Search

The world and the workforce are changing with the rise of Industry 4.0, or the Fourth Industrial Revolution, with a shift towards automation and digital technology, and this is coupled with other global shifts such as the climate crisis. Organisations such as the World Economic Forum, the International Labour Organisation, and Skills Development Scotland believe Industry 4.0 will change the way we work and live, with implications for everyone. These organisations argue that we need to become lifelong learners and develop future-ready skills, most notably adaptability, creativity, critical thinking, and problem-solving. But what does this mean for Learning Developers? Firstly, we need to consider how and if our own roles will change, and secondly the impact this will have on our learners and what (if any) changes we should make to support them. I used the following prompt questions to start the discussions: • Should Learning Developers be concerned about Industry 4.0? • What are future-ready skills and are these already embedded in higher education? • Should Industry 4.0 impact the way Learning Developers think about lifelong learning?

Objectives Our aim was to identify which patients are likely to stay in hospital longer following total hip replacement surgery.Design Longitudinal, observational study used routinely collected data.Setting Data were collected from an NHS Trust in South-West England between 2016 and 2019.Participants 2352 hip replacement patients had complete data and were included in analysis.Primary and secondary outcome measures Three measures of length of stay were used: a count measure of number of days spent in hospital, a binary measure of ≤7 days/>7 days in hospital and a binary measure of remaining in hospital when medically fit for discharge.Results The mean length of stay was 5.4 days following surgery, with 18% in hospital for more than 7 days, and 11% staying in hospital when medically fit for discharge. Longer hospital stay was associated with older age (OR=1.06, 95% CI 1.05 to 1.08), being female (OR=1.42, 95% CI 1.12 to 1.81) and more comorbidities (OR=3.52, 95% CI 1.45 to 8.55) and shorter length of stay with not having had a recent hospital admission (OR=0.44, 95% CI 0.32 to 0.60). Results were similar for remaining in hospital when medically fit for discharge, with the addition of an association with highest socioeconomic deprivation (OR=2.08, 95% CI 1.37 to 3.16).Conclusions Older, female patients with more comorbidities and from more socioeconomically deprived areas are likely to remain in hospital for longer following surgery. This study produced regression models demonstrating consistent results across three measures of prolonged hospital stay following hip replacement surgery. These findings could be used to inform surgery planning and when supporting patient discharge following surgery.

Protein kinases act as central molecular switches in the control of cellular functions. Alterations in the regulation and function of protein kinases may provoke diseases including cancer. In this study we investigate the conformational states of such disease-associated kinases using the high sensitivity of the kinase conformation (KinCon) reporter system. We first track BRAF kinase activity conformational changes upon melanoma drug binding. Second, we also use the KinCon reporter technology to examine the impact of regulatory protein interactions on LKB1 kinase tumor suppressor functions. Third, we explore the conformational dynamics of RIP kinases in response to TNF pathway activation and small molecule interactions. Finally, we show that CDK4/6 interactions with regulatory proteins alter conformations which remain unaffected in the presence of clinically applied inhibitors. Apart from its predictive value, the KinCon technology helps to identify cellular factors that impact drug efficacies. The understanding of the structural dynamics of full-length protein kinases when interacting with small molecule inhibitors or regulatory proteins is crucial for designing more effective therapeutic strategies.

Abstract Background Near-real time surveillance of excess mortality has been an essential tool during the COVID-19 pandemic. It remains critical for monitoring mortality as the pandemic wanes, to detect fluctuations in the death rate associated both with the longer-term impact of the pandemic (e.g. infection, containment measures and reduced service provision by the health and other systems) and the responses that followed (e.g. curtailment of containment measures, vaccination and the response of health and other systems to backlogs). Following the relaxing of social distancing regimes and reduction in the availability of testing, across many countries, it becomes critical to measure the impact of COVID-19 infection. However, prolonged periods of mortality in excess of the expected across entire populations has raised doubts over the validity of using unadjusted historic estimates of mortality to calculate the expected numbers of deaths that form the baseline for computing numbers of excess deaths because many individuals died earlier than they would otherwise have done: i.e. their mortality was displaced earlier in time to occur during the pandemic rather than when historic rates predicted. This is also often termed “harvesting” in the literature. Methods We present a novel Cox-regression-based methodology using time-dependent covariates to estimate the profile of the increased risk of death across time in individuals who contracted COVID-19 among a population of hip fracture patients in England (N = 98,365). We use these hazards to simulate a distribution of survival times, in the presence of a COVID-19 positive test, and then calculate survival times based on hazard rates without a positive test and use the difference between the medians of these distributions to estimate the number of days a death has been displaced. This methodology is applied at the individual level, rather than the population level to provide a better understanding of the impact of a positive COVID-19 test on the mortality of groups with different vulnerabilities conferred by sociodemographic and health characteristics. Finally, we apply the mortality displacement estimates to adjust estimates of excess mortality using a “ball and urn” model. Results Among the exemplar population we present an end-to-end application of our methodology to estimate the extent of mortality displacement. A greater proportion of older, male and frailer individuals were subject to significant displacement while the magnitude of displacement was higher in younger females and in individuals with lower frailty: groups who, in the absence of COVID-19, should have had a substantial life expectancy. Conclusion Our results indicate that calculating the expected number of deaths following the first wave of the pandemic in England based solely on historical trends results in an overestimate, and excess mortality will therefore be underestimated. Our findings, using this exemplar dataset are conditional on having experienced a hip fracture, which is not generalisable to the general population. Fractures that impede mobility in the weeks that follow the accident/surgery considerably shorten life expectancy and are in themselves markers of significant frailty. It is therefore important to apply these novel methods to the general population, among whom we anticipate strong patterns in mortality displacement – both in its length and prevalence – by age, sex, frailty and types of comorbidities. This counterfactual method may also be used to investigate a wider range of disruptive population health events. This has important implications for public health monitoring and the interpretation of public health data in England and globally.

