Is there a benefit for anesthesiologists of adding difficult airway scenarios for learning fiberoptic intubation skills using virtual reality training? A randomized controlled study.

Fiberoptic intubation for a difficult airway requires significant experience. Traditionally only normal airways were available for high fidelity bronchoscopy simulators. It is not clear if training on difficult airways offers an advantage over training on normal airways. This study investigates the added value of difficult airway scenarios during virtual reality fiberoptic intubation training. A prospective multicentric randomized study was conducted 2019 to 2020, among 86 inexperienced anesthesia residents, fellows and staff. Two groups were compared: Group N (control, n = 43) first trained on a normal airway and Group D (n = 43) first trained on a normal, followed by three difficult airways. All were then tested by comparing their ORSIM® scores on 5 scenarios (1 normal and 4 difficult airways). The final evaluation ORSIM® score for the normal airway testing scenario was significantly higher for group N than group D: median score 76% (IQR 56.5-90) versus 58% (IQR 51.5-69, p = 0.0039), but there was no difference in ORSIM® scores for the difficult intubation testing scenarios. A single exposure to each of 3 different difficult airway scenarios did not lead to better fiberoptic intubation skills on previously unseen difficult airways, when compared to multiple exposures to a normal airway scenario. This finding may be due to the learning curve of approximately 5-10 exposures to a specific airway scenario required to reach proficiency.

Edge-Computing Video Analytics Solution for Automated Plastic-Bag Contamination Detection: A Case from Remondis.

The increased global waste generation rates over the last few decades have made the waste management task a significant problem. One of the potential approaches adopted globally is to recycle a significant portion of generated waste. However, the contamination of recyclable waste has been a major problem in this context and causes almost 75% of recyclable waste to be unusable. For sustainable development, efficient management and recycling of waste are of huge importance. To reduce the waste contamination rates, conventionally, a manual bin-tagging approach is adopted; however, this is inefficient and requires huge labor effort. Within household waste contamination, plastic bags have been found to be one of the main contaminants. Towards automating the process of plastic-bag contamination detection, this paper proposes an edge-computing video analytics solution using the latest Artificial Intelligence (AI), Artificial Intelligence of Things (AIoT) and computer vision technologies. The proposed system is based on the idea of capturing video of waste from the truck hopper, processing it using edge-computing hardware to detect plastic-bag contamination and storing the contamination-related information for further analysis. Faster R-CNN and You Only Look Once version 4 (YOLOv4) deep learning model variants are trained using the Remondis Contamination Dataset (RCD) developed from Remondis manual tagging historical records. The overall system was evaluated in terms of software and hardware performance using standard evaluation measures (i.e., training performance, testing performance, Frames Per Second (FPS), system usage, power consumption). From the detailed analysis, YOLOv4 with CSPDarkNet_tiny was identified as a suitable candidate with a Mean Average Precision (mAP) of 63% and FPS of 24.8 with NVIDIA Jetson TX2 hardware. The data collected from the deployment of edge-computing hardware on waste collection trucks was used to retrain the models and improved performance in terms of mAP, False Positives (FPs), False Negatives (FNs) and True Positives (TPs) was achieved for the retrained YOLOv4 with CSPDarkNet_tiny backbone model. A detailed cost analysis of the proposed system is also provided for stakeholders and policy makers.

Oligodendroglial macroautophagy is essential for myelin sheath turnover to prevent neurodegeneration and death.

Although macroautophagy deficits are implicated across adult-onset neurodegenerative diseases, we understand little about how the discrete, highly evolved cell types of the central nervous system use macroautophagy to maintain homeostasis. One such cell type is the oligodendrocyte, whose myelin sheaths are central for the reliable conduction of action potentials. Using an integrated approach of mouse genetics, live cell imaging, electron microscopy, and biochemistry, we show that mature oligodendrocytes require macroautophagy to degrade cell autonomously their myelin by consolidating cytosolic and transmembrane myelin proteins into an amphisome intermediate prior to degradation. We find that disruption of autophagic myelin turnover leads to changes in myelin sheath structure, ultimately impairing neural function and culminating in an adult-onset progressive motor decline, neurodegeneration, and death. Our model indicates that the continuous and cell-autonomous maintenance of the myelin sheath through macroautophagy is essential, shedding insight into how macroautophagy dysregulation might contribute to neurodegenerative disease pathophysiology.

Molecular epidemiology and antimicrobial resistance phenotype of paediatric bloodstream infections caused by Gram-negative bacteria.

Background: Gram-negative organisms are common causes of bloodstream infection (BSI) during the neonatal period and early childhood. Whilst several large studies have characterised these isolates in adults, equivalent data (particularly incorporating whole genome sequencing) is lacking in the paediatric population. Methods: We perform an epidemiological and sequencing based analysis of Gram-negative bloodstream infections (327 isolates (296 successfully sequenced) from 287 patients) in children <18 years old between 2008 and 2018 in Oxfordshire, UK. Results: Here we show that the burden of infection lies predominantly in neonates and that most infections are caused by Escherichia coli, Klebsiella spp. and Enterobacter hormaechei. There is no evidence in our setting that the proportion of antimicrobial resistant isolates is increasing in the paediatric population although we identify some evidence of sub-breakpoint increases in gentamicin resistance. The population structure of E. coli BSI isolates in neonates and children mirrors that in adults with a predominance of STs 131/95/73/69 and the same proportions of O-antigen serotypes. In most cases in our setting there is no evidence of transmission/point-source acquisition and we demonstrate the utility of whole genome sequencing to refute a previously suspected outbreak. Conclusions: Our findings support continued use of current empirical treatment guidelines and suggest that O-antigen targeted vaccines may have a role in reducing the incidence of neonatal sepsis.

Multihazards Scenario Generator: A Network-Based Simulation of Natural Disasters.

The impact of natural disasters has been increasing in recent years. Despite the developing international interest in multihazard events, few studies quantify the dynamic interactions that characterize these phenomena. It is argued that without considering the dynamic complexity of natural catastrophes, impact assessments will underestimate risk and misinform emergency management priorities. The ability to generate multihazard scenarios with impacts at a desired level is important for emergency planning and resilience assessment. This article demonstrates a framework for using graph theory and networks to generate and model the complex impacts of multihazard scenarios. First, the combination of maximal hazard footprints and exposed nodes (e.g., infrastructure) is used to create the hazard network. Iterative simulation of the network, defined by actual hazard magnitudes, is then used to provide the overall compounded impact from a sequence of hazards. Outputs of the method are used to study distributional ranges of multihazards impact. The 2016 Kaikoura earthquake is used as a calibrating event to demonstrate that the method can reproduce the same scale of impacts as a real event. The cascading hazards included numerous landslides, allowing us to show that the scenario set generated includes the actual impacts that occurred during the 2016 events.

CYK4 relaxes the bias in the off-axis motion by MKLP1 kinesin-6.

Centralspindlin, a complex of the MKLP1 kinesin-6 and CYK4 GAP subunits, plays key roles in metazoan cytokinesis. CYK4-binding to the long neck region of MKLP1 restricts the configuration of the two MKLP1 motor domains in the centralspindlin. However, it is unclear how the CYK4-binding modulates the interaction of MKLP1 with a microtubule. Here, we performed three-dimensional nanometry of a microbead coated with multiple MKLP1 molecules on a freely suspended microtubule. We found that beads driven by dimeric MKLP1 exhibited persistently left-handed helical trajectories around the microtubule axis, indicating torque generation. By contrast, centralspindlin, like monomeric MKLP1, showed similarly left-handed but less persistent helical movement with occasional rightward movements. Analysis of the fluctuating helical movement indicated that the MKLP1 stochastically makes off-axis motions biased towards the protofilament on the left. CYK4-binding to the neck domains in MKLP1 enables more flexible off-axis motion of centralspindlin, which would help to avoid obstacles along crowded spindle microtubules.

Canadian Urological Association guideline on male urethral stricture.

