Using the Traditional Ex Vivo Whole Blood Model to Discriminate Bacteria by Their Inducible Host Responses.

Whole blood models are rapid and versatile for determining immune responses to inflammatory and infectious stimuli, but they have not been used for bacterial discrimination. Staphylococcus aureus, S. epidermidis and Escherichia coli are the most common causes of invasive disease, and rapid testing strategies utilising host responses remain elusive. Currently, immune responses can only discriminate between bacterial 'domains' (fungi, bacteria and viruses), and very few studies can use immune responses to discriminate bacteria at the species and strain level. Here, whole blood was used to investigate the relationship between host responses and bacterial strains. Results confirmed unique temporal profiles for the 10 parameters studied: IL-6, MIP-1α, MIP-3α, IL-10, resistin, phagocytosis, S100A8, S100A8/A9, C5a and TF3. Pairwise analysis confirmed that IL-6, resistin, phagocytosis, C5a and S100A8/A9 could be used in a discrimination scheme to identify to the strain level. Linear discriminant analysis (LDA) confirmed that (i) IL-6, MIP-3α and TF3 could predict genera with 95% accuracy; (ii) IL-6, phagocytosis, resistin and TF3 could predict species at 90% accuracy and (iii) phagocytosis, S100A8 and IL-10 predicted strain at 40% accuracy. These data are important because they confirm the proof of concept that host biomarker panels could be used to identify bacterial pathogens.

Risk factors for burn contractures: A cross-sectional study in a lower income country.

Risk factors for burn contractures require further study, especially in low and middle-income countries (LMICs); existing research has been predominantly conducted in high income countries (HICs). This study aimed to identify risk factors for burn contractures of major joints in a low-income setting. Potential risk factors (n = 104) for burn contracture were identified from the literature and a survey of clinicians with extensive experience in low and middle-income countries (LMIC). An observational cross-sectional study of adult burn survivors was undertaken in Bangladesh to evaluate as many of these risk factors as were feasible against contracture presence and severity. Forty-eight potential risk factors were examined in 48 adult patients with 126 major joints at risk (median 3 per participant) at a median of 2.5 years after burn injury. Contractures were present in 77% of participants and 52% of joints overall. Contracture severity was determined by measurement of loss of movement at all joints at risk. Person level risk factors were defined as those that were common to all joints at risk for the participant and only documented once, whilst joint level risk factors were documented for each of the participant's included joints at risk. Person level risk factors which were significantly correlated with loss of range of movement (ROM) included employment status, full thickness burns, refusal of skin graft, discharged against medical advice, low frequency of follow up and lack of awareness of contracture development. Significant joint level risk factors for loss of ROM included anatomical location, non-grafted burns, and lack of pressure therapy. This study has examined the largest number of potential contracture risk factors in an LMIC setting to date. A key finding was that risk factors for contracture in low-income settings may differ substantially from those seen in high income countries, which has implications for effective prevention strategies in these countries. Better whole person and joint outcome measures are required for accurate determination of risk factors for burn contracture. Recommendations for planning and reporting on future contracture risk factor studies are made.

Embedding retrieval practice in undergraduate biochemistry teaching using PeerWise.

Retrieval practice is an evidence-based approach to teaching; here, we evaluate the use of PeerWise for embedding retrieval practice into summative assessment. PeerWise allows anonymous authoring, sharing, answering, rating, and feedback on peer-authored multiple choice questions. PeerWise was embedded as a summative assessment in a large first-year introductory biochemistry module. Engagement with five aspects of the tool was evaluated against student performance in coursework, exam, and overall module outcome. Results indicated a weak-to-moderate positive but significant correlation between engagement with PeerWise and assessment performance. Student feedback showed PeerWise had a polarizing effect; the majority recognized the benefits as a learning and revision tool, but a minority strongly disliked it, complaining of a lack of academic moderation and irrelevant questions unrelated to the module. PeerWise can be considered a helpful learning tool for some students and a means of embedding retrieval practice into summative assessment.

The association of anxiety disorders and depression with facial scarring: population-based, data linkage, matched cohort analysis of 358 158 patients.

