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For infants with the most severe forms of chronic lung disease, regardless of etiology, chronic mechanical ventilation can provide stability, reduce acute respiratory events, and alleviate increased work of breathing. This approach prioritizes the baby's growth and development during early life. Once breathing comfortably, these infants can tolerate developmental therapies with the goal of achieving the best neurocognitive outcomes possible.

Radar sensing offers a method of achieving 24‐h all‐weather drone surveillance, but in order to be maximally effective, systems need to be able to discriminate between birds and drones. This work examines drone‐bird classification performance as a function of signal to noise ratio (SNR). Classification at low SNR values is necessary in order to classify drones with a small radar cross‐section (RCS), as well as to facilitate reliable classification at longer ranges. To investigate the relationship between classification performance and SNR, Gaussian noise is added to an experimentally obtained dataset of radar spectrograms. Classification is performed by convolutional neural networks (CNNs). It is shown that for the data available classification accuracy drops with falling SNR, as might be expected for any given CNN. The degree to which performance degrades with reduced SNR is presented. It is further shown that simpler network architectures are more robust to noise. Finally, it is demonstrated that data augmentation can be used as a means of enhancing classification accuracy at lower SNR values. Bayesian optimisation is used to find the optimal augmentation hyperparameters and overall, classification accuracies of 92% are achieved at low SNR.

Although survival has improved dramatically for extremely preterm infants, those with the most severe forms of bronchopulmonary dysplasia (BPD) fail to improve in the neonatal period and go on to develop chronic respiratory failure. When careful weaning of respiratory support is not tolerated, the difficult decision of whether or not to pursue chronic ventilation via tracheostomy must be made. This requires shared decision-making with an interdisciplinary medical team and the child's family. Although they suffer from increased morbidity and mortality, the majority of these children will survive to tolerate ventilator liberation and tracheostomy decannulation. Care coordination for the technology-dependent preterm infant is complex, but there is a growing consensus that chronic ventilation can best support neurodevelopmental progress and improve long-term outcomes.

INTRODUCTION Bronchopulmonary dysplasia (BPD) is a common respiratory sequelae of preterm birth, for which longitudinal outpatient data are limited. Our objective was to describe a geographically diverse outpatient cohort of former preterm infants followed in BPD-disease specific clinics. METHODS Seven BPD specialty clinics contributed data using standardized instruments to this retrospective cohort study. Inclusion criteria included preterm birth (

As the phase III COVID‐19 vaccine trials excluded patients on immunosuppressive treatments, or patients with significant autoimmunity, the Australasian Medical Dermatology Group make the following preliminary recommendations around COVID‐19 vaccination in dermatology patients on immunomodulatory and/or biologic agents. Vaccination against COVID‐19 is strongly encouraged for all patients on immunomodulatory drugs and/or biologic agents.There are currently insufficient data to recommend one COVID‐19 vaccine or vaccine type (mRNA, recombinant, inactivated virus) over another.No specific additional risk in patients on immunomodulatory or biologic therapies has so far been identified.Data on vaccine efficacy in patients on immunomodulatory or biologic therapies are missing, so standard vaccination protocols are recommended until otherwise advised.

Globally, collapse of ecosystems—potentially irreversible change to ecosystem structure, composition and function—imperils biodiversity, human health and well‐being. We examine the current state and recent trajectories of 19 ecosystems, spanning 58° of latitude across 7.7 M km2, from Australia's coral reefs to terrestrial Antarctica. Pressures from global climate change and regional human impacts, occurring as chronic ‘presses’ and/or acute ‘pulses’, drive ecosystem collapse. Ecosystem responses to 5–17 pressures were categorised as four collapse profiles—abrupt, smooth, stepped and fluctuating. The manifestation of widespread ecosystem collapse is a stark warning of the necessity to take action. We present a three‐step assessment and management framework (3As Pathway Awareness, Anticipation and Action) to aid strategic and effective mitigation to alleviate further degradation to help secure our future.

This study describes a cognitive radar architecture with application to real‐time obstacle avoidance in mobile robotic platforms. The concept of a world memory map is introduced as a means of providing an enhanced perception of the environment around the robotic platform. This is combined with a specially designed obstacle avoidance algorithm, Nearest Steering Vector Searching, all capable of operating in real‐time. The study analytically derives the radar signal processing algorithm, starting from range‐angle maps, so that a collision free course to a set destination point can be robustly navigated. Finally, the performance of this cognitive approach is examined through a number of proof‐of‐concept experiments using a commercial off‐the‐shelf radar mounted on a mobile ground robotic platform.

While a wide range of treatments exist for actinic keratosis and skin field cancerisation, the long‐term benefits of the most common topical therapies are poorly defined. This report reviews the efficacy of the most commonly used topical therapies to treat regional or field lesions. Limited clinical and histopathological data are available on clearance rates at 12 months post‐treatment for the most commonly used agents, with varied outcome measures making any comparison difficult. In general, total field clearance rates at 12 months are suboptimal for the most commonly employed agents. Given the increasing incidence of actinic keratosis and skin field cancerisation due to an ageing population, further research into the efficacy of therapies is critical to guide treatment choice.

The stage history of Shakespeare's The Winter's Tale reflects changing critical perceptions about its themes as well as an evolution of theatrical production over a span of four centuries. First noted in astrologer Simon Forman's record of a performance on May 15, 1611, the play was popular with court audiences but disappeared from the stage when the theatres were closed at mid-century. It reappeared in a truncated performance on January 15, 1741. Nine months later David Garrick offered his abbreviated text—essentially a maudlin, three-act pastoral diversion—to popular appeal but critical censure. In 1802, John Philip Kemble's production presented a fuller, though Bowdlerized, text, featuring the great Sarah Siddons as Hermione. Hermione's role increasingly reflected the Victorian image of the selfless spouse who maintains her moral fiber under duress. During Charles Kean's directorship at the Princess's Theatre starting in 1850, the play acquired more lavish sets and scenery intended to reflect the historical context of the action, but the text sank under the weight of such ponderous efforts at realism. With the arrival of Harley Granville Barker's 1912 production at the Savoy Theatre, the play was returned to a more Elizabethan identity; a smaller, less cluttered stage permitted a faster-paced production with greater attention paid to Leontes as a psychologically fragile husband and monarch. This emphasis on the play as a study of the troubled marriage of a troubled king has persisted into the twentieth century as directors such as Jane Howell and Gregory Doran have lent this romance a convincing emotional depth.

