HIDDEN2: Study protocol for the hospital deep vein thrombosis detection study in patients with cancer receiving palliative care.

INTRODUCTION: Medical patients, admitted acutely to hospital, are at risk of venous thromboembolism (VTE). Clinical guidelines advise thromboprophylaxis prophylaxis for those at high risk of VTE. VTE is a common sequela of cancer, but guidelines take little consideration of cancer as an independent risk factor and their utility in palliative care patients is unclear. The hospice inpatient deep vein thrombosis (DVT) detection study (HIDDen) reported a 28% prevalence of asymptomatic iliofemoral DVT in hospice patients of poor performance status (PS) and prognosis, calling into question the utility of thromboprophylaxis in the palliative care setting. However, the majority of cancer inpatients receiving palliative care are admitted to hospital through the acute medical setting, yet their risk factors for VTE may differ from those admitted to hospices. OBJECTIVE: To better understand the prevalence and behaviours of VTE in patients with cancer receiving palliative care who are admitted as an acute medical emergency. DESIGN: Multicentre, observational cohort study. SETTING: Secondary care acute hospitals in South Wales, UK. PATIENTS: We plan to recruit 232 patients≥18 years old with a diagnosis of incurable cancer, and/or receiving palliative or best supportive care who are admitted acutely to hospital. Patients will be followed up for a maximum of 6 months following registration. PRIMARY OUTCOME: Presence of lower extremity DVT. SECONDARY OUTCOMES: Symptom burden attributed to DVT or pulmonary embolism, patient PS, patient demographics and development of new VTE within 90 days of registration. ANALYSIS: The study statistical analysis plan will document analysis, methodology and procedures. ETHICS AND DISSEMINATION: Ethical approval was obtained from the Wales Research Ethics Committee, reference 22/WA/0037 (IRAS 306352)-the main trial results will be analysed as soon as practically possible and the publication shared with investigators and on sponsor website; applications to access trial data will be subject to sponsor review process.

Quantifying blue carbon stocks and the role of protected areas to conserve coastal wetlands.

Vegetated coastal ecosystems, in particular mangroves, tidal marshes and seagrasses are highly efficient at sequestering and storing carbon, making them valuable assets for climate change mitigation and adaptation. The state of Queensland, in northeastern Australia, contains almost half of the total area of these blue carbon ecosystems in the country, yet there are few detailed regional or state-wide assessments of their total sedimentary organic carbon (SOC) stocks. We compiled existing SOC data and used boosted regression tree models to evaluate the influence of environmental variables in explaining the variability in SOC stocks, and to produce spatially explicit blue carbon estimates. The final models explained 75 % (for mangroves and tidal marshes) and 65 % (for seagrasses) of the variability in SOC stocks. Total SOC stocks in the state of Queensland were estimated at 569 ± 98 Tg C (173 ± 32 Tg C, 232 ± 50 Tg C, and 164 ± 16 Tg C from mangroves, tidal marshes and seagrasses, respectively). Regional predictions for each of Queensland's eleven Natural Resource Management regions revealed that 60 % of the state's SOC stocks occurred within three regions (Cape York, Torres Strait and Southern Gulf Natural Resource Management regions) due to a combination of high values of SOC stocks and large areas of coastal wetlands. Protected areas in Queensland play an important role in conserving SOC assets in Queensland's coastal wetlands. For example, ~19 Tg C within terrestrial protected areas, ~27 Tg C within marine protected areas and ~ 40 Tg C within areas of matters of State Environmental Significance. Using multi-decadal (1987-2020) mapped distributions of mangroves in Queensland; we found that mangrove area increased by approximately 30,000 ha from 1987 to 2020, which led to temporal fluctuations in mangrove plant and SOC stocks. We estimated that plant stocks decreased from ~45 Tg C in 1987 to ~34.2 Tg C in 2020, while SOC stocks remained relatively constant from ~107.9 Tg C in 1987 to 108.0 Tg C in 2020. Considering the level of current protection, emissions from mangrove deforestation are potentially very low; therefore, representing minor opportunities for mangrove blue carbon projects in the region. Our study provides much needed information on current trends in carbon stocks and their conservation in Queensland's coastal wetlands, while also contributing to guide future management actions, including blue carbon restoration projects.

A report card approach to describe temporal and spatial trends in parameters for coastal seagrass habitats.

