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.

A stabilizer-free method based on segmented flow for the continuous synthesis of TiO2 supported noble metal nanoparticles (M/TiO2-MR, M = Pd, Pt or Au) was proposed. Due to the enhanced mixing performance arising from the internal convection in the discrete plugs, the particle size of noble metal nanoparticles could be well controlled by reducing the metal precursors with NaBH4 just in the presence of TiO2 without using any stabilizer. In comparison with the batch method, the as-prepared M/TiO2-MR had smaller noble metal particle size and better dispersity. Experimental results showed that adjusting the oil-to-water phase ratio or increasing the total volume flow rate and synthetic temperature could lead to smaller average particle size with narrower distribution. The as-prepared M/TiO2-MR possessed higher catalytic activities in the hydrolysis of ammonia borane than those prepared by the batch method, which could be ascribed to smaller noble metal nanoparticles, exposing more active sites.

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.

A document by Lillian D. Parker, Ph.D., written on Authorea.

A document by Lillian D. Parker, Ph.D., written on Authorea.

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.

Species with broader niches may have the opportunity to occupy larger geographic areas, assuming no limitations on dispersal and a relatively homogeneous environmental space. While there is general support for positive \textit{geographic range size – climatic niche area} relationships, a great deal of variation exists across taxonomic and spatial gradients. Here, we use data on a large set of mammal ($n$ = 1225), bird ($n$ = 1829), and tree ($n$ = 341) species distributed across the Americas to examine the \textbf{1}) relationship between geographic range size and climatic niche area, \textbf{2}) influence of species traits on species departures from the best fit geographic range size – climatic niche area relationship, and \textbf{3}) how detection of these relationships is sensitive to how species range size and climatic niche area are estimated. We find positive \textit{geographic range size – climatic niche area} relationships for all taxa. Residual variation in this relationship contained a strong latitudinal signal. Subsampling the occurrence data to create a null expectation, we found that residual variation did not strongly deviate from the null expectation. Together, we provide support for the generality of \textit{geographic range size – climatic niche area} relationships, which may be constrained by latitude but are agnostic to species identity, suggesting that species traits are far less responsible than geographic barriers and the distribution of land area and available environmental space.

We report an uncommon case of late infective endocarditis, in a patient with a history of intravenous drug abuse and HIV positivity, 9 years after a percutaneous closure of a patent foramen ovale. Despite a target and prolonged intravenous antibiotic therapy, he was then referred for surgical device and vegetation removal. Given the high risk associated with drug addiction lifestyle, especially in HIV positive cases, it is mandatory to observe this group of patients with lifelong follow-up and support. Furthermore, it may be considered a multidisciplinary-team approach to find the best option for these patients, also evaluating a surgical correction.

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.

Introduction: Raynaud phenomenon (RP) is a multifactorial disorder. If any underlying disease cannot be detected responsible for RP then it considered as primary RP (pRP). We aimed to investigate the differences between laboratory markers and impaired endothelial function in pRP. Material and Methods: Forty-two pRP patients included as study and control groups were created from 30 healthy individuals. The endothelial function was evaluated with flow-mediated dilatation (FMD) of the brachial artery. The blood samples were obtained both groups and white blood cell [WBC], hemoglobin, platelet, mean platelet volume [MPV], creatinine, alanine aminotransferase [ALT], aspartate aminotransferase[AST], D-dimer, fibrinogen, albumin, fibrinogen to albumin ratio [FAR], Neutrophil to Lymphocyte ratio [NLR], D-dimer to albumin ratio [DDAR] and monocyte chemo-attractant protein-1 [MCP-1]. Obtained blood parameters and FMD values were compared between groups. Results: The groups were found as similar in regards to age, gender, smoking history (p<0.05). There was no difference between the two groups in regards to hemoglobin, platelet, MPV, creatinine, ALT, D-dimer, albumin, FAR, NLR, DDAR levels (p<0.05). AST levels were slightly higher in pRP group (p=0.027). Markedly increased WBC, fibrinogen, MPV and MCP-1 values were detected in pRP group (p=0.000). Additionally, higher abnormal FMD responses were detected in pRP group (p=0.000). There was a direct correlation between abnormal FMD response and serum MCP-1 values in patients with pRP (R: 0.308, R2: 0.095, p: 0.044). Conclusion: It seems to be that MCP-1 levels are higher in patients with pRP and increased values of MCP-1 levels seem to be related to impaired endothelial functions

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.

Perioperative management of congenital tracheal stenosis (CTS) is challenging. Objectives: We investigated the effect of closed-pediatric intensive care unit (PICU) perioperative management by pediatric intensivists, compared with open-PICU management by surgeons, on the ventilator-free days (VFD) and length of postoperative PICU stay in children with CTS. Methods: This retrospective cohort study was conducted in a PICU in Japan. Children with CTS who underwent slide tracheoplasty were grouped according to whether they were perioperatively managed in an open (January 2015 to April 2016) or a closed (May 2016 to July 2019) PICU. Data were extracted from patient medical records. Results: In total, 13 and 38 patients were included in the open- and closed-PICU groups, respectively. Compared to the open-PICU group, the closed-PICU group had shorter durations of muscle relaxant administration (median: 4 vs. 5 days; P < 0.001); earlier initiation of enteral feeding (median: postoperative day 1 vs. postoperative day 7; P < 0.001); more 28-day VFD (median: 21 vs. 20 days; P = 0.04); and shorter duration of postoperative PICU stay (median: 16 vs. 36 days; P = 0.002), but the mortality did not differ significantly (0/38 [0%] vs. 1/13 [8%]; P = 0.25). Conclusions: Closed-PICU perioperative management with pediatric intensivists’ participation significantly increased 28-day VFD and reduced the length of postoperative PICU stay in patients with CTS.

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: s.sholapurkar@nhs.netTel: 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 highly transmissible severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected more than 196 million people, claiming ~ 4.2 million lives to date. Although mandatory quarantines, lockdowns, and vaccinations help curb viral transmission, safe and effective preventative measures remain urgently needed. Here, we present a generic strategy for containing SARS-CoV-2 by cellulose materials. Specifically, we developed a bifunctional fusion protein consisting of a cellulose-binding domain and a nanobody (Nb) targeting the receptor-binding domain of SARS-CoV-2. The immobilization of the fusion proteins on cellulose substrates enhanced the capture efficiency of Nbs against SARS-CoV-2 pseudoviruses of both the wildtype and the D614G variant, the latter of which has been shown to confer higher infectivity. Furthermore, the fusion protein was integrated into a customizable chromatography with highly porous cellulose for neutralizing virus from contaminated fluids in a continuous and cost-effective fashion. Taken together, our work leverages low-cost cellulose materials and recently developed Nbs to provide a complementary approach to addressing the pandemic.

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.

Introduction: A major focus in CF care aims to increase weight gain. Rates of overweight and obese people with CF have gradually increased over the past decade. Obesity could be a risk for restriction of lung volumes and airway obstruction as well as increase rates of pulmonary exacerbations in people with CF. Methods: Patients 6 years of age and older were categorized into weight categories based on the CDC definitions. A retrospective chart review was conducted to obtain lung function testing and other outcomes. Results: 107 patients with a median age of 20.6 years were included in this analysis. 8.4%, 64%, 18% and 10% of patients were underweight, normal/healthy weight, overweight and obese respectively. FEV1 and FVC (% predicted) did not differ between patients with weights in the normal range vs. patients in the overweight/obese categories. Linear regression analysis showed a direct correlation between BMI and FEV1 that continued as BMI entered overweight and obese categories in both pediatric and adult patients. Overweight/obese patients did not have increased rates of pulmonary exacerbations compared to those in the normal/healthy weight category. Conclusion: As CF therapies continue to improve, an increasing number of people with CF are exceeding the CDC’s normal weight range. Gaining weight past the normal range does not appear to negatively impact pulmonary health of people with CF. If this trend of increased weight gain continues, it remains to be seen if it will eventually negatively affect lung health.

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.

Investment in the stock market is currently very popular due to its economic gain. Therefore, numerous researchers and academicians work is focused on financial time series prediction due to its data availability and profitability. Based on the literature it can be seen that various versions of the AdaboostM1 algorithm have been applied in the stock market either by tuning the algorithm parameters or attempting various base learners but the accuracy has not yet reached to favorable and reliable level. Therefore, this study proposes an improved version of AdaboostM1(ADA), which is implemented in the Waikato Environment for Knowledge Analysis(WEKA) to predict stock market prices based on historical data. The improved AdaBoostM1 integrates the set of Multilayer Perceptron (MLP) predictors instead of using DecisionStumps, which is normally being applied. The enhanced AdaBoostM1 is named Adaboost with Multilayer Perceptron (ADA-MLP). As the result, the ADA-MLP was found to be outperforming the original ADA by 1.52%, in which the ADA-MLP achieved the CA of 100% on average while the ADA achieved 98.48%. Furthermore, the ADA-MLP was al