Many research studies seek to identify the social determinants of health and occupation is an important predictor, both at the level of the individual as well as for populations. Whereas job titles are usually solicited during interviews or by questionnaire, before being able to use this information the responses need to be categorized using a coding system, such as the Canadian National Occupational Classification (NOC). Manual coding is the usual method, which is a time-consuming and error-prone activity with variable or inconsistent outcomes from teams of coders. In recent work the ACA-NOC algorithm1 was developed to perform automated coding based on matching job title text with the NOC’s job titles and textual descriptions. This algorithm was benchmarked on a small sample manually coded data set with subject matter experts subsequent review of coding discrepancies to facilitate functional improvements to the algorithm. Performance levels achieved illustrated the viability of the approach albeit larger benchmarking data sets were required. CanPATH2has collected data from approximately 330,000 volunteer Canadians, including information about health, lifestyle, occupation, environment and behavior. We report on the further benchmarking and further development of this algorithm in CanPATH funded project using over 60,000 manually coded job titles from the constituent Alberta Tomorrow Project. The algorithm was also applied to over 100,000 un-coded job titles from Atlantic PATH, including the Core questionnaire and occupational history data. The core outcome of the project identified that auto-coding results are comparable to manual coding in accuracy and superior in speed e.g. 2 years of manual coding (64,000 records) can be auto coded in 72 hours. The algorithm was considered ready for deployment in operational settings: point of care, decision support for manual coders. Additional insights gained during the project revealed that (i) NOC and ATP data sets have a distribution bias where some NOC categories were over or under-represented and numerous non-standard lexical features were found in job titles and NOC job descriptions, (ii) benchmarking datasets from ATP included coding errors that were corrected by expert coders leading to the creation of gold standard test sets for further algorithm improvement studies, (iii) a study on 17 categories of occupations initially difficult to code, identified some job categories with near 90% coding accuracy. Automated coding of job titles to the NOC has been shown to be both practicable to good levels of accuracy and shown to significantly accelerate manual coding efforts from years to autocoding in a matter of hours without decrease in accuracy. Autocoding can replace costly, error prone manual labor with accurate point-of-care auto-coding such that patient occupation information during healthcare encounters could now supplement existing administrative data sets in electronic health record systems. This data can be used better to understand the socioeconomic consequences of health conditions, advise patients about returning to work with a health condition, recognizing occupations at risk of disease e.g. as in the COVID-19 pandemic. References Bao H, Baker CJO, Adisesh A. Occupation coding of job titles: iterative development of an automated coding algorithm for the canadian national occupation classification (ACA-NOC). JMIR Form Res 2020 Aug 5;4(8):e16422. doi:10.2196/16422 CanPath the Canadian Partnership for Tomorrow Project. https://canpath.ca/ accessed: 01.09.2021

Objective To determine the frequency and risk factors that lead to the development of persistent TCF (tracheocutaneous fistula) formation in children following tracheostomy decannulation at our institution. Methods A retrospective chart review of all pediatric patients at Children's Hospital Colorado who underwent tracheostomy decannulation and were being followed between January 1, 2007 and December 31, 2013. TCF was defined as a persistent fistula six months following decannulation. We determined patient demographics, age at tracheotomy, primary indication for tracheotomy, tracheostomy-tube size, medical comorbidities, age at decannulation, date of TCF closure, and method of TCF closure. Results One hundred twenty-nine patients ranging from 51 days to 19 years of age underwent tracheostomy decannulation. 63 (49%) patients underwent surgical closure of TCF. Compared to those with spontaneous closure by multivariable analysis, those with surgical closure were younger at tracheostomy placement (p = 0.0002), had a tracheostomy for a longer duration (p = 0.0025), and were diagnosed with tracheobronchomalacia (p = 0.0051). The likelihood of spontaneous closure decreased over time. Tracheostomy tube internal diameter correlated with age (R = 0.64, p Conclusions Approximately 50% of pediatric tracheostomy stoma sites will close spontaneously. Development of a persistent TCF was associated with younger age at placement, longer duration of tracheostomy, and the presence of tracheobronchomalacia. These observations may help clinicians anticipate outcomes following tracheostomy decannulation in children.

Microfluidic instrumentation offers unique advantages in biotechnology applications including reduced sample and reagent consumption, rapid mixing and reaction times, and a high degree of process automation. As dimensions decrease, the ratio of surface area to volume within a fluidic architecture increases, which gives rise to some of the unique advantages inherent to microfluidics. Thus, manipulation of surface characteristics presents a promising approach to tailor the performance of microfluidic systems. Microfluidic valves are essential components in a number of small volume applications and for automated microfluidic platforms, but rigorous evaluation of the sealing quality of these valves is often overlooked. In this work, the glass valve seat of hybrid glass/PDMS microfluidic valves was surface modified with hydrophobic silanes, octyldimethylchlorosilane (ODCS) or (tridecafluoro-1,1,2,2-tetrahydrooctyl)dimethylchlorosilane (PFDCS), to investigate the effect of surface energy on electrical resistance of valves. Valves with ODCS- or PFDCS- modified valve seats both exhibited >70-fold increases in electrical resistance (>500 GΩ) when compared to the same valve design with unmodified glass valve seats (7 ± 3 GΩ), indicative of higher sealing capacity. The opening times for valves with ODCS- or PFDCS-modified valve seats was ca. 5x shorter compared to unmodified valve seats, whereas the closing time was up to 8x longer for modified valve seats, though the total closing time was ≤1.5 s, compatible with numerous microfluidic valving applications. Surface modified valves assemblies offered sufficient electrical resistance to isolate sub-pA current signals resulting from electrophysiology measurement of α-hemolysin conductance in a suspended lipid bilayer. This approach is well-suited for the design of novel microfluidic architectures that integrate fluidic manipulations with electrophysiological or electrochemical measurements.

