Use of multiple pharmacodynamic measures to deconstruct the Nix-TB regimen in a short-course murine model of tuberculosis.

A major challenge for tuberculosis (TB) drug development is to prioritize promising combination regimens from a large and growing number of possibilities. This includes demonstrating individual drug contributions to the activity of higher-order combinations. A BALB/c mouse TB infection model was used to evaluate the contributions of each drug and pairwise combination in the clinically relevant Nix-TB regimen [bedaquiline-pretomanid-linezolid (BPaL)] during the first 3 weeks of treatment at human equivalent doses. The rRNA synthesis (RS) ratio, an exploratory pharmacodynamic (PD) marker of ongoing Mycobacterium tuberculosis rRNA synthesis, together with solid culture CFU counts and liquid culture time to positivity (TTP) were used as PD markers of treatment response in lung tissue; and their time-course profiles were mathematically modeled using rate equations with pharmacologically interpretable parameters. Antimicrobial interactions were quantified using Bliss independence and Isserlis formulas. Subadditive (or antagonistic) and additive effects on bacillary load, assessed by CFU and TTP, were found for bedaquiline-pretomanid and linezolid-containing pairs, respectively. In contrast, subadditive and additive effects on rRNA synthesis were found for pretomanid-linezolid and bedaquiline-containing pairs, respectively. Additionally, accurate predictions of the response to BPaL for all three PD markers were made using only the single-drug and pairwise effects together with an assumption of negligible three-way drug interactions. The results represent an experimental and PD modeling approach aimed at reducing combinatorial complexity and improving the cost-effectiveness of in vivo systems for preclinical TB regimen development.

A quantitative evaluation of aerosol generation during cardiopulmonary resuscitation.

It is unclear if cardiopulmonary resuscitation is an aerosol-generating procedure and whether this poses a risk of airborne disease transmission to healthcare workers and bystanders. Use of airborne transmission precautions during cardiopulmonary resuscitation may confer rescuer protection but risks patient harm due to delays in commencing treatment. To quantify the risk of respiratory aerosol generation during cardiopulmonary resuscitation in humans, we conducted an aerosol monitoring study during out-of-hospital cardiac arrests. Exhaled aerosol was recorded using an optical particle sizer spectrometer connected to the breathing system. Aerosol produced during resuscitation was compared with that produced by control participants under general anaesthesia ventilated with an equivalent respiratory pattern to cardiopulmonary resuscitation. A porcine cardiac arrest model was used to determine the independent contributions of ventilatory breaths, chest compressions and external cardiac defibrillation to aerosol generation. Time-series analysis of participants with cardiac arrest (n = 18) demonstrated a repeating waveform of respiratory aerosol that mapped to specific components of resuscitation. Very high peak aerosol concentrations were generated during ventilation of participants with cardiac arrest with median (IQR [range]) 17,926 (5546-59,209 [1523-242,648]) particles.l-1 , which were 24-fold greater than in control participants under general anaesthesia (744 (309-2106 [23-9099]) particles.l-1 , p < 0.001, n = 16). A substantial rise in aerosol also occurred with cardiac defibrillation and chest compressions. In a complimentary porcine model of cardiac arrest, aerosol recordings showed a strikingly similar profile to the human data. Time-averaged aerosol concentrations during ventilation were approximately 270-fold higher than before cardiac arrest (19,410 (2307-41,017 [104-136,025]) vs. 72 (41-136 [23-268]) particles.l-1 , p = 0.008). The porcine model also confirmed that both defibrillation and chest compressions generate high concentrations of aerosol independent of, but synergistic with, ventilation. In conclusion, multiple components of cardiopulmonary resuscitation generate high concentrations of respiratory aerosol. We recommend that airborne transmission precautions are warranted in the setting of high-risk pathogens, until the airway is secured with an airway device and breathing system with a filter.

The effect of branded versus standardized e-cigarette packaging and device designs: an experimental study of youth interest in vaping products.

