University tuition fee increases: the influence of increasing fees on students entering Higher Education; student and staff expectations; and the potential revolution in the culture of Higher Education. A case study within an English post 1992 University

September 2012 English universities witnessed a near trebling of their tuition fees for full-time undergraduate courses to an average of £8,580 per year (UCAS, 2012). In the same period was the growing accountability for universities to publish and demonstrate their performance to students. The research was undertaken in 2012/13 allowing comparison of the students who began their studies on the increased tuition fees, and the students who had started their studies in the previous year and who continued to pay the lower rate of fees. The research was undertaken across two English institutions: one ‘post 1992’ University, and one Further Education (FE) college which offered degree awards. The research includes survey responses from nearly 700 students, 97 academics and five interviews with senior university staff. The study provides evidence that students choose to study to improve their future earnings, seen in the motivating factors on choosing their university. Students taking on the persona of consumers is reflected in the expected rises in standards and reported rises in institutional complaints. Both academics and students expect change within the higher education industry and in institutional cultures. In turn these have implications for developing policy and future research

18F-FDG-PET/MR imaging to monitor disease activity in large vessel vasculitis

Disease-monitoring in large vessel vasculitis (LVV) is challenging. Simultaneous 18F-fluorodeoxyglucose positron emission tomography with magnetic resonance imaging (PET/MRI) provides functional assessment of vascular inflammation alongside high-definition structural imaging with a relatively low burden of radiation exposure. Here, we investigate the ability of PET/MRI to monitor LVV disease activity longitudinally in a prospective cohort of patients with active LVV. We demonstrate that both the PET and MRI components of the scan can distinguish active from inactive disease using established quantification methods. Using logistic-regression modelling of PET/MRI metrics, we devise a novel PET/MRI-specific Vasculitis Activity using MR PET (VAMP) score which is able to distinguish active from inactive disease with more accuracy than established methods and detects changes in disease activity longitudinally. These findings are evaluated in an independent validation cohort. Finally, PET/MRI improves clinicians’ assessment of LVV disease activity and confidence in disease management, as assessed via clinician survey. In summary, PET/MRI may be useful in tracking disease activity and assessing treatment-response in LVV. Based on our findings, larger, prospective studies assessing PET/MRI in LVV are now warranted

Abiraterone acetate plus prednisolone for metastatic patients starting hormone therapy: 5-year follow-up results from the STAMPEDE randomised trial (NCT00268476)

Abiraterone acetate plus prednisolone (AAP) previously demonstrated improved survival in STAMPEDE, a multiarm, multistage platform trial in men starting long-term hormone therapy for prostate cancer. This long-term analysis in metastatic patients was planned for 3 years after the first results. Standard-of-care (SOC) was androgen deprivation therapy. The comparison randomised patients 1:1 to SOC-alone with or without daily abiraterone acetate 1000 mg + prednisolone 5 mg (SOC + AAP), continued until disease progression. The primary outcome measure was overall survival. Metastatic disease risk group was classified retrospectively using baseline CT and bone scans by central radiological review and pathology reports. Analyses used Cox proportional hazards and flexible parametric models, accounting for baseline stratification factors. One thousand and three patients were contemporaneously randomised (November 2011 to January 2014): median age 67 years; 94% newly-diagnosed; metastatic disease risk group: 48% high, 44% low, 8% unassessable; median PSA 97 ng/mL. At 6.1 years median follow-up, 329 SOC-alone deaths (118 low-risk, 178 high-risk) and 244 SOC + AAP deaths (75 low-risk, 145 high-risk) were reported. Adjusted HR = 0.60 (95% CI: 0.50-0.71; P = 0.31 × 10−9) favoured SOC + AAP, with 5-years survival improved from 41% SOC-alone to 60% SOC + AAP. This was similar in low-risk (HR = 0.55; 95% CI: 0.41-0.76) and high-risk (HR = 0.54; 95% CI: 0.43-0.69) patients. Median and current maximum time on SOC + AAP was 2.4 and 8.1 years. Toxicity at 4 years postrandomisation was similar, with 16% patients in each group reporting grade 3 or higher toxicity. A sustained and substantial improvement in overall survival of all metastatic prostate cancer patients was achieved with SOC + abiraterone acetate + prednisolone, irrespective of metastatic disease risk group

Early Ultrasound Surveillance of Newly-Created Hemodialysis Arteriovenous Fistula

Introduction: We assess if ultrasound surveillance of newly-created arteriovenous fistulas (AVFs) can predict nonmaturation sufficiently reliably to justify randomised controlled trial (RCT) evaluation of ultrasounddirected salvage intervention. Methods: Consenting adults underwent blinded fortnightly ultrasound scanning of their AVF after creation, with scan characteristics that predicted AVF non-maturation identified by logistic regression modelling. Results: Of 333 AVFs created, 65.8% matured by 10 weeks. Serial scanning revealed that maturation occurred rapidly, whereas consistently lower fistula flow rates and venous diameters were observed in those that did not mature. Wrist and elbow AVF non-maturation could be optimally modelled from the week four ultrasound parameters alone, but with only moderate positive predictive values (wrist, 60.6% (95% CI 43.9 – 77.3); elbow, 66.7% (48.9 - 84.4)). Moreover, 40 (70.2%) of the 57 AVFs that thrombosed by week 10 had already failed by the week 4 scan, thus limiting the potential of salvage procedures initiated by that scan’s findings to alter overall maturation rates. Modelling of the early ultrasound characteristics could also predict primary patency failure at 6 months, but that model performed poorly at predicting assisted primary failure (those AVFs that failed despite a salvage attempt), partly because patency of at-risk AVFs was maintained by successful salvage performed without recourse to the early scan data. Conclusions: Early ultrasound surveillance may predict fistula maturation, but is likely, at best, to result in only very modest improvements in fistula patency. Power calculations suggest that an impractically large number of participants (>1700) would be required for formal RCT evaluation