Background The place of tonsillectomy in the management of sore throat in adults remains uncertain. Objectives To establish the clinical effectiveness and cost-effectiveness of tonsillectomy, compared with conservative management, for tonsillitis in adults, and to evaluate the impact of alternative sore throat patient pathways. Design This was a multicentre, randomised controlled trial comparing tonsillectomy with conservative management. The trial included a qualitative process evaluation and an economic evaluation. Setting The study took place at 27 NHS secondary care hospitals in Great Britain. Participants A total of 453 eligible participants with recurrent sore throats were recruited to the main trial. Interventions Patients were randomised on a 1 : 1 basis between tonsil dissection and conservative management (i.e. deferred surgery) using a variable block-stratified design, stratified by (1) centre and (2) severity. Main outcome measures The primary outcome measure was the total number of sore throat days over 24 months following randomisation. The secondary outcome measures were the number of sore throat episodes and five characteristics from Sore Throat Alert Return, describing severity of the sore throat, use of medications, time away from usual activities and the Short Form questionnaire-12 items. Additional secondary outcomes were the Tonsil Outcome Inventory-14 total and subscales and Short Form questionnaire-12 items 6 monthly. Evaluation of the impact of alternative sore throat patient pathways by observation and statistical modelling of outcomes against baseline severity, as assessed by Tonsil Outcome Inventory-14 score at recruitment. The incremental cost per sore throat day avoided, the incremental cost per quality-adjusted life-year gained based on responses to the Short Form questionnaire-12 items and the incremental net benefit based on costs and responses to a contingent valuation exercise. A qualitative process evaluation examined acceptability of trial processes and ramdomised arms. Results There was a median of 27 (interquartile range 12–52) sore throats over the 24-month follow-up. A smaller number of sore throats was reported in the tonsillectomy arm [median 23 (interquartile range 11–46)] than in the conservative management arm [median 30 (interquartile range 14–65)]. On an intention-to-treat basis, there were fewer sore throats in the tonsillectomy arm (incident rate ratio 0.53, 95% confidence interval 0.43 to 0.65). Sensitivity analyses confirmed this, as did the secondary outcomes. There were 52 episodes of post-operative haemorrhage reported in 231 participants undergoing tonsillectomy (22.5%). There were 47 re-admissions following tonsillectomy (20.3%), 35 relating to haemorrhage. On average, tonsillectomy was more costly and more effective in terms of both sore throat days avoided and quality-adjusted life-years gained. Tonsillectomy had a 100% probability of being considered cost-effective if the threshold for an additional quality-adjusted life year was £20,000. Tonsillectomy had a 69% probability of having a higher net benefit than conservative management. Trial processes were deemed to be acceptable. Patients who received surgery were unanimous in reporting to be happy to have received it. Limitations The decliners who provided data tended to have higher Tonsillectomy Outcome Inventory-14 scores than those willing to be randomised implying that patients with a higher burden of tonsillitis symptoms may have declined entry into the trial. Conclusions The tonsillectomy arm had fewer sore throat days over 24 months than the conservative management arm, and had a high probability of being considered cost-effective over the ranges considered. Further work should focus on when tonsillectomy should be offered. National Trial of Tonsillectomy IN Adults has assessed the effectiveness of tonsillectomy when offered for the current UK threshold of disease burden. Further research is required to define the minimum disease burden at which tonsillectomy becomes clinically effective and cost-effective. Trial registration This trial is registered as ISRCTN55284102. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 12/146/06) and is published in full in Health Technology Assessment; Vol. 27, No. 31. See the NIHR Funding and Awards website for further award information. Plain language summary Tonsillectomy is an operation to take out the pair of tonsil glands at the back of the throat. It is an option for adults who suffer from repeated, severe sore throats. Adults who have a tonsillectomy say that they get fewer sore throats afterwards, but it is not clear whether or not they would have got better over time without the operation. There is pressure on doctors to limit the number of tonsillectomies carried out. At the same time, emergency hospital admissions for adults with severe throat infections have been increasing. NAtional Trial of Tonsillectomy IN Adults aimed to find out whether tonsillectomy is an effective and worthwhile treatment for repeated severe sore throats or whether patients would be better off treated without an operation. A total of 453 patients from 27 hospitals in Great Britain took part in the study. Patients were assigned at random to receive either tonsillectomy or conservative management (treatment as needed from their general practitioner). We measured how many sore throats patients had in the next 2 years by sending them text messages every week. We asked about the impact of their sore throats on their quality of life and time off work, and looked at the costs of treatment. We also interviewed 47 patients, general practitioners and hospital staff about their experiences of tonsillectomy and NAtional Trial of Tonsillectomy IN Adults. The typical patient in the tonsillectomy arm had 23 days of sore throat compared with 30 days of sore throat in the conservative management arm. Tonsillectomy resulted in higher quality of life. We looked to see whether or not it was only those with the most severe sore throats who benefited from tonsillectomy, but we found that patients with more or less severe sore throats at the start all did better with tonsillectomy. Patients who had a tonsillectomy were happy to have undertaken this. Our findings suggest a clear benefit of tonsillectomy using modest additional NHS resources for adults with repeated severe sore throats. Scientific summary Background Sore throats cost the NHS over £120M per annum, including ≈ £60M for general practitioner (GP) consultations and medical therapy. The place of tonsillectomy in the management of sore throat remains uncertain. Objectives Clinical To establish the clinical effectiveness of tonsillectomy, compared with conservative management, for tonsillitis in adults. To report the number of adverse events (AEs), visits to the GP/walk-in clinic/accident and emergency, prescriptions issued and additional interventions required to manage sore throats and related events through weekly Sore Throat Alert Return (STAR) response data and primary care patient records. To adjust the estimate of effectiveness in the light of other baseline covariates, including severity of tonsillitis. To evaluate the impact of alternative sore throat patient pathways by observation and statistical modelling of outcomes. To assess to what extent trial participants were representative of the total population of sore throat patients referred to ear, nose and throat (ENT) clinics. To inform future research. Qualitative process evaluation To examine the acceptability of the trial, treatments and unforeseen consequences from the perspective of participants and stakeholders, including ENT staff and GPs. Economic evaluation To compare costs incurred by the NHS, Personal and Social Services (PSS) and participants to manage recurrent sore throats in adults. To compare quality-adjusted life-years (QALYs) using the area-under-the-curve method based on Short Form questionnaire-6 Dimension (SF-6D) scores derived from longitudinal Short Form questionnaire-12 items (SF-12) responses throughout the study and during self-reported sore throat episodes. To compare the cost-effectiveness measured in terms of the incremental: cost per sore throat day avoided cost per QALY gained net benefit – estimated based on self-reported number of sore throat days and responses to a contingent valuation questionnaire administered at baseline asking participants’ willingness to pay (WTP) to avoid a sore throat day. Methods Design A multicentre, randomised controlled trial comparing the effectiveness of tonsillectomy for recurrent sore throat with that of non-surgical conservative management in a 1 : 1 ratio over a 24-month period. Surgeons, participants and site staff could not be blinded to the allocated procedure. The main trial began following the completion of a feasibility study and included a qualitative process evaluation, as well as an economic evaluation. The design, conduct and reporting of the trial were informed by patients. Crossover of participants between arms was permitted. Interventions Tonsil dissection: dissection of the palatine tonsils preferably within 6 weeks, and no more than 8 weeks, following randomisation (dissection method at the discretion of the participating centres). Conservative (non-surgical) management (i.e. deferred surgery): participants entering the conservative management arm were asked to defer surgery for up to 24 months on the understanding that they would be reviewed at 12 months. Setting and participants A total of 453 patients were recruited to the main trial from 27 NHS secondary care hospitals in Great Britain. Eligible patients were identified via general ENT referrals and established sore throat-specific referral pathways, some of which were run by ENT nurse practitioners. Inclusion criteria Aged ≥16 years. Recurrent sore throats that fulfil current Scottish Intercollegiate Guidelines Network (SIGN) guidance for elective tonsillectomy. Exclusion criteria Previous tonsillectomy. Listed directly (i.e. added to waiting list without prior elective ENT outpatient appointment) during emergency admission (e.g. owing to peritonsillar abscess/quinsy). Primary sleep breathing disorder. Suspected malignancy. Tonsilloliths (as primary referral). Pregnant or breastfeeding. Bleeding diathesis (including haemophilia, sickle cell disease and platelet dysfunction). Therapeutic anticoagulation. Inability to complete self-reported questionnaires and sore throat returns. Main outcome measures Primary outcome The primary outcome measure was the total number of sore throat days over the 24 months following randomisation. The number of sore throat days was collected by a database that was designed for use in the trial (the STAR database). This database allowed participants to respond weekly to alerts by providing the number of sore throats that they had experienced in the previous 7 days (between 0 and 7 sore throat days). From the beginning of the trial, participants were able to choose their preferred method for receiving these alerts: e-mail, text message or interactive voice response (IVR) via telephone. Secondary outcomes A participant who had suffered from a sore throat in the past week (i.e. sore throat days >0) was asked to provide information on the severity of the sore throat(s) and additional data for health economics and other secondary outcomes in a STAR questionnaire. Quality-of-life data, reported as the SF-12 physical component score (PCS) and mental component score (MCS) and additional symptoms of tonsillitis, were collected every 6 months. The impact of alternative NHS sore throat pathways was measured by observation and statistical modelling of outcomes. The extent to which trial participants represented the total population of sore throat patients referred to ENT clinics was assessed through analysis of site screening logs. Adverse events Information regarding the AEs related to the trial intervention was collected during telephone calls at 1 and 2 weeks post tonsillectomy; all tonsillectomy arm serious adverse events (SAEs) were recorded throughout the duration of the trial for all participants. Economic evaluation The cost-effectiveness of tonsillectomy compared with conservative management was evaluated by estimating the total costs incurred by the NHS and PSS, and averaging these costs across participants in each trial arm. Three different analyses were undertaken: (1) a cost-effectiveness analysis (CEA), (2) a cost–utility analysis (CUA) and (3) a cost–benefit analysis (CBA). All three analyses measured costs using the same methodology but differed in their measure of effectiveness. An incremental cost-effectiveness ratio was estimated for the CEA and the CUA by dividing the difference in average total costs by the difference in average total effects. The CEA estimated the incremental cost per sore throat day avoided. The number of sore throat days was derived from the primary outcome data. The CUA estimated the incremental cost per QALY gained. QALYs were derived using the SF-6D algorithm, which estimates utility values based on responses to the SF-12, which was administered at baseline and 6, 12, 18 and 24 months post randomisation and at the time of a sore throat episode. The CBA estimated the incremental net benefit, comparing costs and benefits in monetary terms. Participants’ WTP values, estimated from the contingent valuation study, were multiplied by participants’ self-reported number of sore throat days to estimate the reduction in patient benefits in monetary terms; from this costs were subtracted to give the net benefit. Qualitative process evaluation Qualitative and cognitive interviews were carried out by researchers from Newcastle University for the feasibility study, pilot and main trial. Interviews were held with adult patients with acute tonsillitis who had been referred to ENT outpatient clinics for recurrent sore throats, ENT staff who were working at a National Trial of Tonsillectomy IN Adults (NATTINA) trial site and GPs. These interviews addressed the acceptability of the trial/treatments, unforeseen consequences from the perspective of participants and how patient experience may shape future research. Statistical analysis The primary statistical analysis was carried out on an intention-to-treat (ITT) basis, retaining patients in their randomised arms and including protocol violator and ineligible patients. Patients randomised to conservative management were asked to commit to ‘deferred surgery’. We anticipated that a number of patients would take the opportunity to switch to surgery. We also undertook sensitivity analyses, including a per-treatment (as treated) and a per-protocol analysis. The cumulative total number of sore throat days reported on a patient level was provided separately for each randomised arm. Negative binomial regression was used to compare these, adjusting for stratification variables (baseline severity as a fixed effect and site as a random effect). The summary comparative statistic reported is the incident rate ratio (IRR). The analysis took account of incomplete weekly returns by use of an exposure variable included in the model. The analysis of secondary outcomes followed a broadly similar strategy to the primary outcome. Analyses were adjusted for baseline severity and site, and repeated measures were analysed using random-effects models with appropriate error structure. Results Primary outcome The participants in this trial reported a median of 27 [interquartile range (IQR) 12–52] sore throats over the full 24 months of follow-up. Fewer sore throats were reported in the tonsillectomy arm (median 23, IQR 11–46) than in the conservative management arm (median 30, IQR 14–65). When the primary outcome (total sore throats) was compared between the two randomised arms on an ITT basis, a reduction in sore throats was seen in the tonsillectomy arm. The tonsillectomy arm had 0.53 [IRR, 95% confidence interval (CI) 0.43 to 0.65] times the total sore throat days over the 24-month period than those in the conservative management arm. Sensitivity analyses on the ITT population confirmed this result. The analysis of the per-protocol population of 224 participants had, on average, a greater reduction in the number of sore throats, with patients in the tonsillectomy arm having 0.42 (IRR 95% CI 0.31 to 0.55) times the total score throats compared with the conservative management arm. Around 25% of participants did not receive the treatment that they were randomised to, which meant that some opted not to receive a tonsillectomy and some opted to cross to tonsillectomy. There is evidence to suggest that those with larger numbers of sore throats following randomisation were more likely to either opt for or remain in the tonsillectomy arm. Conversely, those with slightly smaller numbers of sore throats following randomisation were more likely to remain in conservative management or opt out of the tonsillectomy arm. Despite these crossovers, the ITT, per-protocol and per-treated analyses all confirmed that there was a significant reduction in total sore throats for those randomised to tonsillectomy. Secondary outcome measures The benefits of tonsillectomy were also seen in the secondary outcome measures. Tonsillectomy Outcome Inventory-14 (TOI-14) scores improved in both arms, but show a greater improvement in the tonsillectomy arm than the conservative management arm, where at 12 months the difference between the mean scores was –13.17 units (95% CI –17.41 to –8.92 units), indicating a reduction in symptoms. The SF-12 MCS and SF-12 PCS also show significant and beneficial differences in favour of the tonsillectomy arm over time [SF-12 MCS scores 3.71 units higher (95% CI 2.10 to 5.47) and SF-12 PCS 2.77 units higher (95% CI 0.30 to 5.23) in the tonsillectomy arm than the conservative management arm]. Adverse events There were 52 episodes of post-operative haemorrhage reported in 231 participants undergoing tonsillectomy (22.5%). Of these episodes, 35 were reported as SAEs: 8 as mild events, 22 as moderate events and 5 as severe events. No deaths were reported. Seventeen episodes were recorded as AEs, for which patients did not attend hospital. All episodes of bleeding were managed conservatively with no returns to theatre. Economic evaluation On average, tonsillectomy was more costly and more effective than conservative management. In the CEA, the incremental cost to avoid a sore throat episode was £24 per sore throat day. From the contingent valuation, the mean WTP to avoid a sore throat day was £43 (95% CI £2 to £100). In the CUA, tonsillectomy had an 87% probability of being considered cost-effective at a £5000 threshold for an additional QALY; this increased to 100% as the threshold values for an additional QALY increased. In the CBA, tonsillectomy had a 69% probability of having a higher net benefit than conservative management. Qualitative study Trial processes were deemed as acceptable, with only a few sites experiencing barriers to treatment. The use of technology to collect data was particularly well received. However, there were some challenges with recruitment, particularly for staff who lacked equipoise. ENT staff alluded to having to negotiate surgery dates with patients, which, at times, meant that they had to deviate from trial protocols. Some patients did not fully understand the process of randomisation. Patients who had received surgery were unanimous in reporting to be happy to have undertaken this, despite the challenging recovery period. Limitations There was some evidence that those with the most severe extent of disease were reluctant to enter the study (around 5 points higher scores overall on the TOI-14). Some symptoms may not be a result of tonsillitis. Not all patients were offered, or chose, to watch the trial recruitment video. The ITT analysis is likely to offer a conservative underestimate of the true impact of tonsillectomy in reducing sore throat days, as a result of patients crossing over to receive tonsillectomy. A challenge of the economic evaluation was the progressive loss of data over the 24-month follow-up. Conclusions Tonsillectomy in adults is a clinically effective intervention. It was more costly but had a high probability of being considered cost-effective over the range of analyses conducted. Participants with recurrent tonsillitis, who met current UK NHS guidelines to undergo tonsillectomy, suffered significantly fewer sore throat days over 24 months than similar participants treated conservatively. How should health services react? Pre-NATTINA, UK guidelines were a translation of level 1 evidence in children, applied to adults. Access to tonsillectomy in the UK was governed by application of national guidance, which is predicated on a qualifying number of episodes of tonsillitis. NATTINA participants in the tonsillectomy arm reported, on average, fewer healthcare contacts, fewer sore throat days and higher QALYs than those in the conservative management arm. Within the UK, tonsillectomy is listed as a ‘procedure of limited clinical value’ (The Royal College of Surgeons of England. Procedures of Limited Clinical Value: Royal College of Surgeons Briefing. London: The Royal College of Surgeons of England; 2011). To the best of our knowledge, NATTINA is the first definitive trial to demonstrate that tonsillectomy performed according to the current UK national guidelines is effective for patients, and the probability of it being considered cost-effective is high. Guideline reassessment, in particular how guidelines translate into healthcare commissioning, is called for. How should practitioners and patients respond to these findings? We have identified communication issues at the primary–secondary care interface in our qualitative work. There is, therefore, a need to convert the findings of NATTINA into a practical decision support tool for patients and surgeons. Implications for research (in priority order) The top research priority to emerge from NATTINA is to determine the optimum timing of tonsillectomy in adults with recurrent acute tonsillitis. Work is required also to optimise metrics for disease burden severity, and to exploit the novel real-time data collection methods elaborated in NATTINA. There is also a need to better understand optimum treatment strategies, including oral steroids, for tonsillitis in primary care. Trial registration This trial is registered as ISRCTN55284102. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 12/146/06) and is published in full in Health Technology Assessment; Vol. 27, No. 31. See the NIHR Funding and Awards website for further award information.