OBJECTIVES: Standardized ('plain') packaging is effective in reducing the appeal of cigarettes among young people. This study examined the impact of plain packaging and brand imagery on interest in trying e-cigarettes among youth. STUDY DESIGN: Experimental design. METHODS: Two online experiments were conducted in February 2020 as part of the ITC Youth Tobacco & Vaping Survey, conducted with 13,624 16- to 19-year-olds in Canada, England, and the USA. In the between-group Experiment 1, participants were randomized to view a set of 3 e-cigarette brands, in either their original external packaging ('branded' condition) or standardized olive-green packaging ('standardized' condition), and asked to select the product they would be most interested in trying. The within-group Experiment 2 examined brand imagery directly on devices, including potential differences in appeal among subgroups. Each participant viewed 4 pod-style e-cigarette devices: one 'plain' and 3 in colourful 'skins'. Logistic regression models were conducted to test the effect of condition, adjusting for demographics, smoking and vaping status. RESULTS: In Experiment 1, participants in the 'standardized' packaging condition were significantly more likely to indicate 'I have no interest in trying any of these products' (72.3%) than those in the 'branded' condition (66.9%, AOR 1.45, 95% CI 1.33-1.59). Experiment 2 results indicated differences in e-cigarette appeal by sex in the selection of male- and female-oriented designs, and by cannabis use for a Rastafarian-themed design. CONCLUSIONS: Brand imagery on e-cigarettes can target products to specific subgroups. Removal of imagery, in the form of standardized packaging, has the potential to reduce interest in trying e-cigarettes among young people.

A quantitative evaluation of aerosol generation during awake tracheal intubation.

Aerosol-generating procedures are medical interventions considered high risk for transmission of airborne pathogens. Tracheal intubation of anaesthetised patients is not high risk for aerosol generation; however, patients often perform respiratory manoeuvres during awake tracheal intubation which may generate aerosol. To assess the risk, we undertook aerosol monitoring during a series of awake tracheal intubations and nasendoscopies in healthy participants. Sampling was undertaken within an ultraclean operating theatre. Procedures were performed and received by 12 anaesthetic trainees. The upper airway was topically anaesthetised with lidocaine and participants were not sedated. An optical particle sizer continuously sampled aerosol. Passage of the bronchoscope through the vocal cords generated similar peak median (IQR [range]) aerosol concentrations to coughing, 1020 (645-1245 [120-48,948]) vs. 1460 (390-2506 [40-12,280]) particles.l-1 respectively, p = 0.266. Coughs evoked when lidocaine was sprayed on the vocal cords generated 91,700 (41,907-166,774 [390-557,817]) particles.l-1 which was significantly greater than volitional coughs (p < 0.001). For 38 nasendoscopies in 12 participants, the aerosol concentrations were relatively low, 180 (120-525 [0-9552]) particles.l-1 , however, five nasendoscopies generated peak aerosol concentrations greater than a volitional cough. Awake tracheal intubation and nasendoscopy can generate high concentrations of respiratory aerosol. Specific risks are associated with lidocaine spray of the larynx, instrumentation of the vocal cords, procedural coughing and deep breaths. Given the proximity of practitioners to patient-generated aerosol, airborne infection control precautions are appropriate when undertaking awake upper airway endoscopy (including awake tracheal intubation, nasendoscopy and bronchoscopy) if respirable pathogens cannot be confidently excluded.

A computational account of item-based directed forgetting for nonwords: Incorporating orthographic representations in MINERVA 2.

Recent research on item-method directed forgetting demonstrates that forget instructions not only decrease recognition for targets, but also decrease false recognition for foils from the same semantic categories as targets instructed to be forgotten. According to the selective rehearsal account of directed forgetting, this finding suggests that remember instructions may engage elaborative rehearsal of the category-level information of items. In contrast to this explanation, Reid and Jamieson (Canadian Journal of Experimental Psychology / Revue canadienne de psychologie expérimentale, 76(2), 75-86, 2022) proposed that the differential rates of false recognition may emerge at retrieval when foils from "remember" