Field Performance and Quality of Hybrid Winter Wheat.

End of Project ReportAn assessment of hybrid winter wheat was carried out over three seasons to determine the commercial potential of hybrid varieties under Irish conditions. The studies examined the effects of reduced seeding rate on hybrid grain yield and quality in comparison to pure-line varieties. A comparison of the hybrid varieties available was also carried out and the higher yielding hybrids were then compared with the best pure-line varieties in terms of grain yield and quality, and response to fungicide. The results indicated that in good sowing conditions hybrids can give greater yields than pure-line varieties at reduced seeding rates, but the effect is not large or consistent. There was generally no effect of seeding rate on the grain quality of hybrid varieties but crop lodging occurred in one season at high seeding rates. Of the hybrid varieties examined, Mercury and Hyno Esta were the two better varieties in terms of grain yield; there was little difference between the hybrids examined in terms of grain quality. The best hybrid varieties did not give consistently higher yields or quality than the best pure-line varieties and exhibited a similar response to fungicide application as the pure-line varieties. It is concluded that when the price differential between seed of pure-line varieties and hybrid varieties is taken into account, the winter wheat hybrid varieties currently available do not offer any economic advantages to commercial growers at the present time

Short-chain fatty acid level and field cancerization show opposing associations with enteroendocrine cell number and neuropilin expression in patients with colorectal adenoma

BACKGROUND: Previous reports have suggested that the VEGF receptor neuropilin-1 (NRP-1) is expressed in a singly dispersed subpopulation of cells in the normal colonic epithelium, but that expression becomes dysregulated during colorectal carcinogenesis, with higher levels in tumour suggestive of a poor prognosis. We noted that the spatial distribution and morphology if NRP-1 expressing cells resembles that of enteroendocrine cells (EEC) which are altered in response to disease state including cancer and irritable bowel syndrome (IBS). We have shown that NRP-1 is down-regulated by butyrate in colon cancer cell lines in vitro and we hypothesized that butyrate produced in the lumen would have an analogous effect on the colon mucosa in vivo. Therefore we sought to investigate whether NRP-1 is expressed in EEC and how NRP-1 and EEC respond to butyrate and other short-chain fatty acids (SCFA - principally acetate and propionate). Additionally we sought to assess whether there is a field effect around adenomas. METHODOLOGY: Biopsies were collected at the mid-sigmoid, at the adenoma and at the contralateral wall (field) of 28 subjects during endoscopy. Samples were fixed for IHC and stained for either NRP-1 or for chromogranin A (CgA), a marker of EEC. Stool sampling was undertaken to assess individuals' butyrate, acetate and propionate levels. RESULT: NRP-1 expression was inversely related to SCFA concentration at the colon landmark (mid-sigmoid), but expression was lower and not related to SCFA concentration at the field. Likewise CgA+ cell number was also inversely related to SCFA at the landmark, but was lower and unresponsive at the field. Crypt cellularity was unaltered by field effect. A colocalisation analysis showed only a small subset of NRP-1 localised with CgA. Adenomas showed extensive, weaker staining for NRP-1 which contrastingly correlated positively with butyrate level. Field effects cause this relationship to be lost. Adenoma tissue shows dissociation of the co-regulation of NRP-1 and EEC. CONCLUSION: NRP-1 is inversely associated with levels of butyrate and other SCFA in vivo and is expressed in a subset of CgA expressing cells. EEC number is related to butyrate level in the same way

Haemorrhoidal artery ligation versus rubber band ligation for the management of symptomatic second-degree and third-degree haemorrhoids (HubBLe): a multicentre, open-label, randomised controlled trial.