BACKGROUND: Estimates suggest that 1 in 100 people in the UK live with facial scarring. Despite this incidence, psychological support is limited. AIMS: The aim of this study was to strengthen the case for improving such support by determining the incidence and risk factors for anxiety and depression disorders in patients with facial scarring. METHOD: A matched cohort study was performed. Patients were identified via secondary care data sources, using clinical codes for conditions resulting in facial scarring. A diagnosis of anxiety or depression was determined by linkage with the patient's primary care general practice data. Incidence was calculated per 1000 person-years at risk (PYAR). Logistic regression was used to determine risk factors. RESULTS: Between 2009 and 2018, 179 079 patients met the study criteria and were identified as having a facial scar, and matched to 179 079 controls. The incidence of anxiety in the facial scarring group was 10.05 per 1000 PYAR compared with 7.48 per 1000 PYAR for controls. The incidence of depression in the facial scarring group was 16.28 per 1000 PYAR compared with 9.56 per 1000 PYAR for controls. Age at the time of scarring, previous history of anxiety or depression, female gender, socioeconomic status and classification of scarring increased the risk of both anxiety disorders and depression. CONCLUSIONS: There is a high burden of anxiety disorders and depression in this patient group. Risk of these mental health disorders is very much determined by factors apparent at the time of injury, supporting the need for psychological support.

In vitro hemolytic performance of the Realheart® V11C TAH prototype with porcine blood.

BACKGROUND: Hemolysis testing of new devices to treat heart failure is a regulatory requirement. The ASTM F1841-97 standard for hemolysis testing was developed for continuous flow pumps and does not specify test rig design. When research groups use different methodologies, results are difficult to compare. Pulsatile flow pump rigs require compliance chambers, and thus, the Aachen rig (Gräf et al) was developed for the pulsatile Reinheart TAH. The study objective was to use this rig to test the early Realheart TAH prototype V11C hemolysis performance compared to literature. METHODS: The experimental control was the continuous flow pump BPX-80 (Medtronic) and pooled heparinized porcine blood was used. RESULTS: The mgNIH of BPX-80 and V11C was 5.42 ± 1.47 and 25.20 ± 5.46 mg/100 L, respectively. The NIH ratio of V11C over BPX-80 was 5.5. CONCLUSION: The absolute and the relative hemolysis of the V11C are lower compared to both the large and small Reinheart TAH devices published values. Pulsatile pumps create more hemolysis in the Aachen rig, and it is not known if this is because how the rig handles pulsatile flow or due to the devices. Future studies will, therefore, use a pulsatile pump such as the SynCardia as clinical comparator and human blood to test the performance of future Realheart TAH prototypes.

Identifying unmet antithrombotic therapeutic need, and implications for stroke and systemic embolism in atrial fibrillation patients: a population-scale longitudinal study.

Aims: Guidelines recommend anticoagulation (AC) in atrial fibrillation (AF) to reduce stroke and systemic embolism (SSE) risk; however, implementation has been slow across many populations. This study aimed to quantify the potential impact of changing prevalence of AF, associated risk, and AC prescribing on SSE hospitalizations and death. Methods and results: We evaluated temporal trends of AF, CHA2DS2-VASc, antithrombotic prescriptions, SSE hospitalizations, death, and their associations between 2012 and 2018 in a longitudinal cohort of AF patients in Wales UK. Multi-state Markov models were used to estimate expected SSE rates given the AC coverage, adjusting for CHA2DS2-VASc scores. SSE rates were modelled for various past and future AC scenarios. A total of 107 137 AF patients were evaluated (mean age = 74 years, 45% female). AF prevalence increased from 1.75 to 2.22% (P-value <0.001). SSE hospitalizations decreased by 18% (2.34-1.92%, P-value <0.001). Increased AC coverage from 50 to 70% was associated with a 37% lower SSE rate, after adjustment for individual time-dependent CHA2DS2VASc scores. The observed AC increase accounted for approximately 80 fewer SSE hospitalizations per 100 000/year. If 90% AC coverage had been achieved since 2012, an estimated 279 SSE per 100 000/year may have been prevented. Our model also predicts that improving AC coverage to 90% over the next 9 years could reduce annual SSE rates by 9%. Conclusion: We quantified the relationship between observed AC coverage, estimating the potential impact of variation in the timing of large-scale implementation. These data emphasize the importance of timely implementation and the considerable opportunity to improve clinical outcomes in the Wales-AF population.

A pilot study investigating the effects of a manuka honey sinus rinse compared to a standard sinus rinse on sino-nasal outcome test scores in cystic fibrosis patients.