Early ultrasound surveillance of newly-created haemodialysis arteriovenous fistula

IntroductionWe assess if ultrasound surveillance of newly-created arteriovenous fistulas (AVFs) can predict nonmaturation sufficiently reliably to justify randomized controlled trial (RCT) evaluation of ultrasound-directed salvage intervention.MethodsConsenting adults underwent blinded fortnightly ultrasound scanning of their AVF after creation, with scan characteristics that predicted AVF nonmaturation identified by logistic regression modeling.ResultsOf 333 AVFs created, 65.8% matured by 10 weeks. Serial scanning revealed that maturation occurred rapidly, whereas consistently lower fistula flow rates and venous diameters were observed in those that did not mature. Wrist and elbow AVF nonmaturation could be optimally modeled from week 4 ultrasound parameters alone, but with only moderate positive predictive values (PPVs) (wrist, 60.6% [95% confidence interval, CI: 43.9–77.3]; elbow, 66.7% [48.9–84.4]). Moreover, 40 (70.2%) of the 57 AVFs that thrombosed by week 10 had already failed by the week 4 scan, thus limiting the potential of salvage procedures initiated by that scan’s findings to alter overall maturation rates. Modeling of the early ultrasound characteristics could also predict primary patency failure at 6 months; however, that model performed poorly at predicting assisted primary failure (those AVFs that failed despite a salvage attempt), partly because patency of at-risk AVFs was maintained by successful salvage performed without recourse to the early scan data.ConclusionEarly ultrasound surveillance may predict fistula maturation, but is likely, at best, to result in only very modest improvements in fistula patency. Power calculations suggest that an impractically large number of participants (>1700) would be required for formal RCT evaluation

Puritans, visionaries and survivors

All readings take place in the here-and-now, even of texts written back there and then. Nowhere in management and organization theory has this been truer of anyone than Max Weber. Unread in English during his lifetime, it was nearly 30 years after his death before his ideas had much impact. When they did, they were read in a context and tradition years away from those in which they were conceived. And, ever since, they have been subject to systematic reinterpretation on the one hand and neglect on the other. The paper addresses how one might use Weber today, in terms of his sensitivity to current issues, such as sustainability, as well as the still largely unacknowledged foundation that Weber constructed for contemporary cultural studies. The paper will bring these two themes together, using analysis of contemporary equivalents to the popular culture that formed the basis for some of Weber's own investigations. Copyright © 2005 SAGE Publications

Deciphering colorectal cancer genetics through multi-omic analysis of 100,204 cases and 154,587 controls of European and east Asian ancestries

In the version of this article initially published, the author affiliations incorrectly listed “Candiolo Cancer Institute FPO-IRCCS, Candiolo (TO), Italy” as “Candiolo Cancer Institute, Candiolo, Italy.” The change has been made to the HTML and PDF versions of the article

Genetic fine mapping and genomic annotation defines causal mechanisms at type 2 diabetes susceptibility loci.

We performed fine mapping of 39 established type 2 diabetes (T2D) loci in 27,206 cases and 57,574 controls of European ancestry. We identified 49 distinct association signals at these loci, including five mapping in or near KCNQ1. 'Credible sets' of the variants most likely to drive each distinct signal mapped predominantly to noncoding sequence, implying that association with T2D is mediated through gene regulation. Credible set variants were enriched for overlap with FOXA2 chromatin immunoprecipitation binding sites in human islet and liver cells, including at MTNR1B, where fine mapping implicated rs10830963 as driving T2D association. We confirmed that the T2D risk allele for this SNP increases FOXA2-bound enhancer activity in islet- and liver-derived cells. We observed allele-specific differences in NEUROD1 binding in islet-derived cells, consistent with evidence that the T2D risk allele increases islet MTNR1B expression. Our study demonstrates how integration of genetic and genomic information can define molecular mechanisms through which variants underlying association signals exert their effects on disease

Discovery of common and rare genetic risk variants for colorectal cancer.

To further dissect the genetic architecture of colorectal cancer (CRC), we performed whole-genome sequencing of 1,439 cases and 720 controls, imputed discovered sequence variants and Haplotype Reference Consortium panel variants into genome-wide association study data, and tested for association in 34,869 cases and 29,051 controls. Findings were followed up in an additional 23,262 cases and 38,296 controls. We discovered a strongly protective 0.3% frequency variant signal at CHD1. In a combined meta-analysis of 125,478 individuals, we identified 40 new independent signals at P < 5 × 10-8, bringing the number of known independent signals for CRC to ~100. New signals implicate lower-frequency variants, Krüppel-like factors, Hedgehog signaling, Hippo-YAP signaling, long noncoding RNAs and somatic drivers, and support a role for immune function. Heritability analyses suggest that CRC risk is highly polygenic, and larger, more comprehensive studies enabling rare variant analysis will improve understanding of biology underlying this risk and influence personalized screening strategies and drug development.Goncalo R Abecasis has received compensation from 23andMe and Helix. He is currently an employee of Regeneron Pharmaceuticals. Heather Hampel performs collaborative research with Ambry Genetics, InVitae Genetics, and Myriad Genetic Laboratories, Inc., is on the scientific advisory board for InVitae Genetics and Genome Medical, and has stock in Genome Medical. Rachel Pearlman has participated in collaborative funded research with Myriad Genetics Laboratories and Invitae Genetics but has no financial competitive interest