Report cards that are designed to monitor environmental trends have the potential to provide a powerful communication tool because they are easy to understand and accessible to the general public, scientists, managers and policy makers. Given this functionality, they are increasingly popular in marine ecosystem reporting. We describe a report card method for seagrass that incorporates spatial and temporal variability in three metrics-meadow area, species and biomass-developed using long-term (greater than 10 years) monitoring data. This framework summarises large amounts of spatially and temporally complex data to give a numeric score that provides reliable comparisons of seagrass condition in both persistent and naturally variable meadows. We provide an example of how this is applied to seagrass meadows in an industrial port in the Great Barrier Reef World Heritage Area of north-eastern Australia.

A light-guiding urinary catheter for the inhibition of Proteus mirabilis biofilm formation.

Catheter-associated urinary tract infection (CAUTI) is a leading cause of hospital-acquired infections worldwide causing debilitating illness for patients as well as a significant financial and treatment burden on health services. CAUTI is linked with the build-up of biofilms on catheter surfaces which act as a reservoir for infection. Additionally, urease-producing bacteria such as Gram-negative Proteus mirabilis (PM), can form crystalline biofilms which encrust catheter surfaces ultimately leading to blockages which require immediate removal of the catheter. Currently there are limited treatments available to prevent the formation of biofilms by PM as well as other urinary tract infection causing bacteria. A novel concept for a light-guiding urinary catheter is presented where a silicone elastomer waveguide incorporated along the length of the catheter is used to irradiate the catheter surfaces with antimicrobial blue light (405 nm) to prevent biofilm formation in situ. The prototype device is mass producible while also easy to fabricate in a lab setting for research studies. The inhibitory effect of blue light on PM biofilm formation over a range of irradiances is described for the first time showing an LD90 at 192-345 J/cm2 and total inhibition at 1,700 J/cm2 In vitro studies show that the light-guiding catheter (LGC) prototypes exhibit a 98% inhibition in PM biofilm formation inside the catheter lumen at an average estimated irradiance of 30-50 mW/cm2 (324-540 J/cm2 fluence) showing that the concept is highly effective, promising to be a powerful and economical antimicrobial approach to prevent catheter associated biofilm development and blockage.

Current and future carbon stocks in coastal wetlands within the Great Barrier Reef catchments.

Australia's Great Barrier Reef (GBR) catchments include some of the world's most intact coastal wetlands comprising diverse mangrove, seagrass and tidal marsh ecosystems. Although these ecosystems are highly efficient at storing carbon in marine sediments, their soil organic carbon (SOC) stocks and the potential changes resulting from climate impacts, including sea level rise are not well understood. For the first time, we estimated SOC stocks and their drivers within the range of coastal wetlands of GBR catchments using boosted regression trees (i.e. a machine learning approach and ensemble method for modelling the relationship between response and explanatory variables) and identified the potential changes in future stocks due to sea level rise. We found levels of SOC stocks of mangrove and seagrass meadows have different drivers, with climatic variables such as temperature, rainfall and solar radiation, showing significant contributions in accounting for variation in SOC stocks in mangroves. In contrast, soil type accounted for most of the variability in seagrass meadows. Total SOC stock in the GBR catchments, including mangroves, seagrass meadows and tidal marshes, is approximately 137 Tg C, which represents 9%-13% of Australia's total SOC stock while encompassing only 4%-6% of the total extent of Australian coastal wetlands. In a global context, this could represent 0.5%-1.4% of global SOC stock. Our study suggests that landward migration due to projected sea level rise has the potential to enhance carbon accumulation with total carbon gains between 0.16 and 0.46 Tg C and provides an opportunity for future restoration to enhance blue carbon.

A Springboard for physicians returning to practice.

BACKGROUND: Many physicians take time out of training and have decreased confidence and poor performance ratings on their return. Courses employing multiple educational methods have been shown to be effective in easing learners into new clinical roles during transition periods but, to date, there is limited evidence for courses to support trainees returning to practice (RTP). METHODS: A 2-day course, named Springboard, was developed, specifically to address the needs of trainee physicians RTP. It employed a blended, multi-modal approach to learning, including lectures, workshops, case-based sessions, interactive panel discussions, small group teaching, peer-led practical advice sessions and simulation training. Springboard was delivered eight times between 2014 and 2019 with a total of 540 doctors attending. We analysed participant pre-and post-course questionnaire feedback. RESULTS: Reasons for doctors taking time out of training included parental leave, research, fellowships in education and leadership, health-related absence and career breaks. Time out of training ranged between 3 months and 6 years. A significant pre/post-course increase in candidates' self-reported leadership skills and confidence in being prepared to return to practice was demonstrated alongside an appreciation of a multi-modal, 'boot camp' course delivered by expert faculty and a networking experience. DISCUSSION: Dedicated training courses tailored to the needs of physicians RTP provide an opportunity for improving confidence relating to many areas of clinical and non-clinical practice as well as providing an environment for networking and sharing experiences. Further work would be valuable to establish the potential of providing this on a larger scale.