BACKGROUND: People with cystic fibrosis (CF) are prone to bacterial respiratory infections; these are often antibiotic resistant, are difficult to treat, and impact on the quality of life and lung function. The upper respiratory tract can act as a reservoir for these pathogens, and as part of clinical care, sinus rinses are used to alleviate symptoms in the upper airway. We have developed a sinus rinse containing manuka honey, to identify whether it can help improve symptoms or reduce the bacterial load. METHODS: We will undertake a randomised controlled trial where 30 adults with CF will be recruited and randomised to either the control or intervention group. Both groups will follow a sinus rinse protocol for 30 days (± 7 days); the control group will use the standard of care rinse, and the intervention group will use a manuka honey rinse. Both groups will provide samples at day 0 and day 30. The primary outcome measure will be a change in the 22-item Sino-Nasal Outcome Test (SNOT-22) score. Secondary outcomes will include changes to quality of life (questionnaire), bacterial load/community composition, and sputum viscosity. DISCUSSION: This trial will look at the use of a manuka honey-infused sinus rinse solution on patients diagnosed with cystic fibrosis (CF) suffering with sinusitis; it will allow us to determine the efficacy of the manuka honey sinus rinse compared to standard rinse and will allow us to determine if molecular bacterial diversity analysis will provide in-depth information beyond the usual conventional microbiological. It will allow us to determine the feasibility of recruiting participants to this type of trial, allow us to check participant compliance with the protocol, and inform future studies. TRIAL REGISTRATION: Approval was obtained from the Research Ethics Committee Wales REC7 reference 18/WA/0319. Results of this study will be published at international conferences and in peer-reviewed journals; they will also be presented to the relevant stakeholders and research networks. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Identifier NCT04589897 (retrospectively registered).

Functional outcome and patient satisfaction with a 'self-care' protocol for minimally displaced distal radius fractures : a service evaluation.

AIMS: We introduced a self-care pathway for minimally displaced distal radius fractures, which involved the patient being discharged from a Virtual Fracture Clinic (VFC) without a physical review and being provided with written instructions on how to remove their own cast or splint at home, plus advice on exercises and return to function. METHODS: All patients managed via this protocol between March and October 2020 were contacted by a medical secretary at a minimum of six months post-injury. The patients were asked to complete the Patient-Rated Wrist Evaluation (PRWE), a satisfaction questionnaire, advise if they had required surgery and/or contacted any health professional, and were also asked for any recommendations on how to improve the service. A review with a hand surgeon was organized if required, and a cost analysis was also conducted. RESULTS: Overall 71/101 patients completed the telephone consultation; no patients required surgery, and the mean and median PRWE scores were 23.9/100 (SD 24.9) and 17.0/100 (interquartile range (IQR) 0 to 40), respectively. Mean patient satisfaction with treatment was 34.3/40 (SD 9.2), and 65 patients (92%) were satisfied or highly satisfied. In total there were 16 contact calls, 12 requests for a consultant review, no formal complaints, and 15 minor adjustment suggestions to improve patient experience. A relationship was found between intra-articular injuries and lower patient satisfaction scores (p = 0.025), however no relationship was found between PRWE scores and the nature of the fracture. Also, no relationship was found between the type of immobilization and the functional outcome or patient satisfaction. Cost analysis of the self-care pathway V traditional pathway showed a cost savings of over £13,500 per year with the new self-care model compared to the traditional model. CONCLUSION: Our study supports a VFC self-care pathway for patients with minimally displaced distal radius fractures. The pathway provides a good level of patient satisfaction and function. To improve the service, we will make minor amendments to our patient information sheet.Cite this article: Bone Jt Open 2022;3(9):726-732.

Measuring recovery after open lower limb fractures: combined objective functional tests and global perceived recovery outperform narrower metrics and a standard generic patient reported outcome measure.