BACKGROUND: Optimum surgical intervention for low-grade haemorrhoids is unknown. Haemorrhoidal artery ligation (HAL) has been proposed as an efficacious, safe therapy while rubber band ligation (RBL) is a commonly used outpatient treatment. We compared recurrence after HAL versus RBL in patients with grade II-III haemorrhoids. METHODS: This multicentre, open-label, parallel group, randomised controlled trial included patients from 17 acute UK NHS trusts. We screened patients aged 18 years or older presenting with grade II-III haemorrhoids. We excluded patients who had previously received any haemorrhoid surgery, more than one injection treatment for haemorrhoids, or more than one RBL procedure within 3 years before recruitment. Eligible patients were randomly assigned (in a 1:1 ratio) to either RBL or HAL with Doppler. Randomisation was computer-generated and stratified by centre with blocks of random sizes. Allocation concealment was achieved using a web-based system. The study was open-label with no masking of participants, clinicians, or research staff. The primary outcome was recurrence at 1 year, derived from the patient's self-reported assessment in combination with resource use from their general practitioner and hospital records. Recurrence was analysed in patients who had undergone one of the interventions and been followed up for at least 1 year. This study is registered with the ISRCTN registry, ISRCTN41394716. FINDINGS: From Sept 9, 2012, to May 6, 2014, of 969 patients screened, 185 were randomly assigned to the HAL group and 187 to the RBL group. Of these participants, 337 had primary outcome data (176 in the RBL group and 161 in the HAL group). At 1 year post-procedure, 87 (49%) of 176 patients in the RBL group and 48 (30%) of 161 patients in the HAL group had haemorrhoid recurrence (adjusted odds ratio [aOR] 2·23, 95% CI 1·42-3·51; p=0·0005). The main reason for this difference was the number of extra procedures required to achieve improvement (57 [32%] participants in the RBL group and 23 [14%] participants in the HAL group had a subsequent procedure for haemorrhoids). The mean pain 1 day after procedure was 3·4 (SD 2·8) in the RBL group and 4·6 (2·8) in the HAL group (difference -1·2, 95% CI -1·8 to -0·5; p=0·0002); at day 7 the scores were 1·6 (2·3) in the RBL group and 3·1 (2·4) in the HAL group (difference -1·5, -2·0 to -1·0; p<0·0001). Pain scores did not differ between groups at 21 days and 6 weeks. 15 individuals reported serious adverse events requiring hospital admission. One patient in the RBL group had a pre-existing rectal tumour. Of the remaining 14 serious adverse events, 12 (7%) were among participants treated with HAL and two (1%) were in those treated with RBL. Six patients had pain (one treated with RBL, five treated with HAL), three had bleeding not requiring transfusion (one treated with RBL, two treated with HAL), two in the HAL group had urinary retention, two in the HAL group had vasovagal upset, and one in the HAL group had possible sepsis (treated with antibiotics). INTERPRETATION: Although recurrence after HAL was lower than a single RBL, HAL was more painful than RBL. The difference in recurrence was due to the need for repeat bandings in the RBL group. Patients (and health commissioners) might prefer such a course of RBL to the more invasive HAL. FUNDING: NIHR Health Technology Assessment programme

Dynamic Blood-Brain Barrier Regulation in Mild Traumatic Brain Injury

Whereas the diagnosis of moderate and severe traumatic brain injury (TBI) is readily visible on current medical imaging paradigms (magnetic resonance imaging [MRI] and computed tomography [CT] scanning), a far greater challenge is associated with the diagnosis and subsequent management of mild TBI (mTBI), especially concussion which, by definition, is characterized by a normal CT. To investigate whether the integrity of the blood-brain barrier (BBB) is altered in a high-risk population for concussions, we studied professional mixed martial arts (MMA) fighters and adolescent rugby players. Additionally, we performed the linear regression between the BBB disruption defined by increased gadolinium contrast extravasation on dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) on MRI and multiple biomechanical parameters indicating the severity of impacts recorded using instrumented mouthguards in professional MMA fighters. MMA fighters were examined pre-fight for a baseline and again within 120 h post-competitive fight, whereas rugby players were examined pre-season and again post-season or post-match in a subset of cases. DCE-MRI, serological analysis of BBB biomarkers, and an analysis of instrumented mouthguard data, was performed. Here, we provide pilot data that demonstrate disruption of the BBB in both professional MMA fighters and rugby players, dependent on the level of exposure. Our data suggest that biomechanical forces in professional MMA and adolescent rugby can lead to BBB disruption. These changes on imaging may serve as a biomarker of exposure of the brain to repetitive subconcussive forces and mTBI

What Lies behind the Wish to Hasten Death? A Systematic Review and Meta-Ethnography from the Perspective of Patients

