Development and initial psychometric properties of the Warwick-Edinburgh Mental Wellbeing Scale-Intellectual Disability version.

BACKGROUND: The Warwick-Edinburgh Mental Wellbeing Scale (WEMWBS; Tennant et al., 2007) is yet to be validated in the intellectual disability (ID) population. The aim of this study was to report the development process and assess the psychometric properties of a newly adapted version of the WEMWBS and the Short WEMWBS for individuals with mild to moderate IDs (WEMWBS-ID/SWEMWBS-ID). METHOD: The WEMWBS item wordings and response options were revised by clinicians and researchers expert in the field of ID, and a visual aid was added to the scale. The adapted version was reviewed by 10 individuals with IDs. The measure was administered by researchers online using screenshare, to individuals aged 16+ years with mild to moderate IDs. Data from three UK samples were collated to evaluate the WEMWBS-ID (n = 96). A subsample (n = 22) completed the measure again 1 to 2 weeks later to assess test-retest reliability, and 95 participants additionally completed an adapted version of the adapted Rosenberg Self-Esteem Scale to examine convergent validity. Additional data from a Canadian sample (n = 27) were used to evaluate the SWEMWBS-ID (n = 123). RESULTS: The WEMWBS-ID demonstrated good internal consistency (ω = 0.77-0.87), excellent test-retest reliability [intraclass correlation coefficient (ICC) = .88] and good convergent validity with the self-esteem scale (r = .48-.60) across samples. A confirmatory factor analysis for a single factor model demonstrated an adequate fit. The SWEMWBS-ID showed poor to good internal consistency (ω = 0.36-0.74), moderate test-retest reliability (ICC = .67) and good convergent validity (r = .48-.60) across samples, and a confirmatory factor analysis indicated good model fit for a single factor structure. CONCLUSIONS: The WEMWBS-ID and short version demonstrated promising psychometric properties, when administered virtually by a researcher. Further exploration of the scales with larger, representative samples is warranted.

Key Factors Affecting Reproductive Success of Thoroughbred Mares and Stallions on a Commercial Stud Farm.

To evaluate factors contributing to fertility of thoroughbred mares, data from 3743 oestrous periods of 2385 mares were collected on a large thoroughbred farm in Ireland. Fourteen stallions (mean age 8.3 years; range 4-15 years) had bred 2385 mares (mean age 9.4 years; range 3-24 years). Maiden mares accounted for 12%, mares with a foal at foot for 64%, and barren, slipped or rested mares for 24% of the total. The mean pregnancy rate per cycle was 67.8% (68.6% in year 1 and 66.9% in year 2). Backward stepwise multivariable logistic regression analysis was utilized to develop two models to evaluate mare factors, including mare age, reproductive status, month of foaling, dystocia, month of cover, foal heat, cycle number, treatments, walk-in status and stallion factors including stallion identity, stallion age, shuttle status, time elapsed between covers and high stallion usage on the per cycle pregnancy rate and pregnancy loss. Old age (p < 0.001) and cover within 20 days post-partum (p < 0.003) were associated with lowered pregnancy rates. High mare age (p < 0.05) and barren, slipped or rested reproductive status (p = 0.05) increased the likelihood of pregnancy loss. Uterine inflammation or infection, if appropriately treated, did not affect fertility. Only high usage of stallions (used more than 21 times in previous week) was associated with lowered (p = 0.009) pregnancy rates. However, shuttle stallions were more likely to have increased (p = 0.035) pregnancy survival, perhaps reflecting a bias in stallion selection. In conclusion, mare age exerted the greatest influence on fertility; nonetheless, thoroughbreds can be effectively managed to achieve high reproductive performance in a commercial setting.

Bevacizumab and Combination Chemotherapy in rectal cancer Until Surgery (BACCHUS): a phase II, multicentre, open-label, randomised study of neoadjuvant chemotherapy alone in patients with high-risk cancer of the rectum.