BACKGROUND: Open lower limb fractures are serious injuries requiring combined ortho-plastic surgery and have significantly worse outcomes than similar closed fractures. There is little objective published data to determine which functional outcome measures best reflect progress or completeness of physical recovery. Our hypothesis was that objective measures combining strength, mobility and balance would better reflect recovery than isolated parameters (e.g. range of motion ROM) and would compare well to patients' perceived recovery. METHODS: Adult open lower limb fracture patients were reviewed 6 and 12 weeks, 6, 9 and 12 months post-injury. The mechanism, injury pattern, age, gender and treatment were recorded. Isolated parameter objective functional outcome measures (OFOMs) (ROM and MRC strength grade) were compared to combined OFOMs (timed up and go, comfortable gait speed and fast gait speed, Edgren Side Step Test (TUAG, CGS, FGS, ESST) and Single Leg balance. Patient reported outcomes were recorded (Global Perceived Effect (GPE) score and Disability Rating Index (DRI)). Statistical analysis used non-parametric tests (e.g. Spearman correlation) compared each with time since injury. RESULTS: Sixty-eight patients (54 male) with a median age of 45(20-75) years. Of the 19 isolated OFOMs, only knee flexion and ankle plantar flexion ROM and strength improved with time (Spearman correlation p = 0.042, 0.008, 0.032, 0.036 respectively). TUAG, ESST, CGS, FGS and GPE scores showed significant improvement (Spearman correlation p < 0.001). Patients' estimation of recovery paralleled these measures (Spearman correlation p < 0.001) with all but 2 patients achieving the minimum clinical important difference in DRI by 12 months compared to baseline. However, the GPE score had a higher proportion of improving responses than DRI at each time-point. DISCUSSION: Functional recovery is a key determinant in patients returning to work, providing for themselves and their family or resuming independent living for older patients. This study has demonstrated time-related improvements in combined OFOMs measuring mobility, strength, agility and balance paralleling patients' perception of recovery in the 12 months after open lower limb fractures. Over the same time-frame, the simple GPE score compared favourably with the DRI. Such parameters could become part of a defined core outcomes set. Focussing rehabilitation towards these combined OFOMs may help hasten recovery. TRIAL REGISTRATION: South West Wales REC 06/WMW02/10).

Temporal Changes in Patient-Matched Staphylococcus epidermidis Isolates from Infections: towards Defining a 'True' Persistent Infection.

Staphylococcus epidermidis is found naturally on the skin but is a common cause of persistent orthopaedic device-related infections (ODRIs). This study used a pan-genome and gene-by-gene approach to analyse the clonality of whole genome sequences (WGS) of 115 S. epidermidis isolates from 55 patients with persistent ODRIs. Analysis of the 522 gene core genome revealed that the isolates clustered into three clades, and MLST analysis showed that 83% of the isolates belonged to clonal complex 2 (CC2). Analysis also found 13 isolate pairs had different MLST types and less than 70% similarity within the genes; hence, these were defined as re-infection by a different S. epidermidis strain. Comparison of allelic diversity in the remaining 102 isolates (49 patients) revealed that 6 patients had microevolved infections (>7 allele differences), and only 37 patients (77 isolates) had a 'true' persistent infection. Analysis of the core genomes of isolate pairs from 37 patients found 110/841 genes had variations; mainly in metabolism associated genes. The accessory genome consisted of 2936 genes; with an average size of 1515 genes. To conclude, this study demonstrates the advantage of using WGS for identifying the accuracy of a persistent infection diagnosis. Hence, persistent infections can be defined as 'true' persistent infections if the core genome of paired isolates has ≤7 allele differences; microevolved persistent infection if the paired isolates have >7 allele differences but same MLST type; and polyclonal if they are the same species but a different MLST type.

A Web-Delivered Acceptance and Commitment Therapy Intervention With Email Reminders to Enhance Subjective Well-Being and Encourage Engagement With Lifestyle Behavior Change in Health Care Staff: Randomized Cluster Feasibility Stud.