Objectives This study aimed to develop a simulation model to support orthopaedic elective capacity planning.Methods An open-source, generalisable discrete-event simulation was developed, including a web-based application. The model used anonymised patient records between 2016 and 2019 of elective orthopaedic procedures from a National Health Service (NHS) Trust in England. In this paper, it is used to investigate scenarios including resourcing (beds and theatres) and productivity (lengths of stay, delayed discharges and theatre activity) to support planning for meeting new NHS targets aimed at reducing elective orthopaedic surgical backlogs in a proposed ring-fenced orthopaedic surgical facility. The simulation is interactive and intended for use by health service planners and clinicians.Results A higher number of beds (65–70) than the proposed number (40 beds) will be required if lengths of stay and delayed discharge rates remain unchanged. Reducing lengths of stay in line with national benchmarks reduces bed utilisation to an estimated 60%, allowing for additional theatre activity such as weekend working. Further, reducing the proportion of patients with a delayed discharge by 75% reduces bed utilisation to below 40%, even with weekend working. A range of other scenarios can also be investigated directly by NHS planners using the interactive web app.Conclusions The simulation model is intended to support capacity planning of orthopaedic elective services by identifying a balance of capacity across theatres and beds and predicting the impact of productivity measures on capacity requirements. It is applicable beyond the study site and can be adapted for other specialties.