BACKGROUND: In locally advanced rectal cancer (LARC) preoperative chemoradiation (CRT) is the standard of care, but the risk of local recurrence is low with good quality total mesorectal excision (TME), although many still develop metastatic disease. Current challenges in treating rectal cancer include the development of effective organ-preserving approaches and the prevention of subsequent metastatic disease. Neoadjuvant systemic chemotherapy (NACT) alone may reduce local and systemic recurrences, and may be more effective than postoperative treatments which often have poor compliance. Investigation of intensified NACT is warranted to improve outcomes for patients with LARC. The objective is to evaluate feasibility and efficacy of a four-drug regimen containing bevacizumab prior to surgical resection. METHODS/DESIGN: This is a multi-centre, randomized phase II trial. Eligible patients must have histologically confirmed LARC with distal part of the tumour 4-12 cm from anal verge, no metastases, and poor prognostic features on pelvic MRI. Sixty patients will be randomly assigned in a 1:1 ratio to receive folinic acid + flurourcil + oxaliplatin (FOLFOX) + bevacizumab (BVZ) or FOLFOX + irinotecan (FOLFOXIRI) + BVZ, given in 2 weekly cycles for up to 6 cycles prior to TME. Patients stop treatment if they fail to respond after 3 cycles (defined as ≥ 30 % decrease in Standardised Uptake Value (SUV) compared to baseline PET/CT). The primary endpoint is pathological complete response rate. Secondary endpoints include objective response rate, MRI tumour regression grade, involved circumferential resection margin rate, T and N stage downstaging, progression-free survival, disease-free survival, overall survival, local control, 1-year colostomy rate, acute toxicity, compliance to chemotherapy. DISCUSSION: In LARC, a neoadjuvant chemotherapy regimen - if feasible, effective and tolerable would be suitable for testing as the novel arm against the current standards of short course preoperative radiotherapy (SCPRT) and/or fluorouracil (5FU)-based CRT in a future randomised phase III trial. TRIAL REGISTRATION: Clinical trial identifier BACCHUS: NCT01650428.

Hydration and endocrine responses to intravenous fluid and oral glycerol.

Athletes use intravenous (IV) saline in an attempt to maximize rehydration. The diuresis from IV rehydration may be circumvented through the concomitant use of oral glycerol. We examined the effects of rehydrating with differing regimes of oral and IV fluid, with or without oral glycerol, on hydration, urine, and endocrine indices. Nine endurance-trained men were dehydrated by 4% bodyweight, then rehydrated with 150% of the fluid lost via four protocols: (a) oral = oral fluid only; (b) oral glycerol = oral fluid with added glycerol (1.5 g/kg); (c) IV = 50% IV fluid, 50% oral fluid; and (d) IV with oral glycerol = 50% IV fluid, 50% oral fluid with added glycerol (1.5 g/kg), using a randomized, crossover design. They then completed a cycling performance test. Plasma volume restoration was highest in IV with oral glycerol > IV > oral glycerol > oral. Urine volume was reduced in both IV trials compared with oral. IV and IV with oral glycerol resulted in lower aldosterone levels during rehydration and performance, and lower cortisol levels during rehydration. IV with oral glycerol resulted in the greatest fluid retention. In summary, the IV conditions resulted in greater fluid retention compared with oral and lower levels of fluid regulatory and stress hormones compared with both oral conditions.

Abnormalities in collagen composition may contribute to the pathogenesis of hemorrhoids: morphometric analysis.

PURPOSE: While hemorrhoidal disease is common, its etiology remains unclear. It has been postulated that disturbances in collagen lead to reduced connective tissue stability, and in turn to the development of hemorrhoidal disease. We aimed to compare the quality and quantity of collagen in patients with hemorrhoidal disease versus normal controls. METHODS: Specimens from 57 patients with grade III or IV internal hemorrhoids undergoing hemorrhoidectomy between 2006 and 2011 were evaluated. Samples from 20 human cadavers without hemorrhoidal disease served as controls. Quality of collagen was analyzed by collagen I/III ratio, and quantity of collagen was determined by collagen/protein ratio. The study group was subdivided into gender and age subgroups. RESULTS: The male:female ratios in the study and control groups were 30:27 and 10:10, respectively. Median age was significantly less in the study group [46.9 years (range 20-69)] compared to the control group [76 years (range 46-90)] with P < 0.05. Tissues from patients in the study group had significantly lower collagen I/III ratio as compared to the control group (4.4 ± 1.1 vs. 5.5 ± 0.6; P < 0.0001). Nevertheless, despite a trend toward lower collagen/protein ratio in the study group, it did not reach statistical significance (57 ± 42.4 vs. 73 ± 32.5 g/mg; P = 0.167). There was no difference in collagen I/III or collagen/protein ratios among different age groups and genders. CONCLUSIONS: Hemorrhoidal tissues from patients with hemorrhoidal disease appear to have reduced mechanical stability as compared to normal controls.