Background/Objectives: Atopic dermatitis (AD) has significant negative impact on health-related quality of life, mood, sleep, work productivity and everyday activities. Research into the use of new drugs in the management of AD continues to develop, and international updates and recommendations have been published. However, questions remain in the Australian setting. This consensus aims to provide evidence-based insights and practical advice on the management of adult AD in Australia. Methods: A panel (five dermatologists and one clinical immunologist) met to review the literature, critically examine clinical questions of relevance to Australian healthcare practitioners and develop a series of recommendation statements. A consensus panel, comprising the initial panel plus nine additional members, used a 2-round Delphi voting process to determine a set of final guidance statements. Consensus: ≥75% agreement in the range 7–9. Results: Round 1 voting comprised 66 guidance statements. Of these, consensus was reached on 26, which were retained, and five were removed. The remainder (35) were modified and one new guidance statement was added for inclusion in round 2 voting. After round 2, consensus was reached on 35, which were retained, and one was removed (considered redundant). The 61 guidance statements upon which consensus was reached were then used to support a series of core consensus recommendations and a management flow chart. Conclusions: Expert consensus recommendations providing practical guidance of clinical relevance to specialists and primary care physicians in Australia have been developed. Dissemination of this guidance and evaluation of its impact on patient outcomes remain to be undertaken.

Biological and pharmaceutical analytes like liposomes, therapeutic proteins, nanoparticles, and drug-delivery systems are utilized in applications, such as pharmaceutical formulations or biomimetic models, in which controlling their size is often critical. Many of the common techniques for sizing these analytes require method development, significant sample preparation, large sample quantities, and lengthy analysis times. In other cases, such as DLS, sizing can be biased towards the largest constituents in a mixture. Therefore, there is a need for more rapid, sensitive, accurate, and straightforward analytical methods for sizing macromolecules, especially those of biological origin which may be sample-limited. Taylor dispersion analysis (TDA) is a sizing technique that requires no calibration and consumes only nL to pL sample volumes. In TDA, average diffusion coefficients are determined via the Taylor–Aris equation by characterizing band broadening of an analyte plug under well-controlled laminar flow conditions. Diffusion coefficient can then be interpreted as hydrodynamic radius (RH) via the Stokes–Einstein equation. Here, we offer a tutorial review of TDA, intended to make the method better understood and more widely accessible to a community of analytical chemists and separations scientists who may benefit from the unique advantages of this versatile sizing method. We first provide a tutorial on the fundamental principles that allow TDA to achieve calibration-free sizing of analytes across a wide range of RH, with an emphasis on the reduced sample consumption and analysis times that result from utilizing fused silica capillaries. We continue by highlighting relationships between operating parameters and critically important flow conditions. Our discussion continues by looking at methods for applying TDA to sample mixtures via algorithmic approaches and integration of capillary electrophoresis and TDA. Finally, we present a selection of reports that demonstrate TDA applied to complex challenges in bioanalysis and materials science.

Pharmacologic inhibition of the mammalian target of rapamycin (mTOR) in the setting of renal transplantation has previously been associated with lower human immunodeficiency virus 1 (HIV-1) DNA burden, and in vitro studies suggest that mTOR inhibition may lead to HIV transcriptional silencing. Because prospective clinical trials are lacking, we conducted an open-label, single-arm study to determine the impact of the broad mTOR inhibitor, everolimus, on residual HIV burden, transcriptional gene expression profiles, and immune responses in HIV-infected adult solid organ transplant (SOT) recipients on antiretroviral therapy. Whereas everolimus therapy did not have an overall effect on cell-associated HIV-1 DNA and RNA levels in the entire cohort, participants who maintained everolimus time-averaged trough levels >5ng/mL during the first 2months of therapy had significantly lower RNA levels up to 6months after the cessation of study drug. Time-averaged everolimus trough levels significantly correlated with greater inhibition of mTOR gene pathway transcriptional activity. Everolimus treatment also led to decreased PD-1 expression on certain T cell subsets. These data support the rationale for further study of the effects of mTOR inhibition on HIV transcriptional silencing in non-SOT populations, either alone or in combination with other strategies. Trial Registration: ClinicalTrials.gov NCT02429869.

Nanomechanical circuits for transverse acoustic waves promise to enable new approaches to computing, precision biochemical sensing and many other applications. However, progress is hampered by the lack of precise control of the coupling between nanomechanical elements. Here, we demonstrate virtual-phonon coupling between transverse mechanical elements, exploiting tunnelling through a zero-mode acoustic barrier. This allows the construction of large-scale nanomechanical circuits on a silicon chip, for which we develop a new scalable fabrication technique. As example applications, we build mode-selective acoustic mirrors with controllable reflectivity and demonstrate acoustic spatial mode filtering. Our work paves the way towards applications such as fully nanomechanical computer processors and distributed nanomechanical sensors, and to explore the rich landscape of nonlinear nanomechanical dynamics., 9 pages, 6 figures

The ability to tune the wavelength of light emission on a silicon chip is important for scalable photonic networks, distributed photonic sensor networks and next generation computer architectures. Here we demonstrate light emission in a chip-scale optomechanical device, with wide tunablity provided by a combination of radiation pressure and photothermal effects. To achieve this, we develop an optically active double-disk optomechanical system through implantation of erbium ions. We observe frequency tuning of photoluminescence in the telecommunications band with a wavelength range of 520 pm, green upconversion lasing with a threshold of $340\pm 70 \; \mu$W, and optomechanical self-pulsing caused by the interplay of radiation pressure and thermal effects. These results provide a path towards widely-tunable micron-scale lasers for photonic networks., Comment: Main text 7 pages, 5 figures; Appendix 4 pages, 4 figures

ObjectivesThe clinical impact of SARS-CoV-2 has varied across countries with varying cardiovascular manifestations. We review the cardiac presentations, in-hospital outcomes and development of cardiovascular complications in the initial cohort of SARS-CoV-2 positive patients at Imperial College Healthcare National Health Service Trust, UK.MethodsWe retrospectively analysed 498 COVID-19 positive adult admissions to our institute from 7 March to 7 April 2020. Patient data were collected for baseline demographics, comorbidities and in-hospital outcomes, especially relating to cardiovascular intervention.ResultsMean age was 67.4±16.1 years and 62.2% (n=310) were male. 64.1% (n=319) of our cohort had underlying cardiovascular disease (CVD) with 53.4% (n=266) having hypertension. 43.2%(n=215) developed acute myocardial injury. Mortality was significantly increased in those patients with myocardial injury (47.4% vs 18.4%, pConclusionHypertension, pre-existing CVD and acute myocardial injury were associated with increased in-hospital mortality in our cohort of COVID-19 patients. However, only a low number of patients required invasive cardiac intervention.