Biomass crops provide significant potential to substitute for fossil fuels and mitigate against climate change. It is widely acknowledged that significant scale up of biomass crops is required to help reach net zero targets. Miscanthus is a leading biomass crop embodying many characteristics that make it a highly sustainable source of biomass but planted area remains low. Miscanthus is commonly propagated via rhizome, but efficient alternatives may increase uptake and help diversify the cultivated crop. Using seed-propagate plug plants of Miscanthus has several potential benefits such as improving propagation rates and scale up of plantations. Plugs also provide an opportunity to vary the time and conditions under protected growth, to achieve optimal plantlets before planting. We varied combinations of glasshouse growth period and field planting dates under UK temperate conditions, which demonstrated the special importance of planting date on yield, stem number and establishment rates of Miscanthus. We also propagated Miscanthus in four different commercial plug designs that contained different volumes of substrate, the resulting seedlings were planted at three different dates into field trials. In the glasshouse, plug design had significant effects on above and belowground biomass accumulation and at a later time point belowground growth was restricted in some plug designs. After subsequent growth in the field, plug design and planting date had a significant effect on yield. The effects of plug design on yield were no longer significant after a second growth season but planting date continued to have a significant effect. After the second growth year, it was found that planting date had a significant effect on surviving plants, with the mid-season planting producing higher survival rates over all plug types.Establishment was positively correlated with DM biomass produced in the first growth season. Sowing date had a significant effect on establishment but the impacts of plug design were more nuanced and were significant at later planting dates. We discuss the potential to use the flexibility afforded by seed propagation of plug plants to deliver significant impacts in achieving high yield and establishment of biomass crops during the critical first two years of growth.

