High dimensional models typically require a large computational overhead for multiphysics applications, which hamper their use for broad-sweeping domain interrogation. Herein, we develop a modeling framework to capture the through-plane fluid dynamic response of electrodes and flow fields in a redox flow cell, generating a computationally inexpensive two-dimensional (2D) model. We leverage a depth averaging approach that also accounts for variations in out-of-plane fluid motion and departures from Darcy’s law that arise from averaging across three-dimensions (3D). Our Resulting depth-averaged 2D model successfully predict the fluid dynamic response of arbitrary in-plane flow field geometries, with discrepancies of < 5% for both maximum velocity and pressure drop. This corresponds to reduced computational expense, as compared to 3D representations (< 1% of duration and 10% of RAM usage), providing a platform to screen and optimize a diverse set of cell geometries.

Purpose: The aim of this study was to evaluate the diagnostic accuracy of 18-fluorodeoxyglucose-positron emission tomography (18F-FDG-PET) and positron emission tomography/computed tomography (PET/CT) in imaging primary and metastatic lesions in Ewing sarcoma (ES). Methods: PubMed, Cochrane, Scopus, and Web of Science were searched for relevant studies. Data concerning 18F-FDG-PET/CT diagnostic accuracy were extracted and then analysed using Open Meta-analyst software. Reported diagnostic accuracy outcomes included sensitivity, specificity, negative likelihood ratio (NLR), positive likelihood ratio (PLR), and diagnostic odds ratio. Results: 31 studies with a total of 735 patients were included in this meta-analysis. The sensitivity and specificity of 18F-FDG PET/CT were: 92.6% and 74.1% for total ES lesions, 96.7% and 68.3% for ES primary lesions, 76.1% and 92.4% for lung metastasis, 83.9% and 93.2% for bone metastasis and 89.9% and 92.6% for ES recurrence respectively. Conclusion: 18F-FDG PET/CT is sensitive and accurate in diagnosing, staging, and detecting the recurrence of ES compared to non-PET imaging. It has high specificity for diagnosing recurrence of ES as well as lung and bone metastases.

Background: Primary immunodeficiency diseases (PIDs) comprise more than 400 rare diseases with potential life-threatening conditions. Clinical manifestations and genetic defects are heterogeneous and diverse among populations. Here, we aimed to characterize the clinical, immunological and genetic features of Thai pediatric patients with PIDs. The use of whole exome sequencing (WES) in diagnosis and clinical decision making was also assessed. Methods: 36 unrelated patients with clinical and laboratory findings consistent with PIDs were recruited from January 2010 to December 2020. WES was performed to identify the underlying genetic defects. Results: The median age of disease onset was 4 months (range; 1 month to 13 years) and 24 were male (66.7%). Recurrent sinopulmonary tract infection was the most common clinical presentation followed by septicemia, and severe pneumonia. Using WES, we successfully identified the underlying genetic defects in 18 patients (50%). Of the 20 variants identified, six have not been previously described (30%). According to the International Union of Immunological Societies (IUIS), 38.9% of these detected cases (7/18) were found to harbor variants associated with genes in combined immunodeficiencies with associated or syndromic features (Class II). Conclusion: The diagnostic yield of WES in this patient cohort was 50%. Six novel genetic variants in PID genes were identified. The clinical usefulness of WES in PIDs was demonstrated, emphasizing it as an effective diagnostic strategy in these genetically heterogeneous disorders.

Behcet's Disease is a rare systemic vasculitis characterized by recurrent episodes of acute inflammation affecting blood vessels of all sizes. Symptoms include orogenital apthosis, cutaneous skin lesions, and uveitis. We present the case of a 38-year-old Nepalese man with Behcet's Disease. In Nepal, Behcet's Disease may still be under-reported.

Machine learning (ML) models are valuable research tools for making accurate predictions. However, ML models often unreliably extrapolate outside their training data. We propose an uncertainty quantification method for ML models (and generally for other nonlinear models) with parameters trained by least squares regression. The uncertainty measure is based on the multiparameter delta method from statistics, which gives the standard error of the prediction. The uncertainty measure requires the gradient of the model prediction and the Hessian of the loss function, both with respect to model parameters. Both the gradient and Hessian can be readily obtained from most ML software frameworks by automatic differentiation. We show that the uncertainty measure is larger for input space regions that are not part of the training data. Therefore this method can be used to identify extrapolation and to aid in selecting training data or assessing model reliability.