Evaluation of training programmes mapped to the new internal medicine curriculum.

In preparation for the internal medicine training (IMT) programme introduced in 2019, the core medical training (CMT) programme in London was made 'IMT-ready' in 2018 by creating new rotations that reflected the compulsory requirements of the first 2 years of the IMT curriculum, including provision of the requisite number of critical care placements. Core medical trainees completed posts within the 'IMT-ready' programme between August 2018 and August 2019, during which time the trainee experience was evaluated. A total of 497 responses were received. Of these, 96% of trainees were on an 'acute unselected take' on-call rota, 79% were able to attend outpatient clinics, 80% had the opportunity to practise procedural skills and 88% had the opportunity to apply palliative care skills. Clear areas for improvement were identified that predominantly focused on the need to optimise trainee attendance of outpatient clinics and the number of patients seen during an acute take. With respect to future career intentions, only 63% of trainees planned on applying to a group 1 (with general medicine) higher medical specialty. Thematic analysis of trainees in critical care placements highlighted an appreciation of the level of senior support, feeling well integrated into the team, a positive experience of induction and excellent opportunities for performing procedures.

Training educational supervisors to support physician trainees returning to practice.

Physicians take time out of training for a variety of reasons and, on their return, they often lack confidence and feel 'out of touch'. These trainees require enhanced support and concerns have been raised about trainers' lack of skills and knowledge in this area. A standardised workshop was developed and delivered to address this with a mixed-methods evaluation approach used to analyse data from participants before and after training. Quantitative analysis showed significant pre- to post-course improvements in trainers' ability to understand, explain and manage issues pertaining to trainees taking time out of training. Qualitative analysis yielded three 'learning' themes surrounding knowledge, understanding and awareness of support needed for returning trainees and three 'action' themes surrounding disseminating information, providing resources and actively supporting returning trainees. Framework analysis of follow-up interviews demonstrated not only retention of topics learned but also positive changes in behaviour.

Mutational mechanisms of EZH2 inactivation in myeloid neoplasms.

EZH2, a component of the polycomb repressive complex 2, catalyses the trimethylation of histone H3 lysine 27, a chromatin mark associated with transcriptional repression. EZH2 loss-of-function mutations are seen in myeloid neoplasms and are associated with an adverse prognosis. Missense mutations in the SET/CXC domain abrogate catalytic activity as assessed by in vitro histone methylation assays, but missense mutations clustering in the conserved DI and DII regions retain activity. To understand the role of DI and DII mutations, we initially developed a cell-based histone methylation assay to test activity in a cellular context. Murine induced pluripotent stem cells lacking EZH2 were transiently transfected with wild type or mutant EZH2 (n = 15) and any resulting histone methylation was measured by flow cytometry. All DI mutations (n = 5) resulted in complete or partial loss of methylation activity whilst 5/6 DII mutations retained activity. Next, we assessed the possibility of splicing abnormalities induced by exon 8 mutations (encoding DII) using RT-PCR from primary patient samples and mini-gene assays. Exon 8 mutations resulted in skipping of exon 8 and an out-of-frame transcript. We have therefore shown that mutations within regions encoding EZH2 domains DI and DII are pathogenic by loss of function and exon skipping, respectively.

High variability of Blue Carbon storage in seagrass meadows at the estuary scale.

Seagrass meadows are considered important natural carbon sinks due to their capacity to store organic carbon (Corg) in sediments. However, the spatial heterogeneity of carbon storage in seagrass sediments needs to be better understood to improve accuracy of Blue Carbon assessments, particularly when strong gradients are present. We performed an intensive coring study within a sub-tropical estuary to assess the spatial variability in sedimentary Corg associated with seagrasses, and to identify the key factors promoting this variability. We found a strong spatial pattern within the estuary, from 52.16 mg Corg cm-3 in seagrass meadows in the upper parts, declining to 1.06 mg Corg cm-3 in seagrass meadows at the estuary mouth, despite a general gradient of increasing seagrass cover and seagrass habitat extent in the opposite direction. The sedimentary Corg underneath seagrass meadows came principally from allochthonous (non-seagrass) sources (~70-90 %), while the contribution of seagrasses was low (~10-30 %) throughout the entire estuary. Our results showed that Corg stored in sediments of seagrass meadows can be highly variable within an estuary, attributed largely to accumulation of fine sediments and inputs of allochthonous sources. Local features and the existence of spatial gradients must be considered in Blue Carbon estimates in coastal ecosystems.