Objectives To identify risk factors associated with prolonged length of hospital stay and staying in hospital longer than medically necessary following primary knee replacement surgery.Design Retrospective, longitudinal observational study.Setting Elective knee replacement surgeries between 2016 and 2019 were identified using routinely collected data from an NHS Trust in England.Participants There were 2295 knee replacement patients with complete data included in analysis. The mean age was 68 (SD 11) and 60% were female.Outcome measures We assessed a binary length of stay outcome (>7 days), a continuous length of stay outcome (≤30 days) and a binary measure of whether patients remained in hospital when they were medically fit for discharge.Results The mean length of stay was 5.0 days (SD 3.9), 15.4% of patients were in hospital for >7 days and 7.1% remained in hospital when they were medically fit for discharge. Longer length of stay was associated with older age (b=0.08, 95% CI 0.07 to 0.09), female sex (b=0.36, 95% CI 0.06 to 0.67), high deprivation (b=0.98, 95% CI 0.47 to 1.48) and more comorbidities (b=2.48, 95% CI 0.15 to 4.81). Remaining in hospital beyond being medically fit for discharge was associated with older age (OR=1.07, 95% CI 1.05 to 1.09), female sex (OR=1.71, 95% CI 1.19 to 2.47) and high deprivation (OR=2.27, 95% CI 1.27 to 4.06).Conclusions The regression models could be used to identify which patients are likely to occupy hospital beds for longer. This could be helpful in scheduling operations to aid hospital efficiency by planning these patients’ operations for when the hospital is less busy.

Abstract Data visualizations are a valuable tool used during both statistical analysis and the interpretation of results as they graphically reveal useful information about the structure, properties and relationships between variables, which may otherwise be concealed in tabulated data. In disciplines like medicine and the social sciences, where collected data include sensitive information about study participants, the sharing and publication of individual-level records is controlled by data protection laws and ethico-legal norms. Thus, as data visualizations – such as graphs and plots – may be linked to other released information and used to identify study participants and their personal attributes, their creation is often prohibited by the terms of data use. These restrictions are enforced to reduce the risk of breaching data subject confidentiality, however they limit analysts from displaying useful descriptive plots for their research features and findings. Here we propose the use of anonymization techniques to generate privacy-preserving visualizations that retain the statistical properties of the underlying data while still adhering to strict data disclosure rules. We demonstrate the use of (i) the well-known k-anonymization process which preserves privacy by reducing the granularity of the data using suppression and generalization, (ii) a novel deterministic approach that replaces individual-level observations with the centroids of each k nearest neighbours, and (iii) a probabilistic procedure that perturbs individual attributes with the addition of random stochastic noise. We apply the proposed methods to generate privacy-preserving data visualizations for exploratory data analysis and inferential regression plot diagnostics, and we discuss their strengths and limitations.

Communities of practice (CoPs) can provide opportunities for diverse and inclusive groups to convene, share, collaborate, and support others. Using a self-study research approach combined with a visual research method, this study explores both scholarly and practice-based insights to describe the anticipated attributes of a high functioning CoP for the support of collaborative engagement in Scholarship of Teaching and Learning (SoTL). The following nine emergent attributes are identified: 1) Structures; (2) Social environments; (3) Diversity; (4) Knowledge, learning and ideas; (5) Support; (6) Shared leadership; (7) Risk; (8) Results and impact; and (9) Growth over time. This study contributes to the growing body of knowledge related to the value of visual research methods in collaborative self-study. Moreover, the results of this self-study deepen understanding about the practice and role of convenors and organizers of a grass-roots, campus-wide SoTL CoP initiative.

Introduction Pulmonary rehabilitation (PR), an exercise and education programme for people with chronic lung disease, aims to improve exercise capacity, breathlessness and quality of life. Most evidence to support PR is from trials that use specialist exercise equipment, for example, treadmills (PR-gym). However, a significant proportion of programmes do not have access to specialist equipment with training completed with minimal exercise equipment (PR-min). There is a paucity of robust literature examining the efficacy of supervised, centre-based PR-min. We aim to determine whether an 8-week supervised, centre-based PR-min programme is non-inferior to a standard 8-week supervised, centre-based PR-gym programme in terms of exercise capacity and health outcomes for patients with chronic lung disease.Methods and analysis Parallel, two-group, assessor-blinded and statistician-blinded, non-inferiority randomised trial. 436 participants will be randomised using minimisation at the individual level with a 1:1 allocation to PR-min (intervention) or PR-gym (control). Assessment will take place pre-PR (visit 1), post-PR (visit 2) and 12 months following visit 1 (visit 3). Exercise capacity (incremental shuttle walk test), dyspnoea (Chronic Respiratory Questionnaire (CRQ)-Dyspnoea), health-related quality of life (CRQ), frailty (Short Physical Performance Battery), muscle strength (isometric quadriceps maximum voluntary contraction), patient satisfaction (Global Rating of Change Questionnaire), health economic as well as safety and trial process data will be measured. The primary outcome is change in exercise capacity between visit 1 and visit 2. Two sample t-tests on an intention to treat basis will be used to estimate the difference in mean primary and secondary outcomes between patients randomised to PR-gym and PR-min.Ethics and dissemination London-Camden and Kings Cross Research Ethics Committee and Health Research Authority have approved the study (18/LO/0315). Results will be submitted for publication in peer-reviewed journals, presented at international conferences, disseminated through social media, patient and public routes and directly shared with stakeholders.Trial registration number ISRCTN16196765.

Stromal interaction molecule 1 (STIM1), the sarcoplasmic reticulum (SR) transmembrane protein, activates store-operated Ca2+ entry (SOCE) in skeletal muscle and, thereby, coordinates Ca2+ homeostasis, Ca2+-dependent gene expression, and contractility. STIM1 occupies space in the junctional SR membrane of the triads and the longitudinal SR at the Z-line. How STIM1 is organized and is retained in these specific subdomains of the SR is unclear. Here, we identified desmin, the major type III intermediate filament protein in muscle, as a binding partner for STIM1 based on a yeast 2-hybrid screen. Validation of the desmin-STIM1 interaction by immunoprecipitation and immunolocalization confirmed that the CC1-SOAR domains of STIM1 interact with desmin to enhance STIM1 oligomerization yet limit SOCE. Based on our studies of desmin-KO mice, we developed a model wherein desmin connected STIM1 at the Z-line in order to regulate the efficiency of Ca2+ refilling of the SR. Taken together, these studies showed that desmin-STIM1 assembles a cytoskeletal-SR connection that is important for Ca2+ signaling in skeletal muscle.

