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.

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.

Gardner's Syndrome revisited: a clinical case and overview of the literature.

Gardner's syndrome (GS), a variant of familial adenomatous polyposis (FAP), remains a life-threatening condition of significant dental relevance. Clinicians can play an important role in the identification of this condition as the dental manifestations often precede the development of intestinal polyposis. This article describes a clinical case in which identification of the dental features of GS during routine orthodontic assessment resulted in the early diagnosis of this condition, which was previously unrecognised in a young female patient.

Ponatinib as targeted therapy for FGFR1 fusions associated with the 8p11 myeloproliferative syndrome.

The 8p11 myeloproliferative syndrome is a rare, aggressive myeloproliferative neoplasm characterized by constitutively active FGFR1 fusion proteins that arise from specific chromosomal translocations and which drive aberrant proliferation. Although FGFR1 inhibitors have shown in vitro activity against FGFR1 fusions, none are in use clinically and there is a need to assess additional compounds as potential therapy. Here we use cell lines and primary cells to investigate ponatinib (AP24534). Ponatinib-treated Ba/F3 cells transformed by ZMYM2-FGFR1 and BCR-FGFR1 and the FGFR1OP2-FGFR1 positive KG1A cell line showed reduced proliferation and decreased survival when compared to control cells. Inhibition induced apoptosis and reduced phosphorylation of the FGFR1 fusion proteins and substrates. Ponatinib-treated cells from 8p11 myeloproliferative syndrome patients (n=5) showed reduced colony growth compared to controls. In one evaluable patient, ponatinib specifically reduced numbers of FGFR1-fusion gene positive colonies. Ponatinib, therefore, shows considerable promise for the treatment of patients with 8p11 myeloproliferative syndrome.

Ruxolitinib as potential targeted therapy for patients with JAK2 rearrangements.

JAK2 fusion genes are rare but recurrent abnormalities associated with diverse, clinically heterogeneous hematologic malignancies. Here we assess the JAK1/2 inhibitor ruxolitinib as therapy for patients with JAK2-rearrangement associated myeloproliferative neoplasms (MPN). Ruxolitinib-treated Ba/F3 cells transformed to IL3 independence by ETV6-JAK2 showed reduced proliferation and survival (IC(50) = 370 nM) compared with KG1A or Ba/F3 cells transformed by BCR-ABL1, SPBN1-FLT3 and ZMYM2-FGFR1 (IC(50) > 10 µM for all). Inhibition was associated with reduced phosphorylation of ETV6-JAK2, ERK, STAT5 and AKT. Primary cell growth from 2 patients with JAK2 rearrangement and one patient with JAK2 amplification was assessed in methylcellulose assays. Reduced colony growth was seen for all patients in ruxolitinib-treated cultures compared with healthy controls (n=7). Fluorescence in situ hybridization showed reduced growth of JAK2-rearrangement positive colonies compared to JAK2-rearrangement negative colonies. Our data, therefore, provide evidence that ruxolitinib is a promising therapy for treatment of patients with JAK2 fusion genes.

Improving documentation of visual acuity in patients suffering facial fractures.

Failure to identify eye injuries associated with facial fractures can lead to life-altering morbidity. Oral and maxillofacial surgery teams receiving referrals of patients with these injuries have a vital role in ensuring that visual acuity (VA) is recorded at the time of presentation. We present a clinical audit of documentation of VA in 126 patients who sustained orbital floor and zygoma fractures. Our intervention involved a focussed teaching session for trainees responsible for taking such referrals. VA was appropriately documented in 16.5% before the session and 57.1% afterwards. This study shows that education of junior trainees gives rise to an increase in the proportion of patients where VA is properly documented. We suggest this teaching should occur routinely at junior doctor departmental inductions.

Anterior resection syndrome.

Up to 80% of patients with rectal cancer undergo sphincter-preserving surgery. It is widely accepted that up to 90% of such patients will subsequently have a change in bowel habit, ranging from increased bowel frequency to faecal incontinence or evacuatory dysfunction. This wide spectrum of symptoms after resection and reconstruction of the rectum has been termed anterior resection syndrome. Currently, no precise definition or causal mechanisms have been established. This disordered bowel function has a substantial negative effect on quality of life. Previous reviews have mainly focused on different colonic reconstructive configurations and their comparative effects on daily function and quality of life. The present Review explores the potential mechanisms underlying disturbed functions, as well as current, novel, and future treatment options.

