Fluvial sediment supply to a mega-delta reduced by shifting tropical-cyclone activity.

The world's rivers deliver 19 billion tonnes of sediment to the coastal zone annually, with a considerable fraction being sequestered in large deltas, home to over 500 million people. Most (more than 70 per cent) large deltas are under threat from a combination of rising sea levels, ground surface subsidence and anthropogenic sediment trapping, and a sustainable supply of fluvial sediment is therefore critical to prevent deltas being 'drowned' by rising relative sea levels. Here we combine suspended sediment load data from the Mekong River with hydrological model simulations to isolate the role of tropical cyclones in transmitting suspended sediment to one of the world's great deltas. We demonstrate that spatial variations in the Mekong's suspended sediment load are correlated (r = 0.765, P < 0.1) with observed variations in tropical-cyclone climatology, and that a substantial portion (32 per cent) of the suspended sediment load reaching the delta is delivered by runoff generated by rainfall associated with tropical cyclones. Furthermore, we estimate that the suspended load to the delta has declined by 52.6 ± 10.2 megatonnes over recent years (1981-2005), of which 33.0 ± 7.1 megatonnes is due to a shift in tropical-cyclone climatology. Consequently, tropical cyclones have a key role in controlling the magnitude of, and variability in, transmission of suspended sediment to the coast. It is likely that anthropogenic sediment trapping in upstream reservoirs is a dominant factor in explaining past, and anticipating future, declines in suspended sediment loads reaching the world's major deltas. However, our study shows that changes in tropical-cyclone climatology affect trends in fluvial suspended sediment loads and thus are also key to fully assessing the risk posed to vulnerable coastal systems.

Postimplantation syndrome in endovascular aortic aneurysm repair - a systematic review.

Postimplantation syndrome (PIS) following endovascular aortic aneurysm repair (EVAR) is a poorly understood phenomenon occurring in the early post-operative course. The underlying aetiology, risk factors, clinical sequalae, and treatment options, are largely unknown. The lack of any standardised diagnostic criteria limits current research in this field. The MEDLINE database was interrogated using a Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) search strategy. Five search terms were used; "postimplantation syndrome" AND "aneurysm", AND "infection", AND "complications", AND "biomarkers", AND "outcomes". 19 studies were included in the review process, reporting a 17.4%-39.0% incidence of PIS. IL-6 was the most commonly elevated biomarker in PIS vs. non-PIS patients. There was a higher incidence of PIS in patients who received polyester rather than expanded-polytetrafluoroethylene (ePTFE) grafts. There was a lower rate of type 2 endoleaks observed in patients who developed PIS. Early major adverse cardiovascular events (MACE) were higher in PIS patients, however there were no studies reporting long-term MACE. Length of stay was higher in PIS patients. Current data support the role of IL-6 as being key to the development of PIS following EVAR. Further work describing the effect that PIS has on long-term clinical outcomes is needed. Lack of standardised diagnostic criteria limit the reporting of PIS between centres, the criteria proposed by this review may resolve this.

Wound management: Investigating the interprofessional decision-making process.

Our aim is to develop a robust socio-geographical transferable theory outlining the basic social process used by members of an interprofessional health care team when making decisions around wound care management. Using a qualitative multigrounded theory approach, three focus groups were held at the Royal Victoria Regional Health Centre in Barrie, Ontario, Canada, comprised of 13 clinicians who participate in wound care decision-making. Data were analysed using an approach developed for multigrounded theory. A Critical Realist theoretical lens was applied to data analysis in the development of conclusions. Ten categories were identified before thematic saturation. Category interactions developed a perceived basic social process outlining how interprofessional clinicians determine how they approach wound care decisions: patient factors, scope of practice, equipment and supplies, internal clinician factors, knowledge and education, interprofessional team, assessment, wound care specialist consultation, and care plan, as well as documentation and communication. Understanding how wound care decision-making is determined by interprofessional health care providers will assist clinical leaders and policy makers in creating a foundation for determining resource allocation, allowing clinicians to use evidence-based practice to improve patient and clinician satisfaction, wound healing time, decrease costs, and prevent wound recurrence.