Laser-patterned paper-based sensors for rapid point-of-care detection and antibiotic-resistance testing of bacterial infections.

Antimicrobial resistance (AMR) has been identified by the World Health Organisation as a global threat that currently claims at least 25,000 deaths each year in Europe and 700,000 globally; the number is projected to reach 10 million per year between 2015 and 2050. Therefore, there is an urgent need for low-cost but reliable point-of-care diagnostics for early screening of infections especially in developing countries lacking in basic infrastructure and trained personnel. This work is aimed at developing such a device, a paper-based microfluidic device for infection testing by an unskilled user in a low resource setting. Here, we present our work relating to the use of our laser-patterned paper-based devices for detection and susceptibility testing of Escherichia coli, via a simple visually observable colour change. The results indicate the suitability of our integrated paper devices for timely identification of bacterial infections at the point-of-care and their usefulness in providing a hugely beneficial pathway for accurate antibiotic prescribing and thus a novel route to tackling the global challenge of AMR.

One Anastomosis Gastric Bypass in Morbidly Obese Patients with BMI ≥ 50 kg/m2: a Systematic Review Comparing It with Roux-En-Y Gastric Bypass and Sleeve Gastrectomy.

BACKGROUND: To explore the role of one anastomosis (Mini) gastric bypass (OAGB) for the super-obese patients. METHOD: Literature review was performed in March 2019 as per PRISMA guidelines. RESULTS: A total of 318 patients were identified. Mean age was 31.8 years. Mean body mass index (BMI) was 57.4 kg/m2. The mean operative time was 93.1 min with median length of stay of 4.5 days. The biliopancreatic limb (BPL) varied from 190 to 350 cm(median 280 cm). Early mortality was 0.31% with seven complications (including 1 revisional surgery). Leak rate was 0%. Mean %excess weight loss (EWL) at 12, 18-24 and 60 months was 67.7%, 71.6% and 90.75%, respectively. CONCLUSIONS: OAGB is a safe and effective option for management of super and super-super obese patients with tailoring of the BPL. Larger comparison, follow-up and randomised trials are necessary to validate these findings.

PRR14L mutations are associated with chromosome 22 acquired uniparental disomy, age-related clonal hematopoiesis and myeloid neoplasia.

Acquired uniparental disomy (aUPD, also known as copy-neutral loss of heterozygosity) is a common feature of cancer cells and characterized by extended tracts of somatically-acquired homozygosity without any concurrent loss or gain of genetic material. The presumed genetic targets of many regions of aUPD remain unknown. Here we describe the association of chromosome 22 aUPD with mutations that delete the C-terminus of PRR14L in patients with chronic myelomonocytic leukemia (CMML), related myeloid neoplasms and age-related clonal hematopoiesis (ARCH). Myeloid panel analysis identified a median of three additional mutated genes (range 1-6) in cases with a myeloid neoplasm (n = 8), but no additional mutations in cases with ARCH (n = 2) suggesting that mutated PRR14L alone may be sufficient to drive clonality. PRR14L has very limited homology to other proteins and its function is unknown. ShRNA knockdown of PRR14L in human CD34+ cells followed by in vitro growth and differentiation assays showed an increase in monocytes and decrease in neutrophils, consistent with a CMML-like phenotype. RNA-Seq and cellular localization studies suggest a role for PRR14L in cell division. PRR14L is thus a novel, biallelically mutated gene and potential founding abnormality in myeloid neoplasms.

Low pyrrolizidine alkaloid levels in perennial ryegrass is associated with the absence of a homospermidine synthase gene.