Background: Bicuspid aortic valve is the most common congenital heart defect and predisposes patients to developing aortic stenosis more frequently and at a younger age than the general population. However, the influence of bicuspid aortic valve on the rate of progression of aortic stenosis remains unclear. Methods: In 236 patients (177 tricuspid aortic valve, 59 bicuspid aortic valve) matched by initial severity of mild or moderate aortic stenosis, we retrospectively analyzed baseline echocardiogram at diagnosis with latest available follow-up echocardiogram. Baseline comorbidities, annualized progression rate of hemodynamic parameters, and hazard of aortic valve replacement were compared between valve phenotypes. Results: Median echocardiographic follow-up was 2.6 (IQR 1.6-4.2) years. Patients with tricuspid aortic stenosis were significantly older with more frequent comorbid hypertension and congestive heart failure. Median annualized progression rate of mean gradient was 2.3 (IQR 0.6-5.0) mmHg/year vs. 1.5 (IQR 0.5-4.1) mmHg/year (p=0.5), and that of peak velocity was 0.14 (IQR 0-0.31) m/s/year vs. 0.10 (IQR 0.04-0.26) m/s/year (p=0.7) for tricuspid vs. bicuspid aortic valve, respectively. On multivariate analyses, bicuspid aortic valve was not significantly associated with more rapid progression of aortic stenosis. In a stepwise Cox proportional hazards model adjusted for baseline mean gradient, bicuspid aortic valve was associated with increased hazard of aortic valve replacement (HR: 1.7, 95% CI [1.0, 3.0], p=0.049). Conclusion: Bicuspid aortic valve may not significantly predispose patients to more rapid progression of mild or moderate aortic stenosis. Guidelines for echocardiographic surveillance of aortic stenosis need not be influenced by valve phenotype.

Background: For diseases with a genetic cause genomics can deliver improved diagnostics and facilitate access to targeted treatments. Drug pharmacodynamics and pharmacokinetics are often dependent on genetic variation underlying these processes. As pharmacogenomics comes of age it may be the first way in which genomics is utilised at a population level. Still required is guidance and standards of how genomic information can be communicated within the health record, and how clinicians should be alerted to variation impacting the use of medicines. Methods: The Professional Record Standards Body commissioned by National Health Service England developed guidance on using pharmacogenomics information in clinical practice. We conducted research with those implementing pharmacogenomics in England and internationally to produce guidance and recommendations for a systems-based approach. Results: A consensus viewpoint is that systems need to be in place to ensure the safe provision of pharmacogenomics information that is curated, actionable and up-to-date. Standards should be established with respect to notification and information exchange, which could impact new or existing prescribing and these must be in keeping with routine practice. Alerting systems should contribute to safer practices. Conclusion: Ensuring pharmacogenetics information is available to make use of medicines safer will require major effort of which this guidance is a beginning. Standards are required to ensure useful genomic information within the health record can be communicated to clinicians in the right format and times to be actioned successfully. A multidisciplinary group of stakeholders must be engaged in developing pharmacogenomic standards to support the most appropriate prescribing.

Primary bladder amyloidosis is a rare pathological finding. The clinical importance of this finding is that it may clinically mimic bladder cancer. The only accurate diagnostic method available till now is the histopathologic examination of tissue samples usually obtained through transurethral resection.

Respiratory Syncytial Virus (RSV) is a common seasonal respiratory virus and an important cause of illness among infants, but the burden of RSV disease is not well described among the older population. The objective of this study was to estimate the age-specific incidence of hospital admission among over 65s due to respiratory illnesses attributable to RSV in England to inform optimal vaccine and therapeutic interventions. We used linear multiple regression to examine the effect of changes in weekly counts of respiratory pathogens on the weekly counts of respiratory hospital admissions. The study population was all patients aged 65 years or over admitted to English hospitals between 2nd August 2010 and 30th July 2017. RSV was estimated to account for a seasonal annual average of 71 (95% CI 52-90) respiratory admissions per 100,000 in adults age 65-74 and 251 (95% CI 186-316) admissions per 100,000 adults age 75+. Pneumococcus was the pathogen responsible for highest annual average respiratory admission with 448 (95% CI 310-587) admissions per 100,000 adults age 65-74 and 1010 (95%CI 527-1493) admissions per 100,000 adults aged 75+. This study shows that RSV continues to exert a significant burden of disease among older adults in England. These findings will support development of policy for the use of RSV therapeutics and vaccines in this age group.