Thermal Imaging Metrology with a Smartphone Sensor.

Thermal imaging cameras are expensive, particularly those designed for measuring high temperature objects with low measurement uncertainty. A wide range of research and industrial applications would benefit from lower cost temperature imaging sensors with improved metrology. To address this problem, we present the first ever quantification methodology for the temperature measurement performance of an ultra-low cost thermal imaging system based on a smartphone sensor. The camera was formed from a back illuminated silicon Complementary Metal Oxide Semiconductor (CMOS) sensor, developed for the smartphone camera market. It was packaged for use with a Raspberry Pi computer. We designed and fitted a custom-made triplet lens assembly. The system performance was characterised with a range of state-of-the-art techniques and metrics: establishing a temperature resolution of below 10 °C in the range 600⁻1000 °C. Furthermore, the scene dependent aspects of combined uncertainty were considered. The minimum angular subtense for which an accurate thermal measurement could be made was determined to be 1.35°, which corresponds to a 23 mm bar at a distance of 1 m, or 45:1 field-of-view in radiation thermometer nomenclature.

Community football teams for people with intellectual disabilities in secure settings: "They take you off the ward, it was like a nice day, and then you get like medals at the end".

BACKGROUND: People with learning disabilities (LD) are particularly vulnerable to mental health and behavioural difficulties, and it has been shown that regular exercise can improve psychosocial well-being as well as physical fitness. This research aims to explore the experiences of men with LD detained in secure settings who have engaged in community football training programmes and identify the benefits of such provision. METHOD: Interviews were conducted with eight patients in a forensic LD service, discussing their experiences of participating in community football. Template analysis was undertaken on the transcripts. RESULTS: Two master themes were identified: physical fitness and psychosocial benefits. As the analysis progressed, new emerging themes were identified around role identity and achievement, as well as extending and refining some of the themes from the original template including fun and belonging. Some anticipated themes were removed from the template entirely. CONCLUSION: The psychosocial benefits of organised community sports programmes far outweigh the physical health benefits. Careful consideration must be given to where on a treatment and rehabilitation pathway non-traditional therapeutic interventions such as sports programmes are offered as an adjunct to specific risk reduction interventions for people with LD in secure settings.

Prescriber Phenotypes: Variability in Topical Rosacea Treatment Patterns Among United States Dermatologists.

Background/Objectives: Aggregate prescribing behavior for inflammatory lesions of rosacea has been described, but individual physician behavior has not been characterized. This study aims to assess the modern state of topical rosacea drug selection by analyzing prescribing patterns among individual dermatologists. Methods: We assessed utilization patterns of four topical papulopustular rosacea agents in 2021 Medicare Part-D data. K-means cluster analysis identified prescriber phenotypes based on the proportion of claims for each drug by physician. Results: Cluster analysis identified four prescriber phenotypes for topical rosacea agents, with the majority favoring metronidazole. In each of the other clusters, metronidazole was co-prescribed alongside the primary agent. Significant predictors of phenotype included patient ages, patient risk scores, and a group practice setting. Conclusions: The study reveals nonuniform prescribing patterns for topical papulopustular rosacea treatments among U.S. dermatologists. While aggregate data indicate diverse drug utilization, cluster analysis suggests that individual prescribers tend to use a limited selection of agents.

Race and ethnicity are inadequate predictors of ambulatory visit length and utilization of preventive services.