Action Stations! 100 years of trauma care on maritime and amphibious operations in the Royal Navy.

Over the past century trauma care within the Royal Navy (RN) has evolved; wartime experiences and military medical research have combined to allow significant improvement in the care of casualties. This article describes the key maritime and amphibious operations that have seen the Royal Navy Medical Service (RNMS) deliver high levels of support to wherever the Naval Service has deployed in the last 100 years. Key advancements in which progress has led to improved outcomes for injured personnel are highlighted--the control and treatment of blood loss, wound care, and the prevention and management of organ failure with optimal resuscitation. Historians often point out how slowly military medicine progressed for the first few thousand years of its recorded history, and how quickly it has progressed in the last century. This reflective article will show how the RNMS has been an integral part of that story, and how the lessons learnt by our predecessors have shaped our modern day doctrine surrounding trauma care.

On the fluid dynamics of a laboratory scale single-use stirred bioreactor.

The commercial success of mammalian cell-derived recombinant proteins has fostered an increase in demand for novel single-use bioreactor (SUB) systems that facilitate greater productivity, increased flexibility and reduced costs (Zhang et al., 2010). These systems exhibit fluid flow regimes unlike those encountered in traditional glass/stainless steel bioreactors because of the way in which they are designed. With such disparate hydrodynamic environments between SUBs currently on the market, traditional scale-up approaches applied to stirred tanks should be revised. One such SUB is the Mobius® 3 L CellReady, which consists of an upward-pumping marine scoping impeller. This work represents the first experimental study of the flow within the CellReady using a Particle Image Velocimetry (PIV) approach, combined with a biological study into the impact of these fluid dynamic characteristics on cell culture performance. The PIV study was conducted within the actual vessel, rather than using a purpose-built mimic. PIV measurements conveyed a degree of fluid compartmentalisation resulting from the up-pumping impeller. Both impeller tip speed and fluid working volume had an impact upon the fluid velocities and spatial distribution of turbulence within the vessel. Cell cultures were conducted using the GS-CHO cell-line (Lonza) producing an IgG4 antibody. Disparity in cellular growth and viability throughout the range of operating conditions used (80-350 rpm and 1-2.4 L working volume) was not substantial, although a significant reduction in recombinant protein productivity was found at 350 rpm and 1 L working volume (corresponding to the highest Reynolds number tested in this work). The study shows promise in the use of PIV to improve understanding of the hydrodynamic environment within individual SUBs and allows identification of the critical hydrodynamic parameters under the different flow regimes for compatibility and scalability across the range of bioreactor platforms.

A modern-day solution to a 100-year-old problem: the use of a Bespoke Off-loading Brace in the rehabilitation of 'Deck-Slap' and other high-energy lower limb injuries.

'Deck-Slap' is an injury pattern first described at the Battle of Jutland; it is still relevant today, with anti-vehicle mines a significant threat to Coalition troops. The effect of a device exploding beneath a vehicle produces a wave of high energy that is rapidly transmitted through the steel floor; this causes significant axial loading of lower limbs often resulting in severe fractures (notably of the calcaneum). Recent advancements in orthopaedic surgery have allowed for limbs that were destined for immediate amputation following significant trauma to be salvaged. However, despite intense rehabilitation, many of these salvaged limbs have subsequently gone on to delayed amputation, as functional outcomes are often poor. Technologically advanced prosthetic devices are available that afford good quality of life and allow for increased activity levels; these devices are, however, expensive to procure and maintain. This report describes a United Kingdom (UK) Armed Forces soldier who suffered a typical 'deck-slap' injury in Afghanistan with subsequent limb salvage. The use of the Bespoke Off-loading Brace (BOB) is discussed. The results presented here indicate that the biomechanical function of a patient with this type of injury improves when wearing the BOB. Further studies are needed to assess long-term clinical outcomes and the functional benefit of the device as a viable and cost-effective alternative to delayed limb amputation.

