‘You certainly don’t get promoted for just teaching’:experiences of education-focused academics in research-intensive universities

Changes in drivers of academic roles within higher education institutions globally have resulted in increased proportions of academics in education focused (EF) posts. International and UK research suggests that EF academics can experience dissatisfaction with career progression and the perceived value of their work, including those in research-intensive universities. Previous UK research was conducted prior to the introduction of the TEF which has altered the landscape. Therefore, it was timely to examine the current experience of EF academics in research-intensive universities through a theoretical lens to understand barriers and facilitators to career progression. This interview-based study used two theoretical frameworks, Feldman and Ng’s Framework for Career Mobility, Embeddedness, and Success and Kanter’s theory of Power within organisations to explore the experiences of 43 EF academics across 12 research-intensive UK universities. Four contract types were identified, some of which allowed promotion. Three broad themes were derived from the data, including (1) Lack of agreement on the definition of education-focused academic roles, (2) Level of value and appreciation of educational expertise and the impact on education-focused academics, (3) Career development opportunities for education-focused academics. Recommendations to further enhance the experience and career progression for EF academics in research-intensive universities further include; ensuring transparency in recruitment into EF posts as to whether career development is possible within that post, the need to continue the sector-wide discussion on the definition of EF roles that recognises the complexity and diversity of activity and continued work to value and recognise appropriately educational expertise.</p

A Discussion of Value Metrics for Data Repositories in Earth and Environmental Sciences

Despite growing recognition of the importance of public data to the modern economy and to scientific progress, long-term investment in the repositories that manage and disseminate scientific data in easily accessible-ways remains elusive. Repositories are asked to demonstrate that there is a net value of their data and services to justify continued funding or attract new funding sources. Here, representatives from a number of environmental and Earth science repositories evaluate approaches for assessing the costs and benefits of publishing scientific data in their repositories, identifying various metrics that repositories typically use to report on the impact and value of their data products and services, plus additional metrics that would be useful but are not typically measured. We rated each metric by (a) the difficulty of implementation by our specific repositories and (b) its importance for value determination. As managers of environmental data repositories, we find that some of the most easily obtainable data-use metrics (such as data downloads and page views) may be less indicative of value than metrics that relate to discoverability and broader use. Other intangible but equally important metrics (e.g., laws or regulations impacted, lives saved, new proposals generated), will require considerable additional research to describe and develop, plus resources to implement at scale. As value can only be determined from the point of view of a stakeholder, it is likely that multiple sets of metrics will be needed, tailored to specific stakeholder needs. Moreover, economically based analyses or the use of specialists in the field are expensive and can happen only as resources permit

Factors Associated with Revision Surgery after Internal Fixation of Hip Fractures

Background: Femoral neck fractures are associated with high rates of revision surgery after management with internal fixation. Using data from the Fixation using Alternative Implants for the Treatment of Hip fractures (FAITH) trial evaluating methods of internal fixation in patients with femoral neck fractures, we investigated associations between baseline and surgical factors and the need for revision surgery to promote healing, relieve pain, treat infection or improve function over 24 months postsurgery. Additionally, we investigated factors associated with (1) hardware removal and (2) implant exchange from cancellous screws (CS) or sliding hip screw (SHS) to total hip arthroplasty, hemiarthroplasty, or another internal fixation device. Methods: We identified 15 potential factors a priori that may be associated with revision surgery, 7 with hardware removal, and 14 with implant exchange. We used multivariable Cox proportional hazards analyses in our investigation. Results: Factors associated with increased risk of revision surgery included: female sex, [hazard ratio (HR) 1.79, 95% confidence interval (CI) 1.25-2.50; P = 0.001], higher body mass index (fo

Adding 6 months of androgen deprivation therapy to postoperative radiotherapy for prostate cancer: a comparison of short-course versus no androgen deprivation therapy in the RADICALS-HD randomised controlled trial

Background Previous evidence indicates that adjuvant, short-course androgen deprivation therapy (ADT) improves metastasis-free survival when given with primary radiotherapy for intermediate-risk and high-risk localised prostate cancer. However, the value of ADT with postoperative radiotherapy after radical prostatectomy is unclear. Methods RADICALS-HD was an international randomised controlled trial to test the efficacy of ADT used in combination with postoperative radiotherapy for prostate cancer. Key eligibility criteria were indication for radiotherapy after radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to radiotherapy alone (no ADT) or radiotherapy with 6 months of ADT (short-course ADT), using monthly subcutaneous gonadotropin-releasing hormone analogue injections, daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as distant metastasis arising from prostate cancer or death from any cause. Standard survival analysis methods were used, accounting for randomisation stratification factors. The trial had 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 80% to 86% (hazard ratio [HR] 0·67). Analyses followed the intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov, NCT00541047. Findings Between Nov 22, 2007, and June 29, 2015, 1480 patients (median age 66 years [IQR 61–69]) were randomly assigned to receive no ADT (n=737) or short-course ADT (n=743) in addition to postoperative radiotherapy at 121 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 9·0 years (IQR 7·1–10·1), metastasis-free survival events were reported for 268 participants (142 in the no ADT group and 126 in the short-course ADT group; HR 0·886 [95% CI 0·688–1·140], p=0·35). 10-year metastasis-free survival was 79·2% (95% CI 75·4–82·5) in the no ADT group and 80·4% (76·6–83·6) in the short-course ADT group. Toxicity of grade 3 or higher was reported for 121 (17%) of 737 participants in the no ADT group and 100 (14%) of 743 in the short-course ADT group (p=0·15), with no treatment-related deaths. Interpretation Metastatic disease is uncommon following postoperative bed radiotherapy after radical prostatectomy. Adding 6 months of ADT to this radiotherapy did not improve metastasis-free survival compared with no ADT. These findings do not support the use of short-course ADT with postoperative radiotherapy in this patient population