Health disparities can be experienced by any disadvantaged group who has limited access to healthcare or decreased quality of care. Quality of care can be measured by physician-patient communication measures such as length of visit, health outcomes, patient satisfaction, or by the services one receives such as screening or health education. This study aims to determine the relationship between length of physician-patient encounter, number of preventive services, ethnicity, and race. This study utilizes data from the National Ambulatory Medical Care Survey (NAMCS) from 2007 to 2016. Visits with a single diagnosis were selected. Visits with the five most frequent diagnoses were selected by International Classification of Diseases, Ninth or Tenth Revision (ICD-9/ICD-10) classification. The primary outcome is time spent with a physician in minutes and the number of preventive services provided represented by the Preventive Service Index (PSI). Of 255,916 visits, non-white individuals made up 16.2% (95% Confidence Interval 15.9-16.4) while Latinos represented 13.4% (95%CI 13.2-13.6) of individuals. Multivariate analysis revealed minimal differences in visit length in race and ethnic groups regardless of diagnosis. Greater PSI was associated with individuals less than 43 years old (Odds Ratio (OR) 2.0, 95% CI 1.8-2.3, p =< 0.0001), those who reside in metropolitan statistical areas (MSAs) (OR 1.2, 95% CI 1.1-1.4, p = 0.006), non-white individuals (OR 1.2, 95% CI 1.1-1.3, p = 0.004), and those with private insurance (OR 1.3, 95% CI 1.1-1.4, p =< 0.0001). Race and ethnicity do not predict length of time with a physician regardless of diagnosis. Age, race, location within a metropolitan area, and insurance are significant but minimal predictors of receiving preventive services in the rank-order leading five most frequent diagnoses. This large, population-based study highlights improvements in the distribution of healthcare services from previous studies.

Extrapulmonary, Chronic Septic Arthritis From Mycobacterium tuberculosis in the Ankle and Subtalar Joints.

In the United States, rates of Mycobacterium tuberculosis infection have been declining for decades. Osteoarticular tuberculosis of the ankle is rarely observed. We present the case of a 65-year-old man who immigrated to the United States from India 24 years before the onset of symptoms. The patient initially reported atraumatic swelling and pain of the left ankle and foot and was treated for venous insufficiency. Later, the patient was referred to a nonsurgical orthopaedic clinic for additional workup and was found to have elevated inflammatory markers. MRI showed septic arthritis and osteomyelitis of the talus, distal tibia, and calcaneus. Joint aspiration revealed elevated white blood cell counts with predominately PMNs. The patient was then referred to an orthopaedic foot and ankle surgeon and underwent extensive irrigation and débridement. The patient was discharged on empiric antibiotics. Culture results from the original joint aspirate returned 14 days after surgery as positive for acid-fast bacillus, later identified as M tuberculosis by sequencing. Empiric antibiotics were discontinued, and the patient was started on appropriate antituberculotic therapy. This case report illustrates the challenge in the diagnosis of skeletal tuberculosis and the importance of including this condition on the differential for patients with atypical foot and ankle presentations.

Discontinuation of government subsidized HIV pre-exposure prophylaxis in Australia: a whole-of-population analysis of dispensing records.

INTRODUCTION: HIV pre-exposure prophylaxis (PrEP) has been government subsidized in Australia since April 2018 and while uptake is high among men who have sex with men, rates of discontinuation are also high. The aims of this study were to examine the impact of discontinuation on overall PrEP usage, the proportion of PrEP users who discontinue and the predictors of discontinuation. METHODS: We used linked de-identified dispensing records of all government subsidized PrEP in Australia between April 2018 and September 2021: a whole-of-population data set. Defining discontinuation as 180 days or more without PrEP after the final dispensed supply, we calculated the number of people who discontinued at each 6-month interval during the study period, the proportion who had discontinued 2 years after the first supply and, using Cox regression, predictors of discontinuation. RESULTS: Of 49,164 people dispensed PrEP (98.5% male, median age 34 years), 40.3% (19,815) had discontinued by September 2021. Within 2 years of their first supply, 11,150 (37.7%) of 29,549 PrEP users had discontinued, including 10.0% after a single dispensed supply. Large variations were observed, particularly according to prescriber characteristics: discontinuation was higher among people prescribed PrEP by low caseload (≤10 patients) prescribers (61.2%) than by high caseload (>100 patients) prescribers (31.1%, p<0.001), and by prescribers practising in areas with low estimated prevalence (<1.0%) of gay men (64.1%) than high (>5%) prevalence (36.7%, p<0.001). Women and younger people were more likely to discontinue, while patients receiving a higher level of government subsidy were less likely. The independent predictors of discontinuation with the greatest effect size were female sex (adjusted hazards ratio [aHR] 2.99, p<0.001), low estimated gay prevalence of prescriber location (aHR 1.98, p<0.001) and low prescriber PrEP caseload (aHR 1.79, p<0.001). CONCLUSIONS: There are high rates of PrEP discontinuation in Australia and some populations are at increased risk of discontinuation. Strategies are needed to support persistence on PrEP and the re-starting of PrEP during periods of risk.