BACKGROUND: Pyrrolizidine alkaloids (PAs) are a class of secondary metabolites that function as feeding deterrents in a range of different plant species. In perennial ryegrass (Lolium perenne L.) the only PAs that have been identified are the thesinine-rhamnoside group, which displays significant genetic variation. Homospermidine synthase (HSS) has evolved from deoxyhypusine synthase (DHS) and catalyses the first step in the PA pathway, making it a key candidate for the investigation of genes influencing observed PA trait variation. RESULTS: During PCR amplification and sequence analysis of DHS we identified two putative HSS genes in perennial ryegrass. One of the genes (LpHSS1) was absent in some perennial ryegrass plants. Thesinine-rhamnoside levels were measured using liquid chromatography coupled with mass spectrometry in a diverse association mapping population, consisting of 693 plants free of fungal endophytic symbionts. Association tests that accounted for population structure identified a significant association of absence of the LpHSS1 gene with lower levels of thesinine-rhamnoside PAs. HSS-like gene sequences were identified for other grass species of the Poaceae, including tall fescue, wheat, maize and sorghum. CONCLUSION: HSS is situated at the crucial first step in the PA pathway making it an important candidate gene for investigation of involvement in PA phenotypic variation. In this study, PA level in perennial ryegrass was strongly associated with the presence or absence of the LpHSS1 gene. A genetic marker, developed for the presence/absence of LpHSS1, may be used for marker-assisted breeding to either lower or increase PAs in breeding populations of perennial or Italian ryegrass to investigate a potential role in the deterrence of herbivore pests. The presence of HSS-like genes in several other Poaceae species suggests that PA biosynthesis may occur in plant family members beyond perennial ryegrass and tall fescue and identifies a potential route for manipulating PA levels.

The Multiple Consultant Report: new assessment; same old problems.

BACKGROUND: In December 2013 the Multiple Consultant Report (MCR) was introduced as an assessment tool for junior doctors (i.e. doctors below specialist status) in the UK, including those undertaking core medical training (CMT). It aims to capture the views of consultant supervisors about a doctor's clinical performance. OBJECTIVE: Despite the mandatory nature of the MCR there is no published academic evaluation of this tool as an assessment of, or for, learning. The aim of this study was to explore opinions on the MCR amongst core medical trainees at a large London teaching hospital. STUDY DESIGN: Questionnaires were distributed to the entire cohort of 42 core medical trainees. Data were enriched by a focus group. Inductive thematic analysis was used to analyse the data qualitatively. FINDINGS: Twenty-two trainees (52%) completed the questionnaire. Six trainees attended a single focus group. A key issue highlighted by this study was a lack of awareness amongst trainees (and assessors) surrounding the introduction and purpose of the MCR. Ineffective feedback limited the potential impact of the assessment, but many trainees reported a perception that the MCR duplicated existing assessments. Registrars (doctors undergoing a minimum 4 years of specialty training along with higher training in general medicine) were considered better placed to offer detailed feedback regarding the clinical performance of core medical trainees, within the context of the MCR. [The MRC] aims to capture the views of consultant supervisors about a doctor's clinical performance CONCLUSIONS: The MCR has many of the weaknesses and strengths observed with existing assessments. Given this, perhaps it is time to reconsider our approach to workplace-based assessments.

Intestinal spirochaetosis mimicking acute appendicitis with review of the literature.

Human intestinal spirochaetosis is a well-established micro-organism existing in the colon. It is less commonly seen in the appendix, and rarely presents as acute appendicitis. We present a case of a man presenting with symptoms consistent with acute appendicitis. The literature on spirochaetosis presenting as acute appendicitis is also reviewed.

Trials and tribulations of the annual review of competence progression - lessons learned from core medical training in London.

The annual review of competence progression (ARCP) was introduced as a way of keeping records and reviewing satisfactory progress through a medical curriculum for doctors in training. It provides public assurance that doctors are trained to a satisfactory standard and are fit for purpose. A routine external review of the core medical training (CMT) ARCPs in London revealed documentation of satisfactory progression of trainees to the next level of training without the evidence to support their completion of the curriculum. An internal review and series of process interventions were subsequently conducted and implemented to improve the quality and standardisation of the ARCPs. This paper reviews these interventions, discusses the lessons learned from the internal review and highlights issues applicable to any ARCP process.

Where did the acute medical trainees go? A review of the career pathways of acute care common stem acute medical trainees in London.

Acute care common stem acute medicine (ACCS AM) training was designed to develop competent multi-skilled acute physicians to manage patients with multimorbidity from 'door to discharge' in an era of increasing acute hospital admissions. Recent surveys by the Royal College of Physicians have suggested that acute medical specialties are proving less attractive to trainees. However, data on the career pathways taken by trainees completing core acute medical training has been lacking. Using London as a region with a 100% fill rate for its ACCS AM training programme, this study showed only 14% of trainees go on to higher specialty training in acute internal medicine and a further 10% to pursue higher medical specialty training with dual accreditation with internal medicine. 16% of trainees switched from ACCS AM to emergency medicine or anaesthetics during core ACCS training, and intensive care medicine proved to be the most popular career choice for ACCS AM trainees (21%). The ACCS AM training programme therefore does not appear to be providing what it was set out to do and this paper discusses the potential causes and effects.