Urethral stricture is fundamentally a fibrosis of the urethral epithelial and associated corpus spongiosum, which in turn, causes obstruction of the urethral lumen. Patients with urethral stricture most commonly present with lower urinary tract symptoms, urinary retention or urinary tract infection but may also experience a broad spectrum of other signs and symptoms, including genitourinary pain, hematuria, abscess, ejaculatory dysfunction, or renal failure. When urethral stricture is initially suspected based on clinical assessment, cystoscopy is suggested as the modality that most accurately establishes the diagnosis. This recommendation is based on several factors, including the accuracy of cystoscopy, as well as its wide availability, lesser overall cost, and comfort of urologists with this technique. When recurrent urethral stricture is suspected, we suggest performing retrograde urethrography to further stage the length and location of the stricture or referring the patient to a physician with expertise in reconstructive urology. Ultimately, the treatment decision depends on several factors, including the type and acuity of patient symptoms, the presence of complications, prior interventions, and the overall impact of the urethral stricture on the patient's quality of life. Endoscopic treatment, either as dilation or internal urethrotomy, is suggested rather than urethroplasty for the initial treatment of urethral stricture. This recommendation applies to men with undifferentiated urethral stricture and does not apply to trauma-related urethral injuries, penile urethral strictures (hypospadias, lichen sclerosus), or suspected urethral malignancy. In the setting of recurrent urethral stricture, urethroplasty is suggested rather than repeat endoscopic management but this may vary depending on patient preference and impact of the symptoms on the patient.The purpose of this guideline is to provide a practical summary outlining the diagnosis and treatment of urethral stricture in the Canadian setting.

FHOD-1 is the only formin in Caenorhabditis elegans that promotes striated muscle growth and Z-line organization in a cell autonomous manner.

The striated body wall muscles of Caenorhabditis elegans are a simple model for sarcomere assembly. Previously, we observed deletion mutants for two formin genes, fhod-1 and cyk-1, develop thin muscles with abnormal dense bodies (the sarcomere Z-line analogs). However, this work left in question whether these formins work in a muscle cell autonomous manner, particularly since cyk-1(∆) deletion has pleiotropic effects on development. Using a fast acting temperature-sensitive cyk-1(ts) mutant, we show here that neither postembryonic loss nor acute loss of CYK-1 during embryonic sarcomerogenesis cause lasting muscle defects. Furthermore, mosaic expression of CYK-1 in cyk-1(∆) mutants is unable to rescue muscle defects in a cell autonomous manner, suggesting muscle phenotypes caused by cyk-1(∆) are likely indirect. Conversely, mosaic expression of FHOD-1 in fhod-1(Δ) mutants promotes muscle cell growth and proper dense body organization in a muscle cell autonomous manner. As we observe no effect of loss of any other formin on muscle development, we conclude FHOD-1 is the only worm formin that directly promotes striated muscle development, and the effects on formin loss in C. elegans are surprisingly modest compared to other systems.

The effects of personal protective equipment on airway management: An in-situ simulation.

The novel coronavirus disease (COVID-19) was declared a pandemic by the World Health Organisation on 11th March and has led to over 41,000 deaths in the UK. Public Health England guidance for aerosol generating procedures (AGP) requires the donning of personal protective equipment (PPE). We evaluated airway management skills using an in-situ emergency simulation. The scenarios were video recorded and scored by two independent assessors using a skill specific checklist. A total of 34 airway management procedures were evaluated. The checklist involved 13 steps with a maximum score of 26. The median (IQR [range]) checklist score was 25 (24-25 [20-26]). Four teams failed to intubate the trachea and proceeded to manage the airway using a supraglottic airway device. The mean (SD) intubation time was 47.9 (16.5) seconds and two anaesthetists (7%) required a second attempt. Our results show that airway management can be carried out successfully whilst donned in PPE. However, additional training in using newly introduced devices such as a McGrath® video laryngoscope is of paramount importance.

FLIRT: fast local infrared thermogenetics for subcellular control of protein function.

FLIRT (fast local infrared thermogenetics) is a microscopy-based technology to locally and reversibly manipulate protein function while simultaneously monitoring the effects in vivo. FLIRT locally inactivates fast-acting temperature-sensitive mutant proteins. We demonstrate that FLIRT can control temperature-sensitive proteins required for cell division, Delta-Notch cell fate signaling, and germline structure in Caenorhabditis elegans with cell-specific and even subcellular precision.

Trends over time in Escherichia coli bloodstream infections, urinary tract infections, and antibiotic susceptibilities in Oxfordshire, UK, 1998-2016: a study of electronic health records.

