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Background Biomedical Research Centres (BRCs) are partnerships between healthcare organisations and universities in England. Their mission is to generate novel treatments, technologies, diagnostics and other interventions that increase the country’s international competitiveness, to rapidly translate these innovations into benefits for patients, and to improve efficiency and reduce waste in healthcare. As NIHR Oxford BRC (Oxford BRC) enters its third 5-year funding period, we seek to (1) apply the evidence base on how best to support the various partnerships in this large, multi-stakeholder research system and (2) research how these partnerships play out in a new, ambitious programme of translational research. Methods Organisational case study, informed by the principles of action research. A cross-cutting theme, ‘Partnerships for Health, Wealth and Innovation’ has been established with multiple sub-themes (drug development, device development, business support and commercialisation, research methodology and statistics, health economics, bioethics, patient and public involvement and engagement, knowledge translation, and education and training) to support individual BRC research themes and generate cross-theme learning. The ‘Partnerships’ theme will support the BRC’s goals by facilitating six types of partnership (with patients and citizens, clinical services, industry, across the NIHR infrastructure, across academic disciplines, and with policymakers and payers) through a range of engagement platforms and activities. We will develop a longitudinal progress narrative centred around exemplar case studies, and apply theoretical models from innovation studies (Triple Helix), sociology of science (Mode 2 knowledge production) and business studies (Value Co-creation). Data sources will be the empirical research studies within individual BRC research themes (who will apply separately for NHS ethics approval), plus documentary analysis and interviews and ethnography with research stakeholders. This study has received ethics clearance through the University of Oxford Central University Research Ethics Committee. Discussion We anticipate that this work will add significant value to Oxford BRC. We predict accelerated knowledge translation; closer alignment of the innovation process with patient priorities and the principles of responsible, ethical research; reduction in research waste; new knowledge about the governance and activities of multi-stakeholder research partnerships and the contexts in which they operate; and capacity-building that reflects the future needs of a rapidly-evolving health research system.

Background Molecular analyses such as whole-genome sequencing have become routine and are expected to be transformational for future healthcare and lifestyle decisions. Population-wide implementation of such analyses is, however, not without challenges, and multiple studies are ongoing to identify what these are and explore how they can be addressed. Methods Defined as a research project, the Personal Genome Project UK (PGP-UK) is part of the global PGP network and focuses on open data sharing and citizen science to advance and accelerate personalized genomics and medicine. Results Here we report our findings on using an open consent recruitment protocol, active participant involvement, open access release of personal genome, methylome and transcriptome data and associated analyses, including 47 new variants predicted to affect gene function and innovative reports based on the analysis of genetic and epigenetic variants. For this pilot study, we recruited 10 participants willing to actively engage as citizen scientists with the project. In addition, we introduce Genome Donation as a novel mechanism for openly sharing previously restricted data and discuss the first three donations received. Lastly, we present GenoME, a free, open-source educational app suitable for the lay public to allow exploration of personal genomes. Conclusions Our findings demonstrate that citizen science-based approaches like PGP-UK have an important role to play in the public awareness, acceptance and implementation of genomics and personalized medicine.

Molecular analyses such as whole-genome sequencing have become routine and are expected to be transformational for future healthcare and lifestyle decisions. Population-wide implementation of such analyses is, however, not without challenges, and multiple studies are ongoing to identify what these are and explore how they can be addressed. Defined as a research project, the Personal Genome Project UK (PGP-UK) is part of the global PGP network and focuses on open data sharing and citizen science to advance and accelerate personalized genomics and medicine. Here we report our findings on using an open consent recruitment protocol, active participant involvement, open access release of personal genome, methylome and transcriptome data and associated analyses, including 47 new variants predicted to affect gene function and innovative reports based on the analysis of genetic and epigenetic variants. For this pilot study, we recruited ten participants willing to actively engage as citizen scientists with the project. In addition, we introduce Genome Donation as a novel mechanism for openly sharing previously restricted data and discuss the first three donations received. Lastly, we present GenoME, a free, open-source educational app suitable for the lay public to allow exploration of personal genomes. Our findings demonstrate that citizen science-based approaches like PGP-UK have an important role to play in the public awareness, acceptance and implementation of genomics and personalized medicine.