BACKGROUND: Poor mental health and emotional well-being can negatively impact ability to engage in healthy lifestyle behavior change. Health care staff have higher rates of sickness and absence than other public sector staff, which has implications at both individual and societal levels. Individual efforts to self-manage health and well-being which add to the UK mental health prevention agenda need to be supported. OBJECTIVE: The objective of this study was to establish the feasibility and acceptability of the inclusion of a self-guided, automated, web-based acceptance and commitment therapy intervention in an existing health promotion program, to improve subjective well-being and encourage engagement with lifestyle behavior change. METHODS: For this 12-week, 4-armed, randomized controlled cluster feasibility study, we recruited participants offline and randomly allocated them to 1 of 3 intervention arms or control (no well-being intervention) using an automated web-based allocation procedure. Eligibility criteria were current health care staff in 1 Welsh health board, age≥18 years, ability to read English, and ability to provide consent. The primary researcher was blinded to cluster allocation. Feasibility outcomes were randomization procedure, acceptance of intervention, and adherence to and engagement with the wider program. We evaluated health and well-being data via self-assessment at 2 time points, registration and postintervention, using the 14-item Warwick-Edinburgh Mental Well-Being Scale, the 4-item Patient Health Questionnaire, and the 7-item Acceptance and Action Questionnaire-Revised. RESULTS: Of 124 participants who provided consent and were randomly allocated, 103 completed full registration and engaged with the program. Most participants (76/103) enrolled in at least one health behavior change module, and 43% (41/96) of those randomly allocated to an intervention arm enrolled in the well-being module. Adherence and engagement was low (7/103, 6.8%), but qualitative feedback was positive. CONCLUSIONS: The procedure and randomization process proved feasible, and the addition of the well-being module proved acceptable to health care staff. However, participant engagement was limited, and no one completed the full 12-week program. User feedback should be used to develop the intervention to address poor engagement. Effectiveness should then be evaluated in a full-scale randomized controlled trial, which would be feasible with additional recruitment. TRIAL REGISTRATION: International Standard Randomised Controlled Trial Number (ISRCTN) 50074817; http://www.isrctn.com/ISRCTN50074817.

Mechanical assist devices for acute cardiogenic shock.

BACKGROUND: Cardiogenic shock (CS) is a state of critical end-organ hypoperfusion due to a primary cardiac disorder. For people with refractory CS despite maximal vasopressors, inotropic support and intra-aortic balloon pump, mortality approaches 100%. Mechanical assist devices provide mechanical circulatory support (MCS) which has the ability to maintain vital organ perfusion, to unload the failing ventricle thus reduce intracardiac filling pressures which reduces pulmonary congestion, myocardial wall stress and myocardial oxygen consumption. This has been hypothesised to allow time for myocardial recovery (bridge to recovery) or allow time to come to a decision as to whether the person is a candidate for a longer-term ventricular assist device (VAD) either as a bridge to heart transplantation or as a destination therapy with a long-term VAD. OBJECTIVES: To assess whether mechanical assist devices improve survival in people with acute cardiogenic shock. SEARCH METHODS: We searched CENTRAL, MEDLINE (Ovid), Embase (Ovid) and Web of Science Core Collection in November 2019. In addition, we searched three trials registers in August 2019. We scanned reference lists and contacted experts in the field to obtain further information. There were no language restrictions. SELECTION CRITERIA: Randomised controlled trials on people with acute CS comparing mechanical assist devices with best current intensive care management, including intra-aortic balloon pump and inotropic support. DATA COLLECTION AND ANALYSIS: We performed data collection and analysis according to the published protocol. Primary outcomes were survival to discharge, 30 days, 1 year and secondary outcomes included, quality of life, major adverse cardiovascular events (30 days/end of follow-up), dialysis-dependent (30 days/end of follow-up), length of hospital stay and length of intensive care unit stay and major adverse events. We used the five GRADE considerations (study limitations, consistency of effect, imprecision, indirectness, and publication bias) to assess the quality of a body of evidence as it relates to the studies which contribute data to the meta-analyses for the prespecified outcomes Summary statistics for the primary endpoints were risk ratios (RR), hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CIs). MAIN RESULTS: The search identified five studies from 4534 original citations reviewed. Two studies included acute CS of all causes randomised to treatment using TandemHeart percutaneous VAD and three studies included people with CS secondary to acute myocardial infarction who were randomised to Impella CP or best medical management. Meta-analysis was performed only to assess the 30-day survival as there were insufficient data to perform any further meta-analyses. The results from the five studies with 162 participants showed mechanical assist devices may have little or no effect on 30-day survival (RR of 1.01 95% CI 0.76 to 1.35) but the evidence is very uncertain. Complications such as sepsis, thromboembolic phenomena, bleeding and major adverse cardiovascular events were not infrequent in both the MAD and control group across the studies, but these could not be pooled due to inconsistencies in adverse event definitions and reporting. We identified four randomised control trials assessing mechanical assist devices in acute CS that are currently ongoing. AUTHORS' CONCLUSIONS: There is no evidence from this review of a benefit from MCS in improving survival for people with acute CS. Further use of the technology, risk stratification and optimising the use protocols have been highlighted as potential reasons for lack of benefit and are being addressed in the current ongoing clinical trials.