Duration of androgen deprivation therapy with postoperative radiotherapy for prostate cancer: a comparison of long-course versus short-course androgen deprivation therapy in the RADICALS-HD randomised trial

Background Previous evidence supports androgen deprivation therapy (ADT) with primary radiotherapy as initial treatment for intermediate-risk and high-risk localised prostate cancer. However, the use and optimal duration of ADT with postoperative radiotherapy after radical prostatectomy remains uncertain. Methods RADICALS-HD was a randomised controlled trial of ADT duration within the RADICALS protocol. Here, we report on the comparison of short-course versus long-course ADT. Key eligibility criteria were indication for radiotherapy after previous radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to add 6 months of ADT (short-course ADT) or 24 months of ADT (long-course ADT) to radiotherapy, using subcutaneous gonadotrophin-releasing hormone analogue (monthly in the short-course ADT group and 3-monthly in the long-course ADT group), daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as metastasis arising from prostate cancer or death from any cause. The comparison had more than 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 75% to 81% (hazard ratio [HR] 0·72). Standard time-to-event analyses were used. Analyses followed intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov , NCT00541047 . Findings Between Jan 30, 2008, and July 7, 2015, 1523 patients (median age 65 years, IQR 60–69) were randomly assigned to receive short-course ADT (n=761) or long-course ADT (n=762) in addition to postoperative radiotherapy at 138 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 8·9 years (7·0–10·0), 313 metastasis-free survival events were reported overall (174 in the short-course ADT group and 139 in the long-course ADT group; HR 0·773 [95% CI 0·612–0·975]; p=0·029). 10-year metastasis-free survival was 71·9% (95% CI 67·6–75·7) in the short-course ADT group and 78·1% (74·2–81·5) in the long-course ADT group. Toxicity of grade 3 or higher was reported for 105 (14%) of 753 participants in the short-course ADT group and 142 (19%) of 757 participants in the long-course ADT group (p=0·025), with no treatment-related deaths. Interpretation Compared with adding 6 months of ADT, adding 24 months of ADT improved metastasis-free survival in people receiving postoperative radiotherapy. For individuals who can accept the additional duration of adverse effects, long-course ADT should be offered with postoperative radiotherapy. Funding Cancer Research UK, UK Research and Innovation (formerly Medical Research Council), and Canadian Cancer Society

‘You certainly don’t get promoted for just teaching’: experiences of education-focused academics in research-intensive universities

Changes in drivers of academic roles within higher education institutions globally have resulted in increased proportions of academics in education focused (EF) posts. International and UK research suggests that EF academics can experience dissatisfaction with career progression and the perceived value of their work, including those in research-intensive universities. Previous UK research was conducted prior to the introduction of the TEF which has altered the landscape. Therefore, it was timely to examine the current experience of EF academics in research-intensive universities through a theoretical lens to understand barriers and facilitators to career progression. This interview-based study used two theoretical frameworks, Feldman and Ng’s Framework for Career Mobility, Embeddedness, and Success and Kanter’s theory of Power within organisations to explore the experiences of 43 EF academics across 12 research-intensive UK universities. Four contract types were identified, some of which allowed promotion. Three broad themes were derived from the data, including (1) Lack of agreement on the definition of education-focused academic roles, (2) Level of value and appreciation of educational expertise and the impact on education-focused academics, (3) Career development opportunities for education-focused academics. Recommendations to further enhance the experience and career progression for EF academics in research-intensive universities further include; ensuring transparency in recruitment into EF posts as to whether career development is possible within that post, the need to continue the sector-wide discussion on the definition of EF roles that recognises the complexity and diversity of activity and continued work to value and recognise appropriately educational expertise.</p

Discovery of a Novel Mutant-Selective Epidermal Growth Factor Receptor Inhibitor Using in silico Enabled Drug Discovery Platform

Despite the success of first, second and third generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in treatment of non-small cell lung cancer (NSCLC) with classical EGFR mutations (L858R or Exon 19 deletions), disease progression often occurs due to the acquisition of additional mutations in the EGFR kinase domain that confer TKI resistance. Specifically, acquisition of both T790M and C797S resistance mutations results in an EGFR variant that is resistant to all approved EGFR TKIs. Herein, we report a physics-based computationally-driven lead identification approach which successfully identified structurally-unique imidazo[3.2-b]pyrazole derivatives as reversible inhibitors of EGFR classical mutations bearing both T790M and C797S. Importantly, they spare EGFR WT to avoid known EGFR WT-driven cutaneous toxicities. During profiling of imidazo[3.2-b]pyrazole derivatives, we elucidated the bioactivation mechanism causing CYP3A4/5 time-dependent inhibition (TDI) and found key modifications to suppress bioactivation and mitigate the TDI risk. Representative lead compound 31 inhibited EGFR L858R/T790M/C797S in biochemical assays with a Ki = 2.1 nM, and EGFR del19/T790M/C797S in a Ba/F3 cellular assay with a IC50 = 56.9 nM. Deuterated analog of 31 (38) demonstrated dose-dependent tumor growth inhibition in a Ba/F3 EGFR del19/T790M/C797S CDX model by 47% at 50 mg/kg BID and 92% at 100 mg/kg BID