Cross-architecture tuning of silicon and SiGe-based quantum devices using machine learning.

The potential of Si and SiGe-based devices for the scaling of quantum circuits is tainted by device variability. Each device needs to be tuned to operation conditions and each device realisation requires a different tuning protocol. We demonstrate that it is possible to automate the tuning of a 4-gate Si FinFET, a 5-gate GeSi nanowire and a 7-gate Ge/SiGe heterostructure double quantum dot device from scratch with the same algorithm. We achieve tuning times of 30, 10, and 92 min, respectively. The algorithm also provides insight into the parameter space landscape for each of these devices, allowing for the characterization of the regions where double quantum dot regimes are found. These results show that overarching solutions for the tuning of quantum devices are enabled by machine learning.

Sebaceous cysts with unpleasant twists: cutaneous myiasis with Dermatobia hominis.

Dermatobia hominis (human Bot fly) causes furuncular myiasis (larval infection) in Central and South America. This report describes a case in a member of the UK Armed Forces who had recently taken part in an overseas training exercise in Belize. The importance of clinical history (including travel history) is highlighted. We also describe the outcomes of conservative treatment and surgical intervention for separate lesions in the same patient.

Development of optimised tissue-equivalent materials for proton therapy.

Objective. In proton therapy there is a need for proton optimised tissue-equivalent materials as existing phantom materials can produce large uncertainties in the determination of absorbed dose and range measurements. The aim of this work is to develop and characterise optimised tissue-equivalent materials for proton therapy.Approach. A mathematical model was developed to enable the formulation of epoxy-resin based tissue-equivalent materials that are optimised for all relevant interactions of protons with matter, as well as photon interactions, which play a role in the acquisition of CT numbers. This model developed formulations for vertebra bone- and skeletal muscle-equivalent plastic materials. The tissue equivalence of these new materials and commercial bone- and muscle-equivalent plastic materials were theoretical compared against biological tissue compositions. The new materials were manufactured and characterised by their mass density, relative stopping power (RSP) measurements, and CT scans to evaluate their tissue-equivalence.Main results. Results showed that existing tissue-equivalent materials can produce large uncertainties in proton therapy dosimetry. In particular commercial bone materials showed to have a relative difference up to 8% for range. On the contrary, the best optimised formulations were shown to mimic their target human tissues within 1%-2% for the mass density and RSP. Furthermore, their CT-predicted RSP agreed within 1%-2% of the experimental RSP, confirming their suitability as clinical phantom materials.Significance. We have developed a tool for the formulation of tissue-equivalent materials optimised for proton dosimetry. Our model has enabled the development of proton optimised tissue-equivalent materials which perform better than existing tissue-equivalent materials. These new materials will enable the advancement of clinical proton phantoms for accurate proton dosimetry.

The feasibility and impact of implementing a computer-guided consultation to target health inequality in Asthma.