A Comparison of Improvised and Commercially Available Point-of-Wounding Tourniquets in Simulated Traumatic Amputation with Catastrophic Hemorrhage.

INTRODUCTION: Catastrophic hemorrhage is the leading cause of preventable trauma deaths in the military and civilian populations. The use of tourniquets by first responders (medical and nonmedically trained) is supported and has the potential to save lives if applied correctly. AIMS: We sought to examine the use of 5 tourniquets: 1 improvised and 4 commercially available tourniquets to investigate the time taken to stop simulated bleeding and to secure the device; evidence of rebleeding when the "blood pressure" was restored and to gain qualitative feedback on their application. MATERIALS AND METHODS: Four commercially available tourniquets (Combat Application Tourniquet [C-A-T], Special Operations Forces Tactical Tourniquet - Wide (SOFTT-W), stretch, wrap, and tuck tourniquet [SWAT-T], and the Tourni-key) and an improvised tourniquet (tie & wooden spoon) were tested on a complex silicone simulation model used to replicate catastrophic hemorrhage from a blast injury with above traumatic knee amputation (SAM 4.1 Trauma Simulation Ltd, UK). To limit the user variability, the same investigator applied each tourniquet and each was tested 3 times. No ethical approval was required to conduct this study. RESULTS: None of the devices took longer than 1 minute to secure. The C-A-T and SOFTT-W were quickest to occlude and secure. Although the Tourni-key took longer statistically, this was unlikely to be a clinically important difference. Compared to the others, the SOFTT-W rebled on 2 out of 3 applications. The improvised tourniquet had an obvious ligature effect because of its narrowness, followed by the Tourni-key. This effect was least evident with the SWAT-T; however, particular care was needed to ensure it was safely secured as it was slippery when wet. CONCLUSIONS: All tourniquets tested were effective and swift to apply. The Tourni-key's antipinch card seems helpful in reducing local pain under the windlass. Reinspection for rebleeding is important and should be routinely performed irrespective of the device. The width of the SWAT-T may be beneficial, thereby, reducing the risk of crush injury.

In Vitro Benchmarking Study of Ventricular Assist Devices in Current Clinical Use.

BACKGROUND: Left ventricular assist devices (LVADs) offer live-saving therapy to transplant-ineligible heart failure patients. A major limitation of the technology includes pump thrombosis, bleeding, and recurrent infection that prove difficult to predict from in vivo animal testing. Shear stress introduced by the LVAD affects more than just hemolysis because platelets, leukocytes, and plasma proteins all contribute to the propensity for complications. It is important to assess overall damage by a new device against a baseline as early as possible in the development process so that design iterations can be made if required. METHODS: Explanted VADs currently in clinical use (HeartMate 2 and HVAD) were carefully cleaned, inspected, and run at 5 L/min and pressure at 100 mmHg in a standard 500 mL mock circulatory loop using bovine blood. The CentriMag was used as a control pump because of its low blood damage profile. Samples were collected at regular intervals and the following were analyzed: complete cell counts, hemolysis, platelet activation, leukocyte-derived microparticles (LMPs), and von Willebrand factor (vWF) degradation. RESULTS: The HeartMate 2 had the highest levels of hemolysis and platelet activation after 6 hours compared with the HVAD and CentriMag. A decreased granulocyte count, high numbers of LMPs and CD11bBrightHLADR- LMPs, and decreased vWF collagen binding activity was most evident in the HVAD. CONCLUSIONS: The results indicate that it is possible to observe differences between different pump designs during in vitro testing that might translate to clinical performance. This study demonstrates the importance of developing standard in vitro total blood damage methods against which device developers could use to modify design to reduce complication risk long before implantation.

Adopting a flipped classroom approach for teaching molar calculations to biochemistry and genetics students.

The flipped classroom is a relatively new active learning pedagogical intervention, gaining popularity as a blended learning methodology. The flipped classroom comprises two distinct parts, directed learning carried out at the student's own pace away from the classroom and an interactive, class-based activity encouraging problem-solving and experiential learning. This research presents a 1-year study to measure student performance and perception toward a flipped classroom approach to teaching core biochemical calculations to first-year undergraduate biochemistry and genetics students. A post-task questionnaire showed an overall positive student perception with an associated significant improvement in the end of module summative assessment. These results suggest that this teaching approach offers some advantages over more traditional teaching pedagogies.