Genome-wide association studies (GWAS) of colorectal cancer (CRC) have identified 23 susceptibility loci thus far. Analyses of previously conducted GWAS indicate additional risk loci are yet to be discovered. To identify novel CRC susceptibility loci, we conducted a new GWAS and performed a meta-analysis with five published GWAS (totalling 7,577 cases and 9,979 controls of European ancestry), imputing genotypes utilising the 1000 Genomes Project. The combined analysis identified new, significant associations with CRC at 1p36.2 marked by rs72647484 (minor allele frequency [MAF] = 0.09) near CDC42 and WNT4 ( P  = 1.21 × 10 −8 , odds ratio [OR] = 1.21 ) and at 16q24.1 marked by rs16941835 (MAF = 0.21, P  = 5.06 × 10 −8 ; OR = 1.15) within the long non-coding RNA (lncRNA) RP11-58A18.1 and ~500 kb from the nearest coding gene FOXL1 . Additionally we identified a promising association at 10p13 with rs10904849 intronic to CUBN (MAF = 0.32, P  = 7.01 × 10 -8 ; OR = 1.14). These findings provide further insights into the genetic and biological basis of inherited genetic susceptibility to CRC. Additionally, our analysis further demonstrates that imputation can be used to exploit GWAS data to identify novel disease-causing variants.

Objective Colorectal cancer (CRC) has a substantial heritable component. Common genetic variation has been shown to contribute to CRC risk. A study was conducted in a large multi-population study to assess the feasibility of CRC risk prediction using common genetic variant data combined with other risk factors. A risk prediction model was built and applied to the Scottish population using available data. Design Nine populations of European descent were studied to develop and validate CRC risk prediction models. Binary logistic regression was used to assess the combined effect of age, gender, family history (FH) and genotypes at 10 susceptibility loci that individually only modestly influence CRC risk. Risk models were generated from case-control data incorporating genotypes alone (n=39 266) and in combination with gender, age and FH (n=11 324). Model discriminatory performance was assessed using 10-fold internal cross-validation and externally using 4187 independent samples. The 10-year absolute risk was estimated by modelling genotype and FH with age- and gender-specific population risks. Results The median number of risk alleles was greater in cases than controls (10 vs 9, p<2.2×10−16), confirmed in external validation sets (Sweden p=1.2×10−6, Finland p=2×10−5). The mean per-allele increase in risk was 9% (OR 1.09; 95% CI 1.05 to 1.13). Discriminative performance was poor across the risk spectrum (area under curve for genotypes alone 0.57; area under curve for genotype/age/gender/FH 0.59). However, modelling genotype data, FH, age and gender with Scottish population data shows the practicalities of identifying a subgroup with >5% predicted 10-year absolute risk. Conclusion Genotype data provide additional information that complements age, gender and FH as risk factors, but individualised genetic risk prediction is not currently feasible. Nonetheless, the modelling exercise suggests public health potential since it is possible to stratify the population into CRC risk categories, thereby informing targeted prevention and surveillance.

Background: Observational studies have associated adiposity with an increased risk of colorectal cancer (CRC). However, such studies do not establish a causal relationship. To minimise bias from confounding we performed a Mendelian randomisation (MR) analysis to examine the relationship between adiposity and CRC. Methods: We used SNPs associated with adult body mass index (BMI), waist-hip ratio (WHR), childhood obesity and birth weight as instrumental variables in a MR analysis of 9254 CRC cases and 18 386 controls. Results: In the MR analysis, the odds ratios (ORs) of CRC risk per unit increase in BMI, WHR and childhood obesity were 1.23 (95% CI: 1.02–1.49, P =0.033), 1.59 (95% CI: 1.08–2.34, P =0.019) and 1.07 (95% CI: 1.03–1.13, P =0.018), respectively. There was no evidence for association between birth weight and CRC (OR=1.22, 95% CI: 0.89–1.67, P =0.22). Combining these data with a concurrent MR-based analysis for BMI and WHR with CRC risk (totalling to 18 190 cases, 27 617 controls) provided increased support, ORs for BMI and WHR were 1.26 (95% CI: 1.10–1.44, P =7.7 × 10 −4 ) and 1.40 (95% CI: 1.14–1.72, P =1.2 × 10 −3 ), respectively. Conclusions: These data provide further evidence for a strong causal relationship between adiposity and the risk of developing CRC highlighting the urgent need for prevention and treatment of adiposity.

