employed to analyze and synthesize the included studies. RESULTS: Twenty-five new IPE studies were included in this update. These studies were added to the 21 studies from the previous review to form a complete data set of 46 high-quality IPE studies. In relation to the 3P model, overall the updated review found that most of the presage and process factors identified from the previous review were further supported in the newer studies. In regard to the products (outcomes) reported, the results from this review continue to show far more positive than neutral or mixed outcomes reported in the included studies. Based on the modified Kirkpatrick model, the included studies suggest that learners respond well to IPE, their attitudes and perceptions of one another improve, and they report increases in collaborative knowledge and skills. There is more limited, but growing, evidence related to changes in behavior, organizational practice, and benefits to patients/clients. CONCLUSIONS: This updated review found that key context (presage) and process factors reported in the previous review continue to have resonance on the delivery of IPE. In addition, the newer studies have provided further evidence for the effects on IPE related to a number of different outcomes. Based on these conclusions, a series of key implications for the development of IPE are offered.

There is a real need for improvements in cancer detection. Significant problems are encountered when utilising the gold standard of excisional biopsy combined with histopathology. This can include missed lesions, perforation and high levels of inter- and intra-observer discrepancies. The clinical requirements for an objective, non-invasive real time probe for accurate and repeatable measurement of tissue pathological state are overwhelming. This study has evaluated the potential for Raman spectroscopy to achieve this goal. The technique measures the molecular specific inelastic scattering of laser light within tissue, thus enabling the analysis of biochemical changes that precede and accompany disease processes. Initial work has been carried out to optimise a commercially available Raman microspectrometer for tissue measurements; to target potential malignancies with a clinical need for diagnostic improvements (oesophagus. colon, breast, andd prostate) and to build and test spectral libraries and prediction algorithms for tissue types and pathologies. This study has followed rigorous sample collection protocols and histopathological analysis using a board of expert pathologists. Only the data from samples with full agreement of a homogeneous pathology have been used to construct a training data set of Raman spectra. Measurements of tissue specimens from the full spectrum of different pathological groups found in each tissue have been made. Diagnostic predictive models have been constructed and optimised using multivariate analysis techniques. They have been tested using cross-validation or leave-one-out and demonstrated high levels of discrimination between pathology groups (greater than 90% sensitivity and specificity for all tissues). However larger sample numbers are required for further evaluation. The discussions outline the likely work required for successful implementation of in vivo Raman detection of early malignancies.