BACKGROUND: Escherichia coli bloodstream infections are increasing in the UK and internationally. The evidence base to guide interventions against this major public health concern is small. We aimed to investigate possible drivers of changes in the incidence of E coli bloodstream infection and antibiotic susceptibilities in Oxfordshire, UK, over the past two decades, while stratifying for time since hospital exposure. METHODS: In this observational study, we used all available data on E coli bloodstream infections and E coli urinary tract infections (UTIs) from one UK region (Oxfordshire) using anonymised linked microbiological data and hospital electronic health records from the Infections in Oxfordshire Research Database (IORD). We estimated the incidence of infections across a two decade period and the annual incidence rate ratio (aIRR) in 2016. We modelled the data using negative binomial regression on the basis of microbiological, clinical, and health-care-exposure risk factors. We investigated infection severity, 30-day all-cause mortality, and community and hospital amoxicillin plus clavulanic acid (co-amoxiclav) use to estimate changes in bacterial virulence and the effect of antimicrobial resistance on incidence. FINDINGS: From Jan 1, 1998, to Dec 31, 2016, 5706 E coli bloodstream infections occurred in 5215 patients, and 228 376 E coli UTIs occurred in 137 075 patients. 1365 (24%) E coli bloodstream infections were nosocomial (onset >48 h after hospital admission), 1132 (20%) were quasi-nosocomial (≤30 days after discharge), 1346 (24%) were quasi-community (31-365 days after discharge), and 1863 (33%) were community (>365 days after hospital discharge). The overall incidence increased year on year (aIRR 1·06, 95% CI 1·05-1·06). In 2016, 212 (41%) of 515 E coli bloodstream infections and 3921 (28%) of 13 792 E coli UTIs were co-amoxiclav resistant. Increases in E coli bloodstream infections were driven by increases in community (aIRR 1·10, 95% CI 1·07-1·13; p<0·0001) and quasi-community (aIRR 1·08, 1·07-1·10; p<0·0001) cases. 30-day mortality associated with E coli bloodstream infection decreased over time in the nosocomial (adjusted rate ratio [RR] 0·98, 95% CI 0·96-1·00; p=0·03) group, and remained stable in the quasi-nosocomial (adjusted RR 0·98, 0·95-1·00; p=0·06), quasi-community (adjusted RR 0·99, 0·96-1·01; p=0·32), and community (adjusted RR 0·99, 0·96-1·01; p=0·21) groups. Mortality was, however, substantial at 14-25% across all hospital-exposure groups. Co-amoxiclav-resistant E coli bloodstream infections increased in all groups across the study period (by 11-18% per year, significantly faster than co-amoxiclav-susceptible E coli bloodstream infections; pheterogeneity<0·0001), as did co-amoxiclav-resistant E coli UTIs (by 14-29% per year; pheterogeneity<0·0001). Previous year co-amoxiclav use in primary-care facilities was associated with increased subsequent year community co-amoxiclav-resistant E coli UTIs (p=0·003). INTERPRETATION: Increases in E coli bloodstream infections in Oxfordshire are primarily community associated, with substantial co-amoxiclav resistance; nevertheless, we found little or no change in mortality. Focusing interventions on primary care facilities, particularly those with high co-amoxiclav use, could be effective in reducing the incidence of co-amoxiclav-resistant E coli bloodstream infections, in this region and more generally. FUNDING: National Institute for Health Research.

Cell-intrinsic and -extrinsic mechanisms promote cell-type-specific cytokinetic diversity.

Cytokinesis, the physical division of one cell into two, is powered by constriction of an actomyosin contractile ring. It has long been assumed that all animal cells divide by a similar molecular mechanism, but growing evidence suggests that cytokinetic regulation in individual cell types has more variation than previously realized. In the four-cell Caenorhabditis elegans embryo, each blastomere has a distinct cell fate, specified by conserved pathways. Using fast-acting temperature-sensitive mutants and acute drug treatment, we identified cell-type-specific variation in the cytokinetic requirement for a robust forminCYK-1-dependent filamentous-actin (F-actin) cytoskeleton. In one cell (P2), this cytokinetic variation is cell-intrinsically regulated, whereas in another cell (EMS) this variation is cell-extrinsically regulated, dependent on both SrcSRC-1 signaling and direct contact with its neighbor cell, P2. Thus, both cell-intrinsic and -extrinsic mechanisms control cytokinetic variation in individual cell types and can protect against division failure when the contractile ring is weakened.