A high-resolution daily global dataset of statistically downscaled CMIP6 models for climate impact analyses.

A large number of historical simulations and future climate projections are available from Global Climate Models, but these are typically of coarse resolution, which limits their effectiveness for assessing local scale changes in climate and attendant impacts. Here, we use a novel statistical downscaling model capable of replicating extreme events, the Bias Correction Constructed Analogues with Quantile mapping reordering (BCCAQ), to downscale daily precipitation, air-temperature, maximum and minimum temperature, wind speed, air pressure, and relative humidity from 18 GCMs from the Coupled Model Intercomparison Project Phase 6 (CMIP6). BCCAQ is calibrated using high-resolution reference datasets and showed a good performance in removing bias from GCMs and reproducing extreme events. The globally downscaled data are available at the Centre for Environmental Data Analysis ( https://doi.org/10.5285/c107618f1db34801bb88a1e927b82317 ) for the historical (1981-2014) and future (2015-2100) periods at 0.25° resolution and at daily time step across three Shared Socioeconomic Pathways (SSP2-4.5, SSP5-3.4-OS and SSP5-8.5). This new climate dataset will be useful for assessing future changes and variability in climate and for driving high-resolution impact assessment models.

EMBIO trial study protocol: left gastric artery embolisation for weight loss in patients living with obesity with a BMI 35-50 kg/m2.

INTRODUCTION: Left gastric artery embolisation (LGAE) is a well-established treatment for major upper gastrointestinal (GI) bleeding when control is not established via upper GI endoscopy and recently has shown promising results for weight loss in small single arm studies. LGAE could be a treatment option in between our current tier-3 and tier-4 services for obesity. EMBIO is a National Institute for Health Research funded trial, a multicentre double-blinded randomised controlled trial between Imperial College National Health Service Trust and University College London Hospital, comparing LGAE versus Placebo procedure. The key aims of the trial is to evaluate LGAE efficacy on weight loss, its mechanism of action, safety profile and obesity-related comorbidities. METHODS AND ANALYSIS: 76 participants will be recruited from the existing tier-3 database after providing informed consent. Key inclusion criteria include adults aged 18-70 with a body mass index 35-50 kg/m2 and appropriate anatomy of the left gastric artery and coeliac plexus on CT Angiogram. Key exclusion criteria included previous major abdominal and bariatric surgery, weight >150 kg, type 2 diabetes on any medications other than metformin and the use of weight modifying medications. Participants will undergo mechanistic visits 1 week prior to the intervention and 3, 6 and 12 months postintervention. Informed consent will be received from each participant and they will be randomised in a 1:1 ratio to left gastric artery embolisation and placebo treatment. Blinding strategies include the use of moderate doses of sedation, visual and auditory isolation. All participants will enter a tier-3 weight management programme postintervention. The primary analysis will estimate the difference between the groups in the mean per cent weight loss at 12 months. ETHICS AND DISSEMINATION: This trial shall be conducted in full conformity with the 1964 Declaration of Helsinki and all subsequent revisions. Local research ethics approval was granted by London-Central Research Ethics Committee, (Reference 19/LO/0509) on 11 October 2019. The Medicines and Healthcare products Regulatory Agency (MHRA) issued the Letter of No Objection on 8 April 2022 (Reference CI/2022/0008/GB). The trial's development and progress are monitored by an independent trial steering committee and data monitoring and ethics committee. The researchers plan to disseminate results at conferences, in peer- reviewed journals as well as lay media and to patient organisations. TRIAL REGISTRATION NUMBER: ISRCTN16158402.