The COVID-19 pandemic has altered our approach to inpatient echocardiography delivery. There is now a greater focus to address key clinical questions likely to make an immediate impact in management, particularly during the period of widespread infection. Handheld echocardiography (HHE) can be used as a first-line assessment tool, limiting scanning time and exposure to high viral load. This article describes a potential role for HHE during a pandemic. We propose a protocol with a reporting template for a focused core dataset necessary in delivering an acute echocardiography service in the setting of a highly contagious disease, minimising risk to the operator. We cover the scenarios typically encountered in the acute cardiology setting and how an expert trained echocardiography team can identify such pathologies using a limited imaging format and include cardiac presentations encountered in those patients acutely unwell with COVID-19.

COVID-19 has highlighted potential shortcomings in our approach to psychological health that had perhaps become the accepted status quo within cardiology. Importantly, the pandemic may offer a unique opportunity to redress them. During 2020, physicians have had to question their ability to deliver optimal care with scarce resources, limited knowledge, concerns about personal safety and, by extension, the safety of one’s family. For some, these challenges may have a lasting psychological impact. Encouragingly, many staff have acknowledged the potential effect of these pressures on their mental health, making short-term adaptations and promoting staff camaraderie. However, achieving long-lasting changes in our approach to supporting those affected could create a positive legacy to this pandemic. The idea of ‘moral injury’, originally recognised within the military, describes the psychological distress which may follow ethical or moral beliefs being challenged. Such situations can lead to overwhelming feelings of culpability, shame or anger, which increase someone’s vulnerability to develop, or exacerbate, mental ill health including post-traumatic stress disorder (PTSD) and depression.1 The attribution of moral injury to healthcare workers during the pandemic is increasingly recognised.2 Equally important is the concept of post-traumatic growth,3 which recognises that most people will survive and psychologically develop following these unwished-for experiences. Evidence shows that good organisational structures, management and psychologically savvy teamwork can calibrate this and push the needle more towards growth and away from injury. Although moral injury in cardiology has yet to be substantiated, evidence suggests that cardiologists report some of the highest levels of burn-out and work longer hours than other physicians. However, only 23% report being willing to seek professional help for feelings of depression or suicidality.4 This may result from a stoicism existing within cardiology where a culture of appearing impervious to pressure prevails and is lauded, suggesting that many …

Introduction Medical errors can occur any time resident physicians transition between rotations, especially to unfamiliar areas such as subspecialty pediatrics. To combat this, we created and implemented the pediatric resident education in pulmonary (PREP) boot camp using Kern's six-step approach to curriculum development. Methods PREP was a 5-hour session with multiple high-yield components held on the first day of each new rotation, aimed to prepare residents to care for complex pulmonary inpatients, including those with tracheostomy and ventilator dependence, asthma, and cystic fibrosis. The curriculum was evaluated at multiple time points through surveys of residents and faculty and two formal resident focus group sessions. Results PREP was successfully implemented in July 2018 with continued monthly sessions held. Thirty-five residents participated in the first year. Resident perceived preparedness and confidence in taking call duties increased significantly following PREP. All residents rated PREP as extremely helpful or very helpful, the highest ratings possible. Overall, residents preferred active learning strategies. All qualitative data revealed positive effects of PREP. Clinical faculty in the pulmonology division found PREP similarly helpful and felt that PREP better prepared residents to provide care to pulmonary inpatients than our previous model. Discussion Our monthly preparatory boot camp on the first day of residents’ inpatient pulmonary rotation has improved resident experience, preparedness, and ability to care for complex pulmonary patients. The curriculum was adjusted in response to feedback to increase hands-on time and interactive sessions. Protected time for residents and active learning strategies were key to success of PREP.

The American Thoracic Society Core Curriculum updates clinicians annually in adult and pediatric pulmonary disease, medical critical care, and sleep medicine, in a 3- to 4-year recurring cycle of topics. These topics will be presented at the 2020 International Conference. Below is the pediatric pulmonary medicine core, including pediatric hypoxemic respiratory failure; modalities in noninvasive management of chronic respiratory failure in childhood; surgical and nonsurgical management of congenital lung malformations; an update on smoke inhalation lung injury; an update on vaporizers, e-cigarettes, and other electronic delivery systems; pulmonary complications of sarcoidosis; pulmonary complications of congenital heart disease; and updates on the management of congenital diaphragmatic hernia.

The effect of mechanical insufflation-exsufflation (MIE) for airway clearance in patients with spinal muscular atrophy type I (SMA-I) on the distribution of ventilation in the lung is unknown, as is the duration of its beneficial effects. A pilot study to investigate the feasibility of using three dimensional (3-D) electrical impedance tomography (EIT) images to estimate lung volumes pre- and post-MIE for assessing the effectiveness of mechanical insufflation-exsufflation (MIE) was conducted in 6 pediatric patients with SMA-I in the neuromuscular clinic at Children's Hospital Colorado. EIT data were collected before, during, and after the MIE procedure on two rows of 16 electrodes placed around the chest. Lung volumes were computed from the images and compared before, during, and after the MIE procedure to assess the ability of EIT to estimate changes in lung volume during insufflation and exsufflation. Images of pulsatile pulmonary perfusion were computed in subjects able to perform breath-holding. In four of the six subjects, lung volumes during tidal breathing increased after MIE (average change from pre to post MIE was 58.8±55.1 mL). The time-dependent plots of lung volume computed from the EIT data clearly show when the MIE device insufflates and exsufflates air and the rest periods between mechanical coughs. Images of pulmonary pulsatile perfusion were computed from data collected during breathing pauses. The results suggest that EIT holds promise for estimating lung volumes and ventilation/perfusion mismatch, both of which are useful for assessing the effectiveness of MIE in clearing mucus plugs.