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.

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.

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.

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.

Labeling and family resemblance in the discrimination of polymorphous categories by pigeons.

Two experiments examined whether pigeons discriminate polymorphous categories on the basis of a single highly predictive feature or overall similarity. In the first experiment, pigeons were trained to discriminate between categories of photographs of complex real objects. Within these pictures, single features had been manipulated to produce a highly salient texture cue. Either the picture or the texture provided a reliable cue for discrimination during training, but in probe tests, the picture and texture cues were put into conflict. Some pigeons showed a significant tendency to discriminate on the basis of the picture cue (overall similarity or family resemblance), whereas others appeared to rely on the manipulated texture cue. The second experiment used artificial polymorphous categories in which one dimension of the stimulus provided a completely reliable cue to category membership, whereas three other dimensions provided cues that were individually unreliable but collectively provided a completely reliable basis for discrimination. Most pigeons came under the control of the reliable cue rather than the unreliable cues. A minority, however, came under the control of single dimensions from the unreliable set. We conclude that cue salience can be more important than cue reliability in determining what features will control behavior when multiple cues are available.

Sickle cell disease, dentistry and conscious sedation.

UNLABELLED: The features of sickle cell disease (SCD) are described. Two case reports of patients treated in a Dental Institute are presented and the dental management of patients with SCD discussed. Since infection is one of the major risk factors for sickle cell crisis, the prevention of oral disease and infection is vital for this group of patients and there is no contra-indication to the delivery of dental treatment under local anaesthetic with inhalational sedation if required in the primary care setting. Since patients with sickle cell disease are particularly vulnerable to the effects of periods of hypoxia, which may produce significant morbidity, and because of the additional practical challenges in sedating this group of patients, intravenous sedation should be undertaken in a specialist unit. CLINICAL RELEVANCE: The increasing prevalence of sickle cell disease highlights the importance of dentists practising in multi-cultural communities having an understanding of this condition and its implications on their clinical practice. This will facilitate the safe management of patients with sickle cell disease.

Delirium: prevention, clinical features and management.

Delirium is a common condition among hospital inpatients and people in long-term care settings. It is an acute confusional state associated with poor outcomes. Delirium is poorly recognised and managed despite evidence to suggest it is preventable in up to one third of cases. In July 2010, the National Institute for Health and Clinical Excellence published a comprehensive clinical practice guideline on the diagnosis, prevention and management of delirium. This article discusses the clinical features of delirium in relation to the guideline. It recommends that all clinical staff Scaring for older people should take on the responsibility to 'think delirium' and improve the quality of care for these patients.

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.

Band slippage and erosion after laparoscopic gastric banding: a meta-analysis.

BACKGROUND: Laparoscopic adjustable gastric banding has the lowest morbidity and mortality rates among the common bariatric procedures. Troublesome complications associated with this procedure include band slippage and erosion, often requiring revisionary surgery. Rates of slippage have decreased, and this appears to be due to changes in surgical technique. In the authors' experience, units with a low slippage rate also have a low erosion rate and vice versa. Thus a systematic review was undertaken to investigate this relationship. METHODS: Electronic databases were searched up to 31 December 2008. Publications focusing solely on laparoscopic adjustable gastric banding with at least 500 patients and a minimum follow-up period of 2 years were included in the study. Publications in languages other than English and those that failed to mention erosion and slippage rates were excluded. Multivariate meta-analyses were conducted separately for the pars flaccida group, the perigastric group, and the combined overall group to pool the average rates of both erosion and slippage for each paper included. The correlation between the occurrence rates for both erosion and slippage then was examined. RESULTS: The inclusion criteria were met by 19 studies. The mean rates of erosion and slippage were 1.03 and 4.93, respectively. The results demonstrated a statistically significant overall correlation between erosion and slippage rates (r = 0.48, p = 0.032). A very strong correlation between erosion and slippage was found if the perigastric technique of insertion was used (r = 0.99, p < 0.001). However, this correlation was not statistically significant where the pars flaccida technique of insertion was used (r = 0.34, p = 0.38). CONCLUSIONS: The high correlation rate between erosion and slippage for the perigastric group strongly suggests that these complications share a common pathophysiology. This correlation is reduced with the pars flaccida technique, suggesting that perhaps a different etiology is associated with erosion in these studies. Surgical techniques that help to eliminate lap band slippage should also reduce rates of erosion.

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.

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.

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.