Human papillomavirus infection and tumor microenvironment are associated with the microbiota in patients with oropharyngeal cancers-pilot study.

BACKGROUND: Previous microbiome studies of oropharyngeal cancer have shown that there are differences in the oral microbiota between human papillomavirus (HPV)-positive and HPV-negative patients. METHODS: We collected saliva, normal tissue, and tumor biopsies from 13 patients with oropharyngeal cancer (eight HPV-positive, five HPV-negative). We obtained basic clinical data from each patient. Extracted DNA was 16S rRNA gene sequenced. Analysis was based on HPV status and sample site using univariate, multivariate, and mixed effect regression methods. RESULTS: Multivariate analysis methods separated samples based on HPV status (Adonis, p < 0.001). Comparison of patients showed that there were significant changes in microbial richness across all sites based on HPV status (linear mixed effects regression, p = 0.0002). CONCLUSIONS: We found significant differences in overall microbial community and bacterial richness between oropharyngeal patients based on HPV status. Our results suggest that there are significant differences in the microbiome in patients with oropharyngeal cancer based on HPV status.

Impact of dams and climate change on suspended sediment flux to the Mekong delta.

The livelihoods of millions of people living in the world's deltas are deeply interconnected with the sediment dynamics of these deltas. In particular a sustainable supply of fluvial sediments from upstream is critical for ensuring the fertility of delta soils and for promoting sediment deposition that can offset rising sea levels. Yet, in many large river catchments this supply of sediment is being threatened by the planned construction of large dams. In this study, we apply the INCA hydrological and sediment model to the Mekong River catchment in South East Asia. The aim is to assess the impact of several large dams (both existing and planned) on the suspended sediment fluxes of the river. We force the INCA model with a climate model to assess the interplay of changing climate and sediment trapping caused by dam construction. The results show that historical sediment flux declines are mostly caused by dams built in PR China and that sediment trapping will increase in the future due to the construction of new dams in PDR Lao and Cambodia. If all dams that are currently planned for the next two decades are built, they will induce a decline of suspended sediment flux of 50% (47-53% 90% confidence interval (90%CI)) compared to current levels (99 Mt/year at the delta apex), with potentially damaging consequences for local livelihoods and ecosystems.

The small-deflection energy analyzer (SDEA): Enabling multi-point investigations in the thermosphere-ionosphere.

The Small-Deflection Energy Analyzer (SDEA), a new type of parallel plate analyzer of high sensitivity and resolution, enables CubeSat applications for new ionosphere-thermosphere investigations. SDEA's data of angle-energy distributions yield the thermosphere-ionosphere parameters of neutral wind and ion-drift vectors with corresponding temperatures and densities. Less than 4 cm in total length and 2 cm on the side, SDEA is used in the wind-temperature and ion-drift temperature spectrometers pair to provide two of the three instrument functions in the Wind-Ion-Neutral-Composition Suite now operating in three satellites in a low-Earth orbit. The small-deflection feature of SDEA allows miniaturization with several advantages discussed within. A description of SDEA is followed by examples of laboratory and a limited amount of flight data taken in low-Earth-orbit to demonstrate precision possible with SDEA. Strengths and weaknesses are discussed.

Genomic selection for white spot syndrome virus resistance in whiteleg shrimp boosts survival under an experimental challenge test.