Background Patients admitted to hospital for surgery are at an increased risk of venous thromboembolism. Pharmaco-thromboprophylaxis and mechanical prophylaxis (usually graduated compression stockings or intermittent pneumatic compression) have been shown to reduce the incidence of venous thromboembolism. The evidence base supporting the National Institute for Health and Care Excellence’s recommendation for the use of graduated compression stockings for venous thromboembolism prevention in the UK has recently been challenged. It is unclear if the risks and costs associated with graduated compression stockings are justified for deep-vein thrombosis prevention in moderate- and high-risk elective surgical inpatients receiving low-dose low-molecular-weight heparin pharmaco-thromboprophylaxis. Objectives The primary objective was to compare the venous thromboembolism rate in elective surgical inpatients at moderate or high risk of venous thromboembolism who were receiving either graduated compression stockings and low-dose low-molecular-weight heparin (standard care) or low-dose low-molecular-weight heparin alone (intervention). Design This was a pragmatic, multicentre, prospective, non-inferiority, randomised controlled trial. Setting This took place in secondary care NHS hospitals in the UK. Participants Patients aged ≥ 18 years who were assessed to be at moderate or high risk of venous thromboembolism according to the NHS England venous thromboembolism risk assessment tool (or the trust equivalent based on this form) and who were not contraindicated to low-molecular-weight heparin or graduated compression stockings were deemed eligible to take part. Interventions Participants were randomised 1 : 1 to either low-molecular-weight heparin or low-molecular-weight heparin and graduated compression stockings. Main outcome measures The primary outcome measure was venous thromboembolism up to 90 days after surgery. A combined end point of duplex ultrasound-proven new lower-limb deep-vein thrombosis (symptomatic or asymptomatic) plus imaging-confirmed symptomatic pulmonary embolism. Secondary outcomes included quality of life, compliance with graduated compression stockings and low-molecular-weight heparin during admission, and all-cause mortality. Results A total of 1905 participants were randomised and 1858 were included in the intention-to-treat analysis. A primary outcome event occurred in 16 out of 937 (1.7%) patients in the low-molecular-weight heparin-alone arm compared with 13 out of 921 (1.4%) patients in the low-molecular-weight heparin plus graduated compression stockings arm. The risk difference between low-molecular-weight heparin and low-molecular-weight heparin plus graduated compression stockings was 0.30% (95% confidence interval –0.65% to 1.26%). As the 95% confidence interval did not cross the non-inferiority margin of 3.5% (p Limitations In total, 13% of patients did not receive a duplex ultrasound scan that could have detected further asymptomatic deep-vein thrombosis. However, missing scans were balanced between both trial arms. The subpopulation of those aged ≥ 65 years assessed as being at a moderate risk of venous thromboembolism was under-represented in the study; however, this reflects that this group is under-represented in the general population. Conclusions For elective surgical patients at moderate or high risk of venous thromboembolism, administration of pharmaco-thromboprophylaxis alone is non-inferior to a combination of pharmaco-thromboprophylaxis and graduated compression stockings. These findings indicate that graduated compression stockings may be unnecessary for most elective surgical patients. Future work Further studies are required to evaluate whether or not adjuvant graduated compression stockings have a role in patients receiving extended thromboprophylaxis, beyond the period of hospital admission, following elective surgery or in patients undergoing emergency surgical procedures. Trial registration Current Controlled Trials ISRCTN13911492. Funding This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 69. See the NIHR Journals Library website for further project information.

We performed a point prevalence study on infants with severe BPD collecting data on type and settings of ventilatory support; 187 infants were included from 15 centers, 51% who were on invasive positive pressure ventilation. We found significant center-specific variation in ventilator modes.

Background Electroporated plasmid IL-12 (TAVO or tavokinogene telseplasmid) is a novel pro-inflammatory intratumoral therapy with substantial single agent activity in melanoma, which has been shown to synergize with anti-PD-1 antibodies in patients predicted as non-responders to anti-PD-1.1 2 Interim data from patients with stage III/IV melanoma actively progressing on anti-PD-1 antibody are presented herein. Methods Patients with confirmed disease progression by RECIST v1.1 after at least 12 weeks of treatment on pembrolizumab or nivolumab (or combination checkpoint blockade) and within 12 weeks of last dose (with no intervening therapies) were enrolled. There was no limit on the number of prior lines of therapy. At least one accessible lesion was electroporated with plasmid IL-12 (pIL-12-EP) on days 1, 5 and 8 every 6 weeks and pembrolizumab was administered every 3 weeks. Tumor response in treated and untreated lesions was assessed by RECIST v1.1 every 12 weeks. Endpoints include ORR, safety, PFS, OS, and DOR. Results The first 56 patients treated of 100 planned were included in this interim analysis. Of these, 84% had Stage IV disease, 30% had M1c or M1d disease, and 27% had prior exposure to ipilimumab. In 54 efficacy evaluable patients the investigator-assessed ORR was 30% (3 CR/13 PR), 5 patients had 100% reduction of target lesions. All responses have been confirmed, only two responding patient progressed while on study, 2 patients completed the study with ongoing responses (figures 1 and 2). In patients with M1c/M1d disease, the ORR was 35.2% (n=6/17). Tumor reduction was observed in untreated lesions in 12 of 12 patients who had unaccessible lesions or accessible untreated lesions. The median overall survival (mOS) and duration of response (mDOR) has not been reached, with a median follow-up time of 13 months. Grade 3 treatment-related adverse events (TRAEs) were seen in 5.4% of patients, and there were no grade 4/5 TRAEs. The rate of grade 3 treatment-emergent (TEAEs) regardless of cause was 23.2%. The median time for pIL-12-EP treatment was 10 minutes (range 2,46). Consistent with prior studies of single-agent pIL-12-EP, tumor IHC, and transcriptomic assessments revealed hallmarks of antigen-specific antitumor immunity in this study. Additional analyses including microbiome, TCR clonality, and peripheral blood biomarker assays will be presented. Conclusions In this rigorously defined PD-1 antibody refractory patient population, the addition of pIL-12-EP to PD-1 antibody therapy induced deep, durable, systemic response in local treated and distant visceral metastatic untreated lesions with nominal systemic toxicity. Trial Registration Trial Registration: NCT#03132675 Ethics Approval The study was approved by a central IRB and/or local institutional IRBs/Ethics Committees as required for each participating institution. Consent Written informed consent was obtained from the patients participating within the trial, the current abstract does not contain sensitive or identifiable information requiring an additional consent from patients. References Algazi A, Bhatia S, Agarwala S, et al. Intratumoral delivery of tavokinogene telseplasmid yields systemic immune responses in metastatic melanoma patients. Annals of Oncology 2019;31:532–540. Algazi A, Twitty C, Tsai K, et al. Phase II trial for IL-12 plasmid transfection and PD-1 blockade in immunologically quiescent melanoma. Clinical Cancer Research 2020;26:2827-2837.

Introduction Caring for technology-dependent children, such as those with tracheostomy and ventilator dependence, can be new and frightening for pediatric residents. Education about emergencies in this patient population is important because these children are at risk for in-hospital complications. Safe care of the tracheostomy-dependent child requires the ability to recognize common complications, such as tracheostomy tube obstruction or decannulation, and intervene appropriately by suctioning and/or replacing the tracheostomy tube. This simulation-based curriculum teaches learners to identify and practice the management of these tracheostomy tube complications through low-fidelity simulation exercises. Methods We created a simulation session with three cases reflecting in-hospital scenarios encountered by resident physicians caring for tracheostomy-dependent children in the inpatient setting. The simulation scenario, simulation environment preparation, materials list, and debriefing outline are provided for the instructor for each simulation case. Validity evidence for the assessment tool was obtained by calculating the interrater reliability of two different raters. Resident feedback was obtained through anonymous surveys. Results Twelve pediatric senior residents completed the experience. It received overwhelmingly positive feedback on learner evaluation forms, with 90% finding the experience very or extremely helpful. The intraclass correlation coefficient of interrater reliability for our assessment tool was 0.93. Discussion The simulation was well received by residents. The interrater reliability was acceptable. This low-fidelity simulation exercise can easily be executed with minimal materials or instructor training. High-yield, just-in-time training with postcase debriefing is key to the simulation's success.

BACKGROUND: Psoriasis is a chronic inflammatory disease affecting ~2-3% of the Australasian population. Therapeutic options include topical agents, phototherapy, systemic immunomodulators and biologic agents. Biologics present an acceptable short- and medium-term safety profile, derived mainly from randomised controlled trials (RCTs) and, however, may not represent real-world rates of adverse events (AEs). METHODS: A retrospective, observational study of patients enrolled in The Australasian Psoriasis Registry from April 2008 to October 2018 was conducted. Data were collected from 104 sites in Australia and New Zealand. Patient characteristics, treatments and AE data were collected. AEs were classified by MedDRA System events. RESULTS: 2094 patients were included (3765 patient-treatments), comprising; 1110 phototherapy, 1280 systemic and 1375 biologic therapy patient-treatments. Treatment arms were not mutually exclusive. The mean ± SD from date of diagnosis of psoriasis to commencement of biologic therapy was 8.9 ± 12.3 years. Methotrexate had the longest exposure time (3740.3 patient-years), and ustekinumab had the longest median (95% CI) time on treatment, 4.3 years (2.2, 6.6). AE differences on biologic treatment were present between patients who would have been eligible or ineligible for RCTs. Approximately 29% of registry patients would have been excluded from clinical trials enrolment. Patients ineligible for RCTs had increased adjusted hazard ratios (95% CI) of: infections and infestations (2.3, 1.7-3.1; P

Coronavirus disease 2019 (COVID-19) is forcing cardiology departments to rapidly adapt existing clinical guidelines to a new reality and this is especially the case for acute coronary syndrome pathways. In this focused review, the authors discuss how COVID-19 is affecting acute cardiology care and propose pragmatic guideline modifications for the diagnosis and management of acute coronary syndrome patients, particularly around the appropriateness of invasive strategies as well as length of hospital stay. The authors also discuss the use of personal protective equipment for healthcare workers in cardiology. Based on shared global experiences and growing peer-reviewed literature, it is possible to put in place modified acute coronary syndrome treatment pathways to offer safe pragmatic decisions to patients and staff.

ObjectivesTo investigate whether the use of graduated compression stockings (GCS) offers any adjuvant benefit when pharmaco-thromboprophylaxis is used for venous thromboembolism prophylaxis in patients undergoing elective surgery.DesignOpen, multicentre, randomised, controlled, non-inferiority trial.SettingSeven National Health Service tertiary hospitals in the United Kingdom.Participants1905 elective surgical inpatients (≥18 years) assessed as being at moderate or high risk of venous thromboembolism were eligible and consented to participate.InterventionParticipants were randomly assigned (1:1) to receive low molecular weight heparin (LMWH) pharmaco-thromboprophylaxis alone or LMWH pharmaco-thromboprophylaxis and GCS.Outcome measuresThe primary outcome was imaging confirmed lower limb deep vein thrombosis with or without symptoms, or pulmonary embolism with symptoms within 90 days of surgery. Secondary outcome measures were quality of life, compliance with stockings and LMWH, lower limb complications related to GCS, bleeding complications, adverse reactions to LMWH, and all cause mortality.ResultsBetween May 2016 and January 2019, 1905 participants were randomised. 1858 were included in the intention to treat analysis (17 were identified as ineligible after randomisation and 30 did not undergo surgery). A primary outcome event occurred in 16 of 937 (1.7%) patients in the LMWH alone group compared with 13 of 921 (1.4%) in the LMWH and GCS group. The risk difference between the two groups was 0.30% (95% confidence interval −0.65% to 1.26%). Because the 95% confidence interval did not cross the non-inferiority margin of 3.5% (PConclusionsFor patients who have elective surgery and are at moderate or high risk of venous thromboembolism, administration of pharmaco-thromboprophylaxis alone is non-inferior to a combination of pharmaco-thromboprophylaxis and GCS. These findings indicate that GCS might be unnecessary in most patients undergoing elective surgery.Trial registrationISRCTN13911492.