Greater Manchester has a greater prevalence and worse asthma outcomes than the national average. This study aims to evaluate a digital approach to primary care asthma management and in particular the initial impact of implementing Clinical Decision Support System software in the form of a computer-guided consultation (CGC) in the setting of primary care asthma reviews in deprived areas of Greater Manchester. The CGC (LungHealth Ltd) is an intelligent decision support system ensuring accurate guideline-based staging of asthma and assessment of asthma control with the software subsequently prompting guideline-standard management. Patients on asthma registers in Greater Manchester Primary Care Networks were identified and underwent remote review by nursing staff using the CGC linked directly to the GP clinical system. Three-hundred thirty-eight patients (mean age 59 (SD 17) years; 60% Female) were reviewed. The CGC reported the patient's asthma control to be "Good" in 22%, "Partial" in 6% and "Poor" in 72%. ACT scores were significantly higher in those patients exhibiting "Good" and "Partial" control when compared to those with "Poor" control. The number of steroid courses and hospital admissions in the previous 12 months was significantly lower in those patients exhibiting "Good" and "Partial" control when compared to those with "Poor" control. Nineteen percent were found not to have a personalised asthma management plan during CGC review, which was alerted by the CGC and subsequently, all but 3 patients had this created on review completion (McNemar's test; p < 0.001). 5% were found not to have been prescribed regular inhaled steroid therapy resulting in the operator being alerted by the CGC in all cases. Overall, 44% underwent alteration in asthma therapy following the CGC review with 82% of these representing treatment escalation. An end-to-end digital service solution is feasible for Asthma within primary care and the utilisation of a CGC when conducting primary care asthma reviews increases implementation of guideline-level management thus addressing healthcare inequality while enabling identification of "high risk" asthma patients and guiding appropriate therapy escalation and de-escalation.

A randomised study evaluating the use of pyridoxine to avoid capecitabine dose modifications.

BACKGROUND: Pyridoxine is frequently used to treat capecitabine-induced hand-foot syndrome (HFS), although the evidence of benefit is lacking. We performed a randomised placebo-controlled trial to determine whether pyridoxine could avoid the need for capecitabine dose modifications and improve outcomes. METHODS: A total of 106 patients planned for palliative single-agent capecitabine (53 in each arm, 65%/35% colorectal/breast cancer) were randomised to receive either concomitant pyridoxine (50 mg po) or matching placebo three times daily. RESULTS: Compared with placebo, pyridoxine use was associated with an increased rate of avoiding capecitabine dose modifications (37% vs 23%, relative risk 0.59, 95% CI 0.29, 1.20, P=0.15) and fewer grade 3/4 HFS-related adverse events (9% vs 17%, odds ratio 0.51, 95% CI 0.15-1.6, P=0.26). Use of pyridoxine did not improve response rate or progression-free survival. CONCLUSION: Pyridoxine may reduce the need for capecitabine dose modifications and the incidence of severe HFS, but does not impact on antitumour effect.

A single-centre experience of chemoradiotherapy for rectal cancer: is there potential for nonoperative management?

AIM: The aim of the study was to assess the outcome of patients who received chemoradiotherapy (CRT) for locally advanced rectal cancer, specifically those with complete clinical response (CCR) and who were then managed nonoperatively with a 'Watch and Wait' follow-up protocol. METHOD: A retrospective study was carried out of patients undergoing preoperative CRT for rectal cancer, conducted in a district general hospital managing rectal cancer through the multidisciplinary team process. RESULTS: Forty-nine patients received preoperative CRT over a 5-year period (2004-2009). Twelve (24%) were considered potentially to have had a complete response on MRI. Of these, six subsequently had clinical evidence of residual disease, leading to surgery (mean time to surgery, 24 weeks; range, 12-36 weeks). The remaining six had CCR, avoiding surgery (mean follow up, 26 months; range, 12-45 months), with all six patients disease free to date. A further six patients had complete pathological response (CPR) following surgery after comprehensive histopathological assessment of the specimen. CONCLUSION: In this consecutive series of patients with locally advanced rectal cancer treated with CRT, 12% demonstrated a CCR and have been actively managed conservatively, thereby avoiding surgery. With further improvements in diagnostic assessment of response to CRT, this figure may rise.

Persistent fatigue in young athletes: measuring the clinical course and identifying variables affecting clinical recovery.