White spot syndrome virus (WSSV) causes major worldwide losses in shrimp aquaculture. The development of resistant shrimp populations is an attractive option for management of the disease. However, heritability for WSSV resistance is generally low and genetic improvement by conventional selection has been slow. This study was designed to determine the power and accuracy of genomic selection to improve WSSV resistance in Litopenaeus vannamei. Shrimp were experimentally challenged with WSSV and resistance was evaluated as dead or alive (DOA) 23 days after infestation. All shrimp in the challenge test were genotyped for 18,643 single nucleotide polymorphisms. Breeding candidates (G0) were ranked on genomic breeding values for WSSV resistance. Two G1 populations were produced, one from G0 breeders with high and the other with low estimated breeding values. A third population was produced from "random" mating of parent stock. The average survival was 25% in the low, 38% in the random and 51% in the high-genomic breeding value groups. Genomic heritability for DOA (0.41 in G1) was high for this type of trait. The realised genetic gain and high heritability clearly demonstrates large potential for further genetic improvement of WSSV resistance in the evaluated L. vannamei population using genomic selection.

Ruptured abdominal aortic aneurysms in southern Saskatchewan: a 10-year mortality review.

The Regina Qu'Appelle Health Region (RQHR) provides all tertiary vascular care for southern Saskatchewan and portions of southwestern Manitoba. The present study was undertaken to determine the regional mortality rates following rupture of an abdominal aortic aneurysm and to compare these rates with the published literature. A retrospective chart review was undertaken on all cases of ruptured abdominal aortic aneurysms (rAAA) presenting to the RQHR between March 1, 1996, and February 28, 2006. The demographic data and clinical outcomes were collected from hospital charts by a single reviewer. Over the 10-year study period, 101 cases of rAAA were presented to the RQHR. Patient demographics and comorbidities were comparable to other studies in the published literature. Thirty-seven percent of patients presented with systolic blood pressure below 90 mm Hg, and 7% had no recordable blood pressure. The overall mortality was 25%. Mortality risk was not statistically different between patients presenting within Regina (30%) and those referred from a distance of more than 35 km (21%, P = .353). Seven patients were treated palliatively, and 94 proceeded to open surgical repair. Within the group of patients undergoing surgery, there was a 19% mortality rate. The data show a low observed mortality rate for rAAA presenting to the RQHR. The favorable outcome of the patients is not associated with preselection bias of patients transported long distances to specialist vascular care.

A randomised controlled trial of a duodenal-jejunal bypass sleeve device (EndoBarrier) compared with standard medical therapy for the management of obese subjects with type 2 diabetes mellitus.

INTRODUCTION: The prevalence of obesity and obesity-related diseases, including type 2 diabetes mellitus (T2DM), is increasing. Exclusion of the foregut, as occurs in Roux-en-Y gastric bypass, has a key role in the metabolic improvements that occur following bariatric surgery, which are independent of weight loss. Endoscopically placed duodenal-jejunal bypass sleeve devices, such as the EndoBarrier (GI Dynamics, Lexington, Massachusetts, USA), have been designed to create an impermeable barrier between chyme exiting the stomach and the mucosa of the duodenum and proximal jejunum. The non-surgical and reversible nature of these devices represents an attractive therapeutic option for patients with obesity and T2DM by potentially improving glycaemic control and reducing their weight. METHODS AND ANALYSIS: In this multicentre, randomised, controlled, non-blinded trial, male and female patients aged 18-65 years with a body mass index 30-50 kg/m2 and inadequately controlled T2DM on oral antihyperglycaemic medications (glycosylated haemoglobin (HbA1c) 58-97 mmol/mol) will be randomised in a 1:1 ratio to receive either the EndoBarrier device (n=80) for 12 months or conventional medical therapy, diet and exercise (n=80). The primary outcome measure will be a reduction in HbA1c by 20% at 12 months. Secondary outcome measures will include percentage weight loss, change in cardiovascular risk factors and medications, quality of life, cost, quality-adjusted life years accrued and adverse events. Three additional subgroups will investigate the mechanisms behind the effect of the EndoBarrier device, looking at changes in gut hormones, metabolites, bile acids, microbiome, food hedonics and preferences, taste, brain reward system responses to food, eating and addictive behaviours, body fat content, insulin sensitivity, and intestinal tissue gene expression. TRIAL REGISTRATION NUMBER: ISRCTN30845205, ClinicalTrials.gov Identifier NCT02459561.