Vertebrate colonization of land occurred multiple times, including over 50 origins of terrestrial eggs in frogs. Some environmental factors and phenotypic responses that facilitated these transitions are known, but responses to water constraints and risk of ammonia toxicity during early development are poorly understood. We tested if ammonia accumulation and dehydration risk induce a shift from ammonia to urea excretion during in early stages of four anurans, from three origins of terrestrial development. We quantified ammonia and urea concentrations during early development on land, under well-hydrated and dry conditions. Where we found urea excretion, we tested for a plastic increase under dry conditions and with ammonia accumulation in developmental environments. We assessed the potential adaptive role of urea excretion by comparing ammonia tolerance measured in 96h-LC50 tests with ammonia levels in developmental environments. Ammonia accumulated in foam nests and perivitelline fluid, increasing over development and reaching higher concentrations under dry conditions. All four species showed high ammonia tolerance, compared to fishes and aquatic-breeding frogs. Both nest-dwelling larvae of Leptodactylus fragilis and late embryos of Hyalinobatrachium fleischmanni excreted urea, showing a plastic increase under dry conditions. These two species can develop the longest on land and urea excretion appears adaptive, preventing their exposure to potentially lethal levels of ammonia. Neither late embryos of Agalychnis callidryas nor nest-dwelling larvae of Engystomops pustulosus risked toxic ammonia levels under dry conditions, and neither excreted urea. Our results suggests that an early onset of urea excretion, its increase under dry conditions, and elevated ammonia tolerance, can all help prevent ammonia toxicity during terrestrial development. High ammonia represents a general risk for development that can be exacerbated as climate change increases dehydration risk for terrestrial-breeding frogs. It may also be a cue that elicits adaptive physiological responses during early development.

Time series data are often observed in ecological monitoring. Frequently such data exhibit nonlinear trends over time potentially due to complex relationships between observed and auxiliary variables, and there may also be sudden declines over time due to major disturbances. This poses substantial challenges for modelling such data and also for model-based adaptive monitoring. We propose novel methods for finding adaptive designs for monitoring when historical data show such nonlinear patterns and sudden declines over time. This work is motivated by a coral reef monitoring program that has been established at Scott Reef; a coral reef off the Western coast of Australia. Data collected for monitoring the health of Scott Reef are considered, and semiparametric and interrupted time series modelling approaches are adopted to describe how these data vary over time. New methods are then proposed that enable adaptive monitoring designs to be found based on such modelling approaches. These methods are then applied to find future monitoring designs at Scott Reef and form a set of recommendations for future monitoring. Through applying the proposed methods, it was found that future information gain is expected to be similar across a variety of different sites, suggesting that no particular location needed to be prioritised at Scott Reef for the next monitoring phase. In addition, it was found that omitting some sampling sites/reef locations was possible without substantial loss in expected information gain, depending upon the disturbances that were observed. The resulting adaptive designs are used to provide recommendations for future monitoring in this region, and for reefs where changes to the current monitoring practices are being sought. Furthermore, as the methods used and developed throughout this study are generic in nature, this research has the potential to improve ecological monitoring more broadly where complex data are being collected over time.

As social media becomes an ever-increasing staple of everyday life and a growing percentage of people turn to community driven platforms as a primary source of information, the data created from these posts can provide a new source of information from which to better understand an event in near real-time. The 2018-2020 outbreak of virulent Newcastle Disease (vND) in Southern California is the third outbreak of vND in Southern California within a 50-year time span. These outbreaks are thought to be primarily driven by non-commercial poultry (i.e. backyard and game fowl) in the region. Here we employed a commercial “web crawling” tool between June of 2018 and July of 2020 which encompassed the majority of the outbreak in order to collect all available online mentions of virulent Newcastle Disease (vND) in relation to the outbreak. A total of 2,498 posts in English and Spanish were returned using a Boolean logic-based string search. While the number of posts was relatively small, their impact as measured by the number of visitors to the website and the number of people viewing the post (where provided) was much larger. Using views as a metric, Twitter was identified as the most significant source of comments over blogs, forums and other news sites. Posts with negative sentiment were found to have a larger audience relative to posts with a positive sentiment. In addition, posts with negative sentiment peaked in May of 2019 which preceded the formation of the anti-depopulation group Save Our Birds (SOB). As the usage and impact of social media grows, the ability to utilize tools to analyze social media may improve both response and outreach-based strategies for various disease outbreaks including vND in Southern California which has a large non-commercial poultry population.