BACKGROUND: There is a need for an in-depth approach to the meaning of the wish to hasten death (WTHD). This study aims to understand the experience of patients with serious or incurable illness who express such a wish. METHODS AND FINDINGS: Systematic review and meta-ethnography of qualitative studies from the patient's perspective. Studies were identified through six databases (ISI, PubMed, PsycINFO, CINAHL, CUIDEN and the Cochrane Register of Controlled Trials), together with citation searches and consultation with experts. Finally, seven studies reporting the experiences of 155 patients were included. The seven-stage Noblit and Hare approach was applied, using reciprocal translation and line-of-argument synthesis. Six main themes emerged giving meaning to the WTHD: WTHD in response to physical/psychological/spiritual suffering, loss of self, fear of dying, the desire to live but not in this way, WTHD as a way of ending suffering, and WTHD as a kind of control over one's life ('having an ace up one's sleeve just in case'). An explanatory model was developed which showed the WTHD to be a reactive phenomenon: a response to multidimensional suffering, rather than only one aspect of the despair that may accompany this suffering. According to this model the factors that lead to the emergence of WTHD are total suffering, loss of self and fear, which together produce an overwhelming emotional distress that generates the WTHD as a way out, i.e. to cease living in this way and to put an end to suffering while maintaining some control over the situation. CONCLUSIONS: The expression of the WTHD in these patients is a response to overwhelming emotional distress and has different meanings, which do not necessarily imply a genuine wish to hasten one's death. These meanings, which have a causal relationship to the phenomenon, should be taken into account when drawing up care plans

Identification of Surgeon Burnout via a Single-Item Measure

BackgroundBurnout is endemic in surgeons in the UK and linked with poor patient safety and quality of care, mental health problems, and workforce sustainability. Mechanisms are required to facilitate the efficient identification of burnout in this population. Multi-item measures of burnout may be unsuitable for this purpose owing to assessment burden, expertise required for analysis, and cost.AimsTo determine whether surgeons in the UK reporting burnout on the 22-item Maslach Burnout Inventory (MBI) can be reliably identified by a single-item measure of burnout.MethodsConsultant (n = 333) and trainee (n = 217) surgeons completed the MBI and a single-item measure of burnout. We applied tests of discriminatory power to assess whether a report of high burnout on the single-item measure correctly classified MBI cases and non-cases.ResultsThe single-item measure demonstrated high discriminatory power on the emotional exhaustion burnout domain: the area under the curve was excellent for consultants and trainees (0.86 and 0.80), indicating high sensitivity and specificity. On the depersonalisation domain, discrimination was acceptable for consultants (0.76) and poor for trainees (0.69). In contrast, discrimination was acceptable for trainees (0.71) and poor for consultants (0.62) on the personal accomplishment domain.ConclusionsA single-item measure of burnout is suitable for the efficient assessment of emotional exhaustion in consultant and trainee surgeons in the UK. Administered regularly, such a measure would facilitate the early identification of at-risk surgeons and swift intervention, as well as the monitoring of group-level temporal trends to inform resource allocation to coincide with peak periods

Design, planning and implementation lessons learnt from a surgical multi-centre randomised controlled trial

Background Increasingly, pragmatic randomised controlled trials are being used to evaluate surgical interventions, although they present particular difficulties in regards to recruitment and retention. Methods Procedures and processes related to implementation of a multi-centre pragmatic surgical randomised controlled trial are discussed. In this surgical trial, forecasting of consent rates based on similar trials and micro-costing of study activities with research partners were undertaken and a video was produced targeting recruiting staff with the aim of aiding recruitment. The baseline assessments were reviewed to ensure the timing did not impact on the outcome. Attrition due to procedure waiting time was monitored and data were triangulated for the primary outcome to ensure adequate follow-up data. Results Forecasting and costing ensured that the recruitment window was of adequate length and adequate resource was available for study procedures at multiple clinics in each hospital. Recruiting staff found the recruitment video useful. The comparison of patient-reported data collected prior to randomisation and prior to treatment provided confidence in the baseline data. Knowledge of participant dropout due to delays in treatment meant we were able to increase the recruitment target in a timely fashion, and along with the triangulation of data sources, this ensured adequate follow-up of randomised participants. Conclusions This paper provides a range of evidence-based and experience-based approaches which, collectively, resulted in meeting our study objectives and from which lessons may be transferable

Field Performance and Quality of Hybrid Winter Wheat.