Tear Interferon-Gamma as a Biomarker for Evaporative Dry Eye Disease.

Purpose: To assess whether tear hyperosmolarity, being diagnostic of dry eye disease (DED), is associated with specific alterations to the cytokine content of human tears that may provide a biomarker for DED. Methods: In this prospective, cross-sectional, clinical study, participants (n = 77) were recruited from a single clinical site and categorized into groups based upon tear osmolarity status (n = 62 hyperosmolar, n = 15 normo-osmolar). Comprehensive anterior eye clinical assessments were undertaken. Concentrations of seven cytokines (IL-2, IL-4, IL-6, IL-10, IL-17A, IFN-γ, and TNF-α) in basal tears were assayed using multiplex cytometric bead array. The main outcome measure was difference in cytokine concentration between groups. Group comparisons were undertaken using 2-tailed t-tests. Cohen's effect size was calculated for each finding. Spearman correlations between cytokine concentrations, clinical symptoms, and clinical parameters of DED were calculated. Results: Tear hyperosmolarity was specifically associated with increased tear IFN-γ levels (13.3 ± 2.0 vs. 4.4 ± 1.4 pg/mL, P = 0.03). Cohen's effect size was large (0.8) for changes to tear IFN-γ levels. Significant correlations were observed between IFN-γ concentration and each of: tear osmolarity (r = 0.34; P = 0.007), total ocular surface staining (r = 0.56, P < 0.0001), and Schirmer test score (r = -0.33, P = 0.003). Conclusions: Tear hyperosmolarity is specifically associated with higher levels of the proinflammatory cytokine IFN-γ, which correlate with key clinical parameters of DED. The calculated effect size (0.8) suggests that this assay has diagnostic power as a biomarker for evaporative DED.

Auranofin is a potent suppressor of osteosarcoma metastasis.

Osteosarcoma (OS) accounts for 56% of malignant bone cancers in children and adolescents. Patients with localized disease rarely develop metastasis; however, pulmonary metastasis occurs in approximately 50% of patients and leads to a 5-year survival rate of only 10-20%. Therefore, identifying the genes and pathways involved in metastasis, as new therapeutic targets, is crucial to improve long-term survival of OS patients. Novel markers that define metastatic OS were identified using comparative transcriptomic analyses of two highly metastatic (C1 and C6) and two poorly metastatic clonal variants (C4 and C5) isolated from the metastatic OS cell line, KHOS. Using this approach, we determined that the metastatic phenotype correlated with overexpression of thioredoxin reductase 2 (TXNRD2) or vascular endothelial growth factor (VEGF). Validation in patient biopsies confirmed TXNRD2 and VEGF targets were highly expressed in 29-42% of metastatic OS patient biopsies, with no detectable expression in non-malignant bone or samples from OS patients with localised disease. Auranofin (AF) was used to selectively target and inhibit thioredoxin reductase (TrxR). At low doses, AF was able to inhibit TrxR activity without a significant effect on cell viability whereas at higher doses, AF could induce ROS-dependent apoptosis. AF treatment, in vivo, significantly reduced the development of pulmonary metastasis and we provide evidence that this effect may be due to an AF-dependent increase in cellular ROS. Thus, TXNRD2 may represent a novel druggable target that could be deployed to reduce the development of fatal pulmonary metastases in patients with OS.