Abstract Background Older adults are advised to attend a number of preventive health checks to preserve health and identify risk factors for disease. Previous research has identified a number of health and social factors, labelled as predisposing, enabling and need factors, using Andersen’s Behavioural Model of Health Service Use, that are associated with health care utilisation. We aimed to assess associations between factors from childhood and adulthood, and health check attendance in later life in a British birth cohort study. Methods For 2370 study members from the MRC National Survey of Health and Development (NSHD), health check attendance was assessed at age 68. Study members were asked if they: attended blood pressure and cholesterol checks, had their eyes tested, received the influenza vaccine, attended colon cancer screening and dental checks. Health and social factors from childhood and adulthood were used in binomial regression models to test associations with health check attendance in men and women. Results Health check attendance was high; 41% reported attending all six health checks within the recommended time frame. In multivariable models, being a non-smoker and having more health conditions in adulthood were associated with greater health check attendance in men and women. In women, childhood socioeconomic advantage, being more physically active in midlife and previously attending screening procedures, and in men, greater self-organisation in adolescence and being married were associated with attending more health checks in later life, following adjustments for childhood and adulthood factors. Conclusions A number of predisposing, enabling and need factors from childhood and adulthood were found to be associated with health check attendance at age 68, demonstrating the relevance of applying a life course perspective to Andersen’s model in investigating health check attendance in later life. Health related factors were found to be stronger correlates of health check attendance than socioeconomic factors.

Objective Internationally recognised specialist breast cancer scientists, clinicians and healthcare professionals have published breast cancer research gaps that are informing research funding priorities in the UK and worldwide. We aimed to determine the breast cancer research priorities of the public to compare with those identified by clinicians and scientists.Design We conducted a qualitative study and thematic analysis using ‘listening events’ where patients with breast cancer and public representatives used a patient’s breast cancer journey to identify research themes.Participants and setting Female participants were recruited from attendees at participating hospitals and support groups in the northwest of England, including patients, their family and friends as well as staff at a local retail centre.Intervention A framework approach was used to analyse transcribed discussions until thematic saturation was reached.Main outcome measures Breast cancer research priorities were identified from participant discussions and compared with the published gaps identified by scientists and healthcare professionals.Results Thematic saturation was reached after 27 female participants participated in listening events. Our participants consistently focused on improved methods of dissemination of information and improving education on the signs and symptoms of breast cancer. This was not highlighted by scientists or healthcare professionals. There was strong emphasis on quality of life-related issues such as side effects of treatment. There was some agreement between the priorities deduced by our study and those of the professionals in the areas of screening, prevention and breast reconstruction.Conclusion Our study identified some research themes that were not identified by scientists and healthcare professionals in two earlier landmark studies. This highlights the importance of including patients and public representatives when setting research priorities. The results should be used to guide investigators when planning future studies and for funding bodies in allocating resources for future projects.

Background: Palliative care is recommended to help meet the needs of patients with progressive non-cancer conditions, such as long-term neurological conditions. However, few trials have tested palliative care in this population. Objectives: To determine the effectiveness and cost-effectiveness of short-term integrated palliative care in improving symptoms, improving patient- and caregiver-reported outcomes and reducing hospital use for people severely affected by long-term neurological conditions. Design: Pragmatic, randomised controlled, multicentre, fast-track trial, with an embedded qualitative component and surveys. Setting: Seven UK centres (South London, Nottingham, Liverpool, Cardiff, Brighton, Ashford and Sheffield) with multiprofessional palliative care teams and neurology services. Participants: People living with multiple sclerosis, idiopathic Parkinson’s disease, motor neurone disease, multiple system atrophy or progressive supranuclear palsy, with unresolved symptoms and/or complex psychosocial needs. The qualitative study involved patients, caregivers and health-care staff. Interventions: Participants were randomised to receive short-term integrated palliative care, delivered by multiprofessional teams, immediately or after a 12-week wait (standard care group). Main outcome measures: The primary outcome was a combined score of eight symptoms measured by the Integrated Palliative care Outcome Scale for Neurological conditions 8 symptom subscale (IPOS Neuro-S8) at 12 weeks. Secondary outcomes included patients’ other physical and psychological symptoms, quality of life (EuroQol-5 Dimensions, five-level version), care satisfaction, caregiver burden, service use and cost, and harms. Data were analysed using multiple imputation, generalised linear mixed models, incremental cost-effectiveness ratios (threshold was the National Institute for Health and Care Excellence £20,000 per quality-adjusted life-year) and cost-effectiveness planes. Qualitative data were analysed thematically. Results: We recruited 350 patients and 229 caregivers. There were no significant between-group differences for primary or secondary outcomes. Patients receiving short-term integrated palliative care had a significant improvement, from baseline to 12 weeks, on the primary outcome IPOS Neuro-S8 (–0.78, 95% confidence interval –1.29 to –0.26) and the secondary outcome of 24 physical symptoms (–1.95, 99.55% confidence interval –3.60 to –0.30). This was not seen in the control group, in which conversely, care satisfaction significantly reduced from baseline to 12 weeks (–2.89, 99.55% confidence interval –5.19 to –0.59). Incremental cost-effectiveness ratios were smaller than the set threshold (EuroQol-5 Dimensions index score –£23,545; IPOS Neuro-S8 –£1519), indicating that the intervention provided cost savings plus better outcomes. Deaths, survival and hospitalisations were similar between the two groups. Qualitative data suggested that the impact of the intervention encompassed three themes: (1) adapting to losses and building resilience, (2) attending to function, deficits and maintaining stability, and (3) enabling caregivers to care. Conclusions: Our results indicate that short-term integrated palliative care provides improvements in patient-reported physical symptoms at a lower cost and without harmful effects when compared with standard care. Limitations: Outcome measures may not have been sensitive enough to capture the multidimensional changes from the intervention. Our surveys found that the control/standard and intervention services were heterogeneous. Future work: Refining short-term integrated palliative care and similar approaches for long-term neurological conditions, focusing on better integration of existing services, criteria for referral and research to improve symptom management. Trial registration: Current Controlled Trials ISRCTN18337380. Funding: This project was funded by the National Institute for Health Research (NIHR) Health Services and Delivery Research programme and will be published in full in Health Services and Delivery Research; Vol. 8, No. 36. See the NIHR Journals Library website for further project information.