Use of a counterfactual approach to evaluate the effect of area closures on fishing location in a tropical tuna fishery.

Spatial closures are widely used in marine conservation and fisheries management and it is important to understand their contribution to achieving management objectives. Many previous evaluations of closed area effects have used before-after comparisons, which, without controlling for a full range of factors, cannot ascribe changes in fleet behaviour to area closures per se. In this study we used a counterfactual approach to disentangle the effect of two closed areas on fishing location from other competing effects on the behaviour of the Indian Ocean tuna purse seine fishery. Our results revealed an inconsistent effect of the one of the closed areas between years, after taking into account the influence of environmental conditions on fleet behaviour. This suggests that the policy of closing the area per se was not the main driver for the fleet allocating its effort elsewhere. We also showed a marked difference in effect between the two closed areas resulting from their different locations in the fishery area. These findings highlight the need to account for other key fleet behavioural drivers when predicting or evaluating the contribution of area closures to achieving conservation and fishery management objectives.

Low Efficiency Upconversion Nanoparticles for High-Resolution Coalignment of Near-Infrared and Visible Light Paths on a Light Microscope.

The combination of near-infrared (NIR) and visible wavelengths in light microscopy for biological studies is increasingly common. For example, many fields of biology are developing the use of NIR for optogenetics, in which an NIR laser induces a change in gene expression and/or protein function. One major technical barrier in working with both NIR and visible light on an optical microscope is obtaining their precise coalignment at the imaging plane position. Photon upconverting particles (UCPs) can bridge this gap as they are excited by NIR light but emit in the visible range via an anti-Stokes luminescence mechanism. Here, two different UCPs have been identified, high-efficiency micro540-UCPs and lower efficiency nano545-UCPs, that respond to NIR light and emit visible light with high photostability even at very high NIR power densities (>25 000 Suns). Both of these UCPs can be rapidly and reversibly excited by visible and NIR light and emit light at visible wavelengths detectable with standard emission settings used for Green Fluorescent Protein (GFP), a commonly used genetically encoded fluorophore. However, the high efficiency micro540-UCPs were suboptimal for NIR and visible light coalignment, due to their larger size and spatial broadening from particle-to-particle energy transfer consistent with a long-lived excited state and saturated power dependence. In contrast, the lower efficiency nano-UCPs were superior for precise coalignment of the NIR beam with the visible light path (∼2 µm versus ∼8 µm beam broadening, respectively) consistent with limited particle-to-particle energy transfer, superlinear power dependence for emission, and much smaller particle size. Furthermore, the nano-UCPs were superior to a traditional two-camera method for NIR and visible light path alignment in an in vivo Infrared-Laser-Evoked Gene Operator (IR-LEGO) optogenetics assay in the budding yeast Saccharomyces cerevisiae. In summary, nano-UCPs are powerful new tools for coaligning NIR and visible light paths on a light microscope.

The ecological connectivity of whale shark aggregations in the Indian Ocean: a photo-identification approach.

Genetic and modelling studies suggest that seasonal aggregations of whale sharks (Rhincodon typus) at coastal sites in the tropics may be linked by migration. Here, we used photo-identification (photo-ID) data collected by both citizen scientists and researchers to assess the connectedness of five whale shark aggregation sites across the entire Indian Ocean at timescales of up to a decade. We used the semi-automated program I3S (Individual Interactive Identification System) to compare photographs of the unique natural marking patterns of individual whale sharks collected from aggregations at Mozambique, the Seychelles, the Maldives, Christmas Island (Australia) and Ningaloo Reef (Australia). From a total of 6519 photos, we found no evidence of connectivity of whale shark aggregations at ocean-basin scales within the time frame of the study and evidence for only limited connectivity at regional (hundreds to thousands of kilometres) scales. A male whale shark photographed in January 2010 at Mozambique was resighted eight months later in the Seychelles and was the only one of 1724 individuals in the database to be photographed at more than one site. On average, 35% of individuals were resighted at the same site in more than one year. A Monte Carlo simulation study showed that the power of this photo-ID approach to document patterns of emigration and immigration was strongly dependent on both the number of individuals identified in aggregations and the size of resident populations.