End of Project ReportAn assessment of hybrid winter wheat was carried out over three seasons to determine the commercial potential of hybrid varieties under Irish conditions. The studies examined the effects of reduced seeding rate on hybrid grain yield and quality in comparison to pure-line varieties. A comparison of the hybrid varieties available was also carried out and the higher yielding hybrids were then compared with the best pure-line varieties in terms of grain yield and quality, and response to fungicide. The results indicated that in good sowing conditions hybrids can give greater yields than pure-line varieties at reduced seeding rates, but the effect is not large or consistent. There was generally no effect of seeding rate on the grain quality of hybrid varieties but crop lodging occurred in one season at high seeding rates. Of the hybrid varieties examined, Mercury and Hyno Esta were the two better varieties in terms of grain yield; there was little difference between the hybrids examined in terms of grain quality. The best hybrid varieties did not give consistently higher yields or quality than the best pure-line varieties and exhibited a similar response to fungicide application as the pure-line varieties. It is concluded that when the price differential between seed of pure-line varieties and hybrid varieties is taken into account, the winter wheat hybrid varieties currently available do not offer any economic advantages to commercial growers at the present time

The PATH to PPE Mastery - Programme for Assessment and Training in HCID (High Consequence Infectious Diseases) PPE (Personal Protective Equipment), Mastery

Summary: Background: High Consequence Infectious Diseases (HCIDs), have the potential to cause pandemics and require particular focus for preparedness due to their high mortality rates. The application of Personal Protective Equipment (PPE) for HCIDs is complex and carries significant risk of Health Care Worker (HCW) contamination if done incorrectly. Previous reviews have reported a lack of information on the nature of training provided and the ideal timing of repeat training to best retain skills. Simulation Based Mastery Learning (SBML) is a methodology for skill acquisition which encompasses deliberate practice and repeated assessment until the learner achieves a pre-set Mastery standard. SBML has been demonstrated to improve competence, skill retention and patient outcomes in other clinical procedures. SBML has not been previously studied or utilised in HCID PPE training. Aim: We aimed to increase the likelihood of safe clinical practice by evidencing that Lothian modified SBML for PPE effectively prepares our priority learners. Methods: A quasi-experimental within group post-test design was used. Learners undertook a modified SBML programme which included two-hour asynchronous and two-hour synchronous components. Findings: 11 learners (10 infectious diseases registrars and 1 infectious diseases consultant) were enrolled in the programme with 8 completing all stages, all of whom achieved the Mastery passing standard. The resources were highly rated by learners with the exemplar videos of skills highlighted as particularly useful. Self-assessed preparedness for each skill increased following pre-learning and synchronous sessions. Conclusion: Modified SBML can be used as an effective methodology for the training and assessment of HCWs in the donning and doffing of HCID PPE

Short-chain fatty acid level and field cancerization show opposing associations with enteroendocrine cell number and neuropilin expression in patients with colorectal adenoma

Abstract Background Previous reports have suggested that the VEGF receptor neuropilin-1 (NRP-1) is expressed in a singly dispersed subpopulation of cells in the normal colonic epithelium, but that expression becomes dysregulated during colorectal carcinogenesis, with higher levels in tumour suggestive of a poor prognosis. We noted that the spatial distribution and morphology if NRP-1 expressing cells resembles that of enteroendocrine cells (EEC) which are altered in response to disease state including cancer and irritable bowel syndrome (IBS). We have shown that NRP-1 is down-regulated by butyrate in colon cancer cell lines in vitro and we hypothesized that butyrate produced in the lumen would have an analogous effect on the colon mucosa in vivo. Therefore we sought to investigate whether NRP-1 is expressed in EEC and how NRP-1 and EEC respond to butyrate and other short-chain fatty acids (SCFA - principally acetate and propionate). Additionally we sought to assess whether there is a field effect around adenomas. Methodology Biopsies were collected at the mid-sigmoid, at the adenoma and at the contralateral wall (field) of 28 subjects during endoscopy. Samples were fixed for IHC and stained for either NRP-1 or for chromogranin A (CgA), a marker of EEC. Stool sampling was undertaken to assess individuals' butyrate, acetate and propionate levels. Result NRP-1 expression was inversely related to SCFA concentration at the colon landmark (mid-sigmoid), but expression was lower and not related to SCFA concentration at the field. Likewise CgA+ cell number was also inversely related to SCFA at the landmark, but was lower and unresponsive at the field. Crypt cellularity was unaltered by field effect. A colocalisation analysis showed only a small subset of NRP-1 localised with CgA. Adenomas showed extensive, weaker staining for NRP-1 which contrastingly correlated positively with butyrate level. Field effects cause this relationship to be lost. Adenoma tissue shows dissociation of the co-regulation of NRP-1 and EEC. Conclusion NRP-1 is inversely associated with levels of butyrate and other SCFA in vivo and is expressed in a subset of CgA expressing cells. EEC number is related to butyrate level in the same way.</p