Background: Patients admitted to hospital with a terminal illness and uncertain recovery often receive inconsistent care and do not have the opportunity to die in their preferred place of death. Previous end-of-life care packages, such as the Liverpool Care Pathway for the Dying Patient, have sometimes been badly implemented. The AMBER (Assessment; Management; Best practice; Engagement; Recovery uncertain) care bundle was developed to remedy this. It has not been evaluated in a randomised trial, but a definitive trial would face many hurdles. Objective: To optimise the design of and determine the feasibility of a pragmatic, multicentre, cluster randomised controlled trial of the AMBER care bundle compared with best standard care. Design: A feasibility cluster randomised controlled trial including semistructured interviews with patients and relatives, focus groups with health-care professionals, non-participant observations of multidisciplinary team meetings, a standard care survey, heat maps and case note reviews. Retrospective data were collected from the family or close friends of deceased patients via a bereavement survey. Setting: Four general medical wards at district general hospitals in England. Participants: There were 65 participants (control, n = 36; intervention, n = 29). There were 24 interviews, four focus groups, 15 non-participant meeting observations, six case note reviews and three heat maps, and 15 of out 23 bereavement, standard care surveys were completed. Intervention: The AMBER care bundle is implemented by a nurse facilitator. It includes the development and documentation of a medical plan, consideration of outcomes, resuscitation and escalation status and daily plan revisiting. The AMBER care bundle encourages staff, patients and families to talk openly about their preferences and priorities should the worst happen. Main outcome measures: Two ‘candidate’ primary outcomes were selected to be evaluated for a future definitive trial: Integrated Palliative care Outcome Scale patient/family anxiety and communication subscale and ‘howRwe’. The secondary outcome measures were Integrated Palliative care Outcome Scale symptoms, Australian-modified Karnofsky Performance Status scale, EuroQol-5 Dimensions, five-level version, Client Service Receipt Inventory, recruitment rate, intervention fidelity and intervention acceptability. Results: Data were collected for 65 patients. This trial was not powered to measure clinical effectiveness, but variance and changes observed in the Integrated Palliative care Outcome Scale subscale indicated that this measure would probably detect differences within a definitive trial. It was feasible to collect data on health, social and informal care service use and on quality of life at two time points. The AMBER care bundle was broadly acceptable to all stakeholders and was delivered as planned. The emphasis on ‘clinical uncertainty’ prompted health-care professional awareness of often-overlooked patients. Reviewing patients’ AMBER care bundle status was integrated into routine practice. Refinements included simplifying the inclusion criteria and improving health-care professional communication training. Improvements to trial procedures included extending the time devoted to recruitment and simplifying consent procedures. There was also a recommendation to reduce data collected from patients and relatives to minimise burden. Limitations: The recruitment rate was lower than anticipated. The inclusion criteria for the trial were difficult to interpret. Information sheets and consent procedures were too detailed and lengthy for the target population. Health-care professionals’ enthusiasm and specialty were not considered while picking trial wards. Participant recruitment took place later during hospital admission and the majority of participants were lost to follow-up because they had been discharged. Those who participated may have different characteristics from those who did not. Conclusions: This feasibility trial has demonstrated that an evaluation of the AMBER care bundle among an acutely unwell patient population, although technically possible, is not practical or feasible. The intervention requires optimisation. Trial registration: Current Controlled Trials ISRCTN36040085. National Institute for Health Research (NIHR) Portfolio registration number 32682. Funding: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 23, No. 55. See the NIHR Journals Library website for further project information.

[This corrects the article DOI: 10.1371/journal.pmed.1002782.].

BackgroundLow socioeconomic position (SEP) is recognized as a risk factor for worse health outcomes. How socioeconomic factors influence end-of-life care, and the magnitude of their effect, is not understood. This review aimed to synthesise and quantify the associations between measures of SEP and use of healthcare in the last year of life.Methods and findingsMEDLINE, EMBASE, PsycINFO, CINAHL, and ASSIA databases were searched without language restrictions from inception to 1 February 2019. We included empirical observational studies from high-income countries reporting an association between SEP (e.g., income, education, occupation, private medical insurance status, housing tenure, housing quality, or area-based deprivation) and place of death, plus use of acute care, specialist and nonspecialist end-of-life care, advance care planning, and quality of care in the last year of life. Methodological quality was evaluated using the Newcastle-Ottawa Quality Assessment Scale (NOS). The overall strength and direction of associations was summarised, and where sufficient comparable data were available, adjusted odds ratios (ORs) were pooled and dose-response meta-regression performed. A total of 209 studies were included (mean NOS quality score of 4.8); 112 high- to medium-quality observational studies were used in the meta-synthesis and meta-analysis (53.5% from North America, 31.0% from Europe, 8.5% from Australia, and 7.0% from Asia). Compared to people living in the least deprived neighbourhoods, people living in the most deprived neighbourhoods were more likely to die in hospital versus home (OR 1.30, 95% CI 1.23-1.38, p < 0.001), to receive acute hospital-based care in the last 3 months of life (OR 1.16, 95% CI 1.08-1.25, p < 0.001), and to not receive specialist palliative care (OR 1.13, 95% CI 1.07-1.19, p < 0.001). For every quintile increase in area deprivation, hospital versus home death was more likely (OR 1.07, 95% CI 1.05-1.08, p < 0.001), and not receiving specialist palliative care was more likely (OR 1.03, 95% CI 1.02-1.05, p < 0.001). Compared to the most educated (qualifications or years of education completed), the least educated people were more likely to not receive specialist palliative care (OR 1.26, 95% CI 1.07-1.49, p = 0.005). The observational nature of the studies included and the focus on high-income countries limit the conclusions of this review.ConclusionsIn high-income countries, low SEP is a risk factor for hospital death as well as other indicators of potentially poor-quality end-of-life care, with evidence of a dose response indicating that inequality persists across the social stratum. These findings should stimulate widespread efforts to reduce socioeconomic inequality towards the end of life.

BackgroundPatients with serious mental disorders have poorer healthcare outcomes at the end of life and are at greater risk of dying from unnatural causes.AimsTo explore place of death and demographic and clinical correlates of unnatural causes of death in patients with serious mental disorders.MethodRoutinely collected patient data were used to explore bivariate and adjusted associations between covariates and natural/unnatural cause of death.ResultsIn multivariable analysis (n = 1029), dying at home (odds ratio (OR) = 1.87, 95% CI 1.03–3.40), ‘other’ locations (OR = 16.50, 95% CI 7.57–36.00), younger age (OR = 17.26, 95% CI 8.28–36.00) and a diagnosis other than schizophrenia spectrum disorder (OR = 1.69, 95% CI 1.04–2.73) were correlates of unnatural cause of death.ConclusionsDeaths from unnatural causes were high and more likely to occur at home and non-healthcare settings. Unnatural causes of death were higher in younger patients with non-schizophrenia spectrum disorder diagnoses.Declaration of interestF.G. has received support or honoraria for CME, advisory work and lectures from Bristol-Myers Squibb, Janssen, Lundbeck, Otsuka, Roche, and Sunovion, and has a family member with professional links to Lilly and GSK, including shares.