Chronic hand/foot eczemas are common, but treatment is often challenging, with widespread dissatisfaction over current available options. Detailed history is important, particularly with regard to potential exposure to irritants and allergens. Patch testing should be regarded as a standard investigation. Individual treatment outcomes and targets, including systemic therapy, should be discussed early with patients, restoring function being the primary goal, with clearing the skin a secondary outcome. Each new treatment, where appropriate, should be considered additive or overlapping to any previous therapy. Management extends beyond mere pharmacological or physical treatment, and requires an encompassing approach including removal or avoidance of causative factors, behavioural changes and social support. To date, there is little evidence to guide sequences or combinations of therapies. Moderately symptomatic patients (e.g. DLQI ≥ 10) should be started on a potent/super-potent topical corticosteroid applied once or twice per day for 4 weeks, with tapering to twice weekly application. If response is inadequate, consider phototherapy, and then a 12-week trial of a retinoid (alitretinoin or acitretin). Second line systemic treatments include methotrexate, ciclosporin and azathioprine. For patients presenting with severe symptomatic disease (DLQI ≥ 15), consider predniso(lo)ne 0.5-1.0 mg/kg/day (or ciclosporin 3 - 5 mg/kg/day) for 4-6 weeks with tapering, and then treating as for moderate disease as above. In non-responders, botulinum toxin and/or iontophoresis, if associated with hyperhidrosis, may sometimes help. Some patients only respond to long-term systemic corticosteroids. The data on sequencing of newer agents, such as dupilumab or JAK inhibitors, are immature.

Patients on immunomodulators, including biologic agents and new small molecular inhibitors, for cutaneous disease, represent a potentially vulnerable population during the COVID‐19 pandemic. There is currently insufficient evidence to determine whether patients on systemic immunomodulators are at increased risk of developing COVID‐19 disease or more likely to have severe disease. As such, clinicians need to assess the benefit‐to‐risk ratio on a case‐by‐case basis. In patients with suspected or confirmed COVID‐19 disease, all immunomodulators used for skin diseases should be immediately withheld, with the possible exception of systemic corticosteroid therapy, which needs to be weaned. In patients who develop symptoms or signs of an upper respiratory tract infection, but COVID‐19 is not yet confirmed, consider dose reduction or temporarily cessation for 1–2 weeks. In otherwise well patients, immunomodulators and biologics should be continued. In all patients, and their immediate close contacts, the importance of preventative measures to minimise human‐to‐human transmission cannot be overemphasised.

Coronavirus disease 2019 (COVID-19) is the disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), as named by the International Committee on Taxonomy of Viruses (ICTV). There is very limited evidence base to formulate specific advice for dermatology patients on immunomodulators with regards to COVID-19. The following is based on expert opinion, taking into account known risks of influenza (a negative sense single-stranded RNA virus) and other, positive-sense single-stranded, RNA virus infections (such as SARS, MERS, and the common cold). An Australia/New Zealand consensus document is in development.

Emergency department (ED) presentation with chest pain accounts for approximately 20% of acute hospital admissions, and delays in the investigation and management of these patients increase the pressure on emergency and medical departments. We implemented a pathway within our trust to improve the efficiency of acute chest pain management. This included the development of a chest pain management algorithm, a short-stay heart assessment centre and a policy to immediately transfer acute coronary syndrome patients to cardiology. The introduction of the chest pain pathway resulted in fewer admissions from the ED with chest pain (34.2% vs 19.0%; p

Ciclosporin (CsA) is a systemic immunosuppressive agent indicated for use in the treatment of patients with recalcitrant atopic dermatitis (AD). Studies demonstrate reasonable evidence of benefit compared with placebo. However as biologic agents are under development for use in AD, an assessment of the use, attitude to and safety of CsA is essential in understanding unmet needs in severe AD. We present the results of a survey asking questions relating to initial dose, duration of prescription, precautions and monitoring undertaken during treatment, adverse events seen, and hierarchy of use for systemic agents. This survey was distributed at the annual meeting of the Australasian College of Dermatologists. Twenty-two percent of respondents never prescribe CsA, and 50% prescribe it only 1-2 times per month. When prescribed, the most frequently recommended duration was 6-12 months (24%). Of prescribers, 56% start with a low dose of

Pulmonary vascular disease, in particular, pulmonary hypertension (PH), is quite prevalent in children with bronchopulmonary dysplasia (BPD). Recent clinical and preclinical advances in research related to this condition have led to an improved understanding of the pathophysiology of PH and the complex interactions between heart, lung, and pulmonary vasculature in infants with BPD. These findings can be translated into clinical care with targeted ventilatory strategies, improved awareness and aggressive management of cardiopulmonary insults, and the initiation of specific vasodilator therapy when appropriate. A multidisciplinary approach to treating PH in BPD can help reduce morbidity both in the neonatal intensive care unit and beyond.

Chronic total occlusions (CTO) are commonly encountered in patients undergoing coronary angiography; however, percutaneous coronary intervention (PCI) is infrequently performed owing to technical difficulty, the perceived risk of complications and a lack of randomized data. The aim of this study was to analyse the frequency and outcomes of CTO-PCI procedures in a large contemporary cohort of successive patients.We undertook an observational cohort study of 48 234 patients with stable angina of which 5496 (11.4%) procedures were performed for CTOs between 2005 and 2015 at nine tertiary cardiac centres across London, UK. Outcome was assessed by in-hospital major adverse cardiac events and all-cause mortality at a median follow-up of 4.8 years (interquartile range: 2.2-6.4 years).Over time, there was an increase in the proportion of elective PCI procedures performed for CTOs, but no increase in the absolute number. Overall success rates increased over time (74.3% in 2005 to 81.5% in 2015; P=0.0003) despite an increase in case complexity (previous myocardial infarction, diabetes, renal failure, previous coronary artery bypass grafting, peripheral vascular disease and left ventricular impairment) that correlated with procedural advancements. Successful CTO PCI was associated with lower mortality [9.5%, 95% confidence interval (CI): 8.1-11.6 vs. 15.3%, 95% CI: 13.7-20.6, P0.0001] that persisted after multivariate cox analysis (hazard ratio: 0.37, 95% CI: 0.25-0.62) and propensity matching (hazard ratio=0.36, 95% CI: 0.18-0.73, P=0.0005).Successful procedures were associated with lower mortality suggesting that the greater uptake of CTO PCI may improve clinical outcomes in a wider population than are currently being offered therapy.