Utilisation of the STEAP protein family in a diagnostic setting may provide a more comprehensive prognosis of prostate cancer.

Prostate cancer is the second most common cancer diagnosed in men worldwide; however, few patients are affected by clinically significant disease within their lifetime. Unfortunately, the means to discriminate between patients with indolent disease and those who progress to aggressive prostate cancer is currently unavailable, resulting in over-treatment of patients. We therefore aimed to determine biomarkers of prostate cancer that can be used in the clinic to aid the diagnosis and prognosis. Immunohistochemistry analysis was carried out on prostate cancer specimens with a range of Gleason scores. Samples were stained and analysed for intensity of the Seven Transmembrane Epithelial Antigen of the Prostate (STEAP)-1, -2, -3, -4 and the Divalent Metal Transporter 1 (DMT1) proteins to determine suitable biomarkers for classification of patients likely to develop aggressive prostate cancer. Additionally, these proteins were also analysed to determine whether any would be able to predict future relapse using Kaplan Meier analysis. Data generated demonstrated that the protein expression levels of STEAP2 correlated significantly with Gleason score; furthermore, STEAP4 was a significant predictor of relapse. This data indicates that STEAP2 could be potential prognostic candidate for use in combination with the current prostate cancer detection methods and the presence of STEAP4 could be an indicator of possible relapse.

Developing a blood-based gene mutation assay as a novel biomarker for oesophageal adenocarcinoma.

The Phosphatidylinositol glycan class A (PIG-A) gene mutation assay phenotypically measures erythrocyte mutations, assessed here for their correlation to neoplastic progression in the gastro-oesophageal reflux disease (GORD)-Barrett's metaplasia (BM)-oesophageal adenocarcinoma (OAC) model. Endoscopy patients underwent venipuncture and erythrocytes fluorescently stained for glycosyl phosphatidylinositol (GPI)-anchored proteins; CD55 and CD59. Using flow cytometry, GPI-anchor negative erythrocytes (mutants) were scored and compared amongst groups. The study enlisted 200 patients and 137 healthy volunteers. OAC patients had a three-fold increase in erythrocyte mutant frequency (EMF) compared to GORD patients (p < 0.001) and healthy volunteers (p < 0.001). In OAC patients, higher EMF was associated with worsening tumour staging (p = 0.014), nodal involvement (p = 0.019) and metastatic disease (p = 0.008). Chemotherapy patients demonstrated EMF's over 19-times higher than GORD patients. Patients were further classified into groups containing those with non-neoplastic disease and those with high-grade dysplasia/cancer with 72.1% of cases correctly classified by high EMF. Within the non-neoplastic group, aspirin users had lower EMF (p = 0.001) and there was a positive correlation between body mass index (p = 0.03) and age (p < 0.001) and EMF. Smokers had EMF's over double that of non-smokers (p = 0.011). Results suggest this test could help detect OAC and may be a useful predictor of disease progression.

The effects of a new Tendo-Achilles Pathway (TAP) on an orthopaedic department- A quality improvement study.

BACKGROUND: Achilles tendinopathy is a common pathology that is considered difficult to treat. At a time of austerity in the NHS it is essential to have carefully designed pathways that are monitored in terms of cost and effectiveness. However, a paucity of evidence exists for what the "best value" dedicated "joined up" pathway of care is for this difficult condition. OBJECTIVES: Design, implement and evaluate the impact of a new therapist lead pathway for Tendon- Achilles Pain (TAP).  METHODS: Process mapping, driver diagrams, stakeholder analysis and a series of Plan-Do-Study-Act cycles were used to design and implement TAP. To assess the impact of TAP, data was compared on whole system measures for 46 patients treated with referral to the traditional service (without TAP) and 46 patients managed according to the newly designed pathway (with TAP). A cost analysis was also conducted. RESULTS: A quality improvement approach led to the successful design and implementation of a therapist lead TAP. The impact of TAP included positive effects on patient satisfaction, a decrease in duplication of treatments, investigations and inappropriate reviews with consultants. No safety concerns were found. TAP was also £44,000 cheaper per annum than the previous service. CONCLUSION: Collaboration between orthopaedic and therapy services has resulted in a standardised pathway of care for patients with an Achilles tendinopathy.  It has removed unwanted variation, provided an opportunity to monitor the outcomes of treatments and resulted in decreased cost for the health board.