Objectives. Fifteen potentially low value practices in adult orthopaedic trauma care were previously identified in a scoping review. The aim of this study was to synthesize the evidence on these practices. Methods. We searched four databases for systematic reviews, randomized controlled trials (RCTs), cohort studies and case series that assessed the effectiveness of selected practices. Methodological quality was evaluated using the Measurement Tool to Assess Systematic Reviews version 2 (AMSTAR-2) for systematic reviews and the Critical Appraisal Checklist for Case Series. We evaluated risk of bias with the Cochrane revised tool for RCTs and the risk of bias in non-randomized studies of interventions tool for observational studies. We summarized findings with measures of frequency and association for primary outcomes. Results. Of the 30,670 records screened, 70 studies were retained. We identified high-level evidence of lack of effectiveness or harm for routine initial imaging of ankle injury, orthosis for A0-A3 thoracolumbar burst fracture in patients < 60 years of age, cast or splint immobilization for suspected scaphoid fracture negative on MRI or confirmed fifth metacarpal neck fracture, and routine follow-up imaging for distal radius and ankles fractures. However, evidence was mostly based on studies of low methodological quality or high risk of bias. Conclusion. In this review, we identified clinical practices in orthopedic injury care which are not supported by current evidence and whose use may be questioned. In future research we should measure their frequency, assess practice variations and evaluate root causes to identify practices that could be targeted for de-implementation.

We report a rare case of postoperative recurrence of MLS in the left thigh with ectopic and metachronous pericardial metastases. He was found to have a cardiac abnormality that was initially thought to be a pericardial cyst, but was later pathologically confirmed to be MLS metastasis.

Letter to the Editor, BJOG Title:Prophylactic negative wound pressure dressing (NWPD) after caesarean – an extended debate to include surgical aspectsRe: Hyldig N, Joergensen JS, Lamont RF, Moller S, Vinter CA. Prophylactic negative pressure wound therapy in obese women undergoing caesarean section: a commentary on new evidence that fuels the debate. BJOG 2021; https://doi.org/10.1111/1471-0528.16750.Author: Mr. Shashikant L SHOLAPURKARMD, DNB, MRCOGDept of Obstetrics & Gynaecology,Royal United Hospital, Bath, BA1 3NG, UKEmail: [email protected]: 07906620662Word count: 500Corresponding Author: Mr. Shashikant L SHOLAPURKARMD, DNB, MRCOGDept of Obstetrics & Gynaecology,Royal United Hospital, Bath, BA1 3NG, UKStatement of interest: The author has no conflict of interest or funding to declare.

The urgent desire for Halon substitution propels the exploration of potential alternatives, because of the severe damage of Halons to the stratospheric ozone layer. In this paper, the thermal decomposition mechanism, as well as fire-extinguishing mechanism and performance of Trifluoroiodomethane (CF3I) were studied by density functional theory (DFT) calculation and experimental measurements, to analyze the practicability of this proposed Halon substitute. The thermal decomposition products of CF3I can react with active OH· and H· radicals to achieve the purpose of rapidly fire-extinguishing. Besides, through DFT calculation and reaction kinetics analysis, the fire-extinguishing radicals CF3· and I· are more easily generated during the interaction between CF3I and flame, which indicates the chemical- extinguishing mechanism and pronounced fire-extinguishing performance of CF3I. To explore its actual fire-extinguishing effect, the fire-extinguishing concentration (FEC) of CF3I was measured in cup burner. The FEC value of this proposed Halon substitute is 3.42vol% for extinguishment of methane-air flame, which is smaller than those of three HFCs and HFO-1336mzz(Z) and is comparable to that of Halon 1301. These findings suggest the promising applicability of CF3I in practical Halon replacement and the necessity of further evaluation.

Buried bumper syndrome (BBS) is a rare serious late complication of percutaneous endoscopic gastrostomy (PEG) where the internal bumper migrates along the stoma tract. BBS is a clinical diagnosis and the role of imaging is to identify the exact site of the migrated internal bumper.

Necrolytic Migratory Erythema (NME) is a rare cutaneous paraneoplastic manifestation of glucagonoma. We report a case of a woman with a 6-year history of delayed diagnosis of Glucagonoma. This case highlights the atypical clinical features of NME which makes the diagnosis difficult.