Over the last four years, ORCHID (the Centre for Outcomes and Experience Research in Children’s Health, Illness and Disability) at GOSH has had great success in supporting nurses, allied health professionals (AHPs) and a junior doctor to apply for clinical academic funding from a range of highly competitive schemes, including the National Institute of Health Research (NIHR). This support has included the running of an internship programme funded by the GOSH NIHR BRC, regular teaching, and knowledgeable and supportive academic supervisors. This has enabled each clinician to lead on research and make valuable contributions to patient care in their specialist fields.The process for individuals undertaking a PhD can be a challenging, and often lonely experience. The transition from expert clinician to novice researcher can be a shock. An important way to alleviate some of these challenges is to surround oneself with people who are enabling and supportive.Peer-support has proved to be an invaluable source of support for this growing group of multi-disciplinary researchers. This diverse group, made up of a dietician, family therapist, junior doctor, nurses, physiotherapists, radiographer, speech and language specialist, occupational therapist and an orthoptist, has created a WhatsApp group, held virtual and in-person, social evenings and discussion forums to allow the sharing of positive and negative experiences, dissemination of practical tips and provision of moral support. The group has created a non-threatening, respectful, safe environment and welcomes all clinical academics embarking on a PhD.This network of engaged, expert and motivated professionals is key to delivering world-leading patient outcomes and developing the GOSH research leaders of the future. Ensuring their success, using the peer support described, will help support the Trust’s aim of establishing a formal clinical academic career pathway for nurses and AHPs, as part of it becoming a research hospital.

This paper explores the concept of career communities: social structures that provide career support and frequently transcend the boundaries of any single organization. The theoretical background notes the convergence of a number of different perspectives from both career development and organization studies, pertaining to the social contextualization of careers. The methodology involved eliciting expressions of the (individual) subjective career from the members of three potential career communities, and then exploring (communal) inter-subjective interpretations in focus groups. Our results suggest that career communities typically involve a hybrid of types rather than any one pure type. Preliminary support is found for the view that career communities facilitate career support, sensemaking and learning. The results invite further research into career communities and have implications for organizational behavior and human resource management, suggesting greater appreciation of the extra-organizational as well as intra-organizational communities in which careers develop.

Genome-wide association studies (GWAS) of colorectal cancer (CRC) have identified 23 susceptibility loci thus far. Analyses of previously conducted GWAS indicate additional risk loci are yet to be discovered. To identify novel CRC susceptibility loci, we conducted a new GWAS and performed a meta-analysis with five published GWAS (totalling 7,577 cases and 9,979 controls of European ancestry), imputing genotypes utilising the 1000 Genomes Project. The combined analysis identified new, significant associations with CRC at 1p36.2 marked by rs72647484 (minor allele frequency [MAF]  =  0.09) near CDC42 and WNT4 ( P   =  1.21  ×  10 −8 , odds ratio [OR]  =  1.21 ) and at 16q24.1 marked by rs16941835 (MAF  =  0.21, P   =  5.06  ×  10 −8 ; OR  =  1.15) within the long non-coding RNA (lncRNA) RP11-58A18.1 and ~500 kb from the nearest coding gene FOXL1 . Additionally we identified a promising association at 10p13 with rs10904849 intronic to CUBN (MAF = 0.32, P  = 7.01 × 10 -8 ; OR = 1.14). These findings provide further insights into the genetic and biological basis of inherited genetic susceptibility to CRC. Additionally, our analysis further demonstrates that imputation can be used to exploit GWAS data to identify novel disease-causing variants.

This e-book on careers in cross-cultural perspective contributes to the growing body of literature that addresses careers from different locations in the world, including countries far from the mainstream of careers research. It focuses on differences and similarities among careers and career attributes in different cultural and national contexts. The contributions included provide insights into career beliefs in China, Russia, Canada, Argentina and Mexico; social networking for job search in the USA and China; and the dynamic character of career concepts and attributes driven by social, political and economic changes in the various countries.