The objective of this paper is to measure the clinical course (months) in young athletes with persistent fatigue and to identify any covariates affecting the duration of recovery. This was a prospective longitudinal study of 68 athletes; 87% were elite (42 males, 26 females), aged 20.5±3.74 years (SD), who presented with the symptom of persistent fatigue. The collective duration to full clinical recovery was estimated using Kaplan-Meier product-limit curves, and covariates associated with prolonging recovery were identified from Cox proportional hazard models. The median recovery was 5 months (range 1-60 months). The range of presenting symptom duration was 0.5-36 months. The covariates identified were an increased duration of presenting symptoms [hazard ratio (HR), 1.06; 95% confidence interval (CI), 1.02-1.12; P=0.005] and the response of serum cortisol concentration to a standard exercise challenge (HR, 1.92; 95% CI, 1.09-3.38; P=0.03). Delay in recovery was not associated with categories of fatigue that included medical, training-related diagnoses, or other causes. In conclusion, the fatigued athlete represents a significant clinical problem with a median recovery of 5 months, whose collective clinical course to recovery can be estimated by Kaplan-Meier curves and appears to be a continuum.

The changing face of rhinology in the NHS: a study of septoplasty, septorhinoplasty and rhinoplasty hospital episode statistics.

INTRODUCTION: In 2011, septorhinoplasty and rhinoplasty were reclassified as procedures of limited clinical value in the NHS. The criteria for funding these operations varies across England. We used hospital episode statistics and freedom of information requests to review the total number of rhinology procedures performed across the previous decade, looking at trends in practice related to time, demographics and commissioning policy. MATERIALS AND METHODS: Hospital episode statistics for 2012-2019 were used to calculate the number of septoplasty, septorhinoplasty, rhinoplasty and reduction rhinoplasty procedures performed in children and adults. Freedom of information requests were also made to all clinical commissioning groups in England asking for number of procedures performed and number of individual funding requests made. RESULTS: A total of 158,031 procedures were performed over this period; the majority were in adult (99.0%) men (65.7%). Septoplasty was the most frequently performed operation; however, the total numbers declined by 5.4% over this period. There was a yearly reduction in the overall number of septorhinoplasty, rhinoplasty and reduction rhinoplasty operations. Four clinical commissioning groups provided a detailed breakdown of data by year and procedure. Those that required individual funding requests for all cases saw septorhinoplasty numbers fall by 81% and 75% over the period. Those that did not, saw numbers increase or remain the same. CONCLUSIONS: We found an overall year-on-year reduction in the number of rhinology operations being performed in the NHS, but variation in trends between different clinical commissioning groups. A reduction in operative activity likely represents the effect of underlying restrictions on commissioning rather than reduced clinical need.

Experiences in academic publication among ENT trainees in the UK: results from a national survey.

OBJECTIVE: This study aimed to provide an objective means of identifying patterns in academic publication among ENT trainees during their higher surgical training. METHOD: A cross-sectional survey was distributed to ENT higher surgical trainees. RESULTS: A total of 153 ENT specialty trainees participated, giving a response rate of 46.5 per cent. Across all years of training, the mean number of first author publications was three and the mean number of non-first author publications was two. For trainees at specialty trainee year 8 level, these figures were nine and five, respectively. Participants with doctoral degrees and those in academic programmes published more papers but the mean difference was only significant for the doctoral subgroup (p < 0.0001). Those with additional undergraduate degrees and those in less than full-time training had an overall lower number of publications. CONCLUSION: Participants in the current survey achieved a higher average number of academic publications than is presently required to successfully complete higher surgical training in ENT. It is hoped that these results act as a guide for trainees planning the research component of their training to ensure that they remain competitive at consultant interview.

'There's a frog in my throat': bilateral prolapsing lung apices presenting as a neck lump.

This case report discusses an unusual presentation of a voluntarily produced neck mass, caused by the rare case of lung herniation. Lung herniation is associated with increased intrathoracic pressure that can be caused by chronic chough, straining and continuous positive airway pressure ventilation. An association with Ehlers-Danlos syndrome 1 also exists. We present a case of lung herniation that was multifactorial in nature and was identified at a head and neck clinic. The female patient presented with a voluntarily expandable anterior neck mass on Valsalva manoeuvre. Computed tomography imaging with and without Valsalva manoeuvre demonstrated bilateral anterior lung herniation and findings of spinal spondylosis.