In academic contexts, digital games are often studied as texts or are used as pedagogical tools to teach basic concepts in early education situations. Less usefully, their systems and economies are often co-opted and decontextualized in short-sighted attempts to “gamify” various aspects of learning or training. However, given that games are highly controlled, conditional, choice-and-consequence-based, problem-solving environments in which players are expected to interact with simulated settings and elements after agreeing to take on particular roles and subject positions, there are promising potential uses of these experiences in academic contexts that have not been fully considered. Motivated by the imperative to explore alternative modes and methods of scholarly research and communication, and guided by the values of open social scholarship practices, this paper reconsiders games not as things to study, but as instruments to study with. Given that games can function as simulations, models, arguments and creative collaboratories, game-based inquiry can be used as a potential method of post-secondary and post-graduate humanities research and scholarly communication. While these ideas have been explored in a preliminary way in relation to a number of different academic disciplines (Donchin 1995; Boot 2015; Mitgutsch and Weise 2011; Westecott 2011) this paper is meant to catalyse a humanities-calibrated consideration of the pragmatics and potentials of game-based research, games as instances of critical making and scholarly communication, and more complex forms of game-based learning than those currently practiced. A number of examples that make use of the open source Twine platform will be featured.

Birth cohort studies generate huge amounts of data, and as a consequence are a source of many peer reviewed publications. We have taken the list of publications from the Avon Longitudinal Study of Parents and Children UK birth cohort, filtered, de-duplicated and cleaned it to generate a bibliographic research data set. This dataset could be used for accurate reporting and monitoring of the impact of the study as well as bibliometric research.

Antibiotic-tolerant bacterial biofilms are notorious in causing PJI. Antibiotic loaded calcium sulfate bead (CSB) bone void fillers and PMMA cement and powdered vancomycin (VP) have been used to achieve high local antibiotic concentrations; however, the effect of drainage on concentration is poorly understood. We designed an in vitro flow reactor which provides post-surgical drainage rates after knee revision surgery to determine antibiotic concentration profiles. Tobramycin and vancomycin concentrations were determined using LCMS, zones of inhibition confirmed potency and the area under the concentration–time curve (AUC) at various time points was used to compare applications. Concentrations of antibiotcs from the PMMA and CSB initially increased then decreased before increasing after 2 to 3 h, correlating with decreased drainage, demonstrating that concentration was controlled by both release and flow rates. VP achieved the greatest AUC after 2 h, but rapidly dropped below inhibitory levels. CSB combined with PMMA achieved the greatest AUC after 2 h. The combination of PMMA and CSB may present an effective combination for killing biofilm bacteria; however, cytotoxicity and appropriate antibiotic stewardship should be considered. The model may be useful in comparing antibiotic concentration profiles when varying fluid exchange is important. However, further studies are required to assess its utility for predicting clinical efficacy.

In addition to their role in apoptosis, caspases are also involved in mediating non-apoptotic events. Here the authors show that the Drosophilamyosin family member CRINKLED and its mammalian counterpart act as substrate adaptor that facilitate caspase-mediated cleavage and localised kinase activity.

ABSTRACT Objectives DataSHIELD (www.datashield.ac.uk) was born of the requirement in the biomedical and social sciences to co-analyse individual patient data (microdata) from different sources, without disclosing identity or sensitive information. Under DataSHIELD, raw data never leaves the data provider and no microdata or disclosive information can be seen by the researcher. The analysis is taken to the data - not the data to the analysis. Text data can be very disclosive in the biomedical domain (patient records, GP letters etc). Similar, but different, issues are present in other domains - text could be copyrighted, or have a large IP value, making sharing impractical. Approach By treating text in an analogous way to individual patient data we assessed if DataSHIELD could be adapted and implemented for text analysis, and circumvent the key obstacles that currently prevent it. Results Using open digitised text data held by the British Library, a DataSHIELD proof-of-concept infrastructure and prototype DataSHIELD functions for free text analysis were developed. Conclusions Whilst it is possible to analyse free text within a DataSHIELD infrastructure, the challenge is creating generalised and resilient anti-disclosure methods for free text analysis. There are a range of biomedical and health sciences applications for DataSHIELD methods of privacy protected analysis of free text including analysis of electronic health records and analysis of qualitative data e.g. from social media.

ABSTRACT Objectives In several disciplines such as in biomedicine and social sciences the analysis of individual-level data or the co-analysis of data from different studies requires the pooling and the sharing of those data. However, sharing and combining sensitive individual-level data is often prohibited by ethico-legal constraints and other barriers such as the control maintenance and the huge sample sizes. The graphical illustration of microdata is also often forbidden as can potentially be unsecured on the identification of sensitive information. For example the plot of a standard scatterplot is disclosive as can explicitly specify the exact values of two measurements for each single individual. Approach DataSHIELD (www.datashield.ac.uk) is a novel approach that allows the analysis of sensitive individual-level data and the co-analysis of such data from several studies simultaneously without physically pooling the data. Results DataSHIELD functionality consists of several functions that provide the flexibility of performing data analysis through different statistical techniques. A part of this environment includes a number of graphical-related functions for the graphical illustration of the statistical properties and relationships between different variables. We overview the graphical functions in DataSHIELD (ds.histogram, ds.heatmapPlot, ds.contourPlot) and demonstrate a number of new functions including ds.scatterPlot and ds.boxPlot developed based on the application of different computational approaches like the k-Nearest Neighbours algorithm and ensuring privacy protected analysis. Conclusion DataSHIELD graphical functionality has certain methodological features for the representation of the relationships between different variables preserving their statistical properties and assuring the data privacy protection. These graphical approaches can be used or enhanced for application in various areas where confidentiality and information sensitivity is considered, for example in longitudinal data and survival analysis, in epidemiological studies, in geospatial analysis and several others.

ABSTRACT Objectives The effective exploitation of what are often called big data is increasingly important. They provide the evidence in evidence-based health care and underpin scientific progress in many domains including social/economic policy. Typically, an optimal analysis involves working directly with microdata; i.e. the detailed data relating to each individual in the dataset. But there are many ethico-legal and other governance restrictions on physically sharing microdata. Furthermore, researchers or institutions may have an extensive intellectual property investment in complex microdata and although keen for other researchers to analyse their data they may not wish to give them a physical copy. These restrictions can discourage the use of optimum approaches to analysing pivotal data and slow scientific progress. Data science groups across the world are exploring privacy-protected approaches to analysing microdata without having to physically share the data. Approach A two day international workshop was arranged focussing on privacy protected approaches to data analysis – particularly federated analysis where raw data remain at their original site of collection. The workshop considered the range of approaches that exist, and those that are currently being developed. It explored the strengths, weaknesses, opportunities and challenges associated with these methods and identified situations where specific approaches have a particularly important role. The workshop included a number of practical sessions where potential users could watch demonstrations of the various approaches in action and run analyses themselves. Results The Data Analysis with Privacy Protection for Epidemiological Research (DAPPER) workshop was held 22-23rd August 2016, Bristol. We report back to the broader community on the outcomes of this workshop that focussed on exploring current approaches, tools and technical solutions that facilitate sensitive data to be shared and analysed. Conclusions The workshop has helped map out key opportunities and challenges and assisted potential users, developers and other stakeholders (e.g. funders/journals) to recognise the strengths and weaknesses of different privacy protected analytic approaches. The workshop will encourage further methodological work in this field and better informed application of existing methods.