The Australasian Psoriasis Collaboration has developed a clinical practice narrative with respect to the relationship between psoriasis, its treatment and infection. The cutaneous microbiome of patients with psoriasis is different to those without psoriasis, although the significance of this is unclear. Whilst a wide range of microorganisms has been associated with psoriasis (including β-haemolytic streptococci, Staphylococcus aureus, Porphyromonas gingivalis, Candida albicans, Chlamydia psittaci, human immunodeficiency virus and hepatitis C virus), there is limited evidence that antimicrobial therapy is of direct benefit in preventing flares of psoriasis. Psoriasis is independently associated with an increased risk of serious infection, but the absolute risk is low. The risk of serious infections is further increased with immune-modulatory treatments. The decision whether to, and when to, stop or resume immune-modulatory treatment after a serious infection has occurred depends on risk assessment for that patient, taking into account the infection being treated, the risk of recurrent infection, any interventions that can modify the risk and the need for psoriasis control. Live vaccines (e.g. MMR, varicella, zoster and yellow fever) are generally contraindicated in patients with psoriasis on immune-modulatory agents, but this depends on the degree of immune suppression and individual risk factors. Wound healing in psoriasis is normal. Treatment with infliximab, adalimumab, etanercept, methotrexate and ciclosporin can safely be continued through low-risk surgical procedures. For moderate- and high-risk surgeries, a case-by-case approach should be taken based on the patient's individual risk factors and comorbidities.

Modern conservation requires robust predictions about how management will affect an ecosystem and its species. The large uncertainties about the type and strength of interactions make model predictions particularly unreliable. In this paper, we show how fuzzy cognitive maps can produce robust predictions in complex and uncertain ecosystems. The use of fuzzy cognitive maps has been increasing markedly, but there are two critical issues with the approach: translation of expert knowledge into the FCM is often done incorrectly; and sensitivity analyses are rarely conducted. Translating expert knowledge is a constant challenge for ecological modellers, often because experts know about the behaviour of a system, but modellers need to know model parameters, which subsequently lead to system behaviour. We describe how to correctly incorporate expert knowledge into FCMs, and we describe how to appropriately conduct uncertainty and sensitivity analysis. We illustrate this process with a previously published network for feral cat and black rat control on Christmas Island. Perverse indirect effects of conservation management are a key concern, and methods to help us make informed decisions are required. Fuzzy cognitive maps are a promising approach for this, but it requires the methodological improvements that we present here.

A rare autosomal recessive disorder caused by mutations in the B3GALT6 gene on chromosome 1p36 results in deficiency of β-1,3-galactosyltransferase 6, an enzyme critical for glycosaminoglycan biosynthesis. Defects in this gene result in a phenotype that has features of both skeletal dysplasia and a connective tissue disorder. The anesthetic considerations for children with this disorder have not previously been described. We report a collaborative, multidisciplinary approach to the perioperative care of a child with B3GALT6 mutations with severe phenotypic expression.

Purpose With increasing frequency, speech-language pathologists are asked to provide feeding and swallowing evaluations and treatment to children with tracheostomies. The following article provides...

Most species are imperfectly detected during biological surveys, which creates uncertainty around their abundance or presence at a given location. Decision makers managing threatened or pest species are regularly faced with this uncertainty. Wildlife diseases can drive species to extinction; thus, managing species with disease is an important part of conservation. Devil facial tumor disease (DFTD) is one such disease that led to the listing of the Tasmanian devil (Sarcophilus harrisii) as endangered. Managers aim to maintain devils in the wild by establishing disease-free insurance populations at isolated sites. Often a resident DFTD-affected population must first be removed. In a successful collaboration between decision scientists and wildlife managers, we used an accessible population model to inform monitoring decisions and facilitate the establishment of an insurance population of devils on Forestier Peninsula. We used a Bayesian catch-effort model to estimate population size of a diseased population from removal and camera trap data. We also analyzed the costs and benefits of declaring the area disease-free prior to reintroduction and establishment of a healthy insurance population. After the monitoring session in May-June 2015, the probability that all devils had been successfully removed was close to 1, even when we accounted for a possible introduction of a devil to the site. Given this high probability and the baseline cost of declaring population absence prematurely, we found it was not cost-effective to carry out any additional monitoring before introducing the insurance population. Considering these results within the broader context of Tasmanian devil management, managers ultimately decided to implement an additional monitoring session before the introduction. This was a conservative decision that accounted for uncertainty in model estimates and for the broader nonmonetary costs of mistakenly declaring the area disease-free.

This case study intends to show how Internet of Things (IoT) technology can be used to tackle development challenges by using the case study of BBOXX- a Solar Home Systems provider operating in South-Western Kenya and across Rwanda, and its SMART Solar platform applied to nearly 20,000 currently active systems. It aims to highlight the benefits of such technology to its users and how it can be utilised to create scalable business models for energy access through improved customer understanding. However, it also shows the difficulties in designing, developing and deploying appropriate technologies in an affordable and impactful way. Similar applications in the water sector are briefly looked at to further explore the potential and the challenges of IoT technologies in driving social and economic development. The case study raises ethical questions about the storage, collection and sharing of data and explores whether the data protection models prevalent in the developed world are applicable in a development context. It offers ideas for future research and policy recommendations, pointing to the need of including financial, socio-economic and ethical considerations in the processes of innovative solutions development.

Invasive species threaten endangered species worldwide and substantial effort is focused on their control. Eradication projects require critical resource allocation decisions, as they affect both the likelihood of success and the overall cost. However, these complex decisions must often be made within data-poor environments. Here we develop a mathematical framework to assist in resource allocation for invasive species control projects and we apply it to the proposed eradication of the tropical fire ant (Solenopsis geminata) from the islands of Ashmore Reef in the Timor Sea. Our framework contains two models: a population model and a detection model. Our stochastic population model is used to predict ant abundance through time and allows us to estimate the probability of eradication. Using abundance predictions from the population model, we use the detection model to predict the probability of ant detection through time. These models inform key decisions throughout the project, which include deciding how many baiting events should take place, deciding whether to invest in detector dogs and setting surveillance effort to confirm eradication following control. We find that using a combination of insect growth regulator and toxins are required to achieve a high probability of eradication over 2 years, and we find that using two detector dogs may be more cost-effective than the use of lure deployment, provided that they are used across the life of the project. Our analysis lays a foundation for making decisions about control and detection throughout the project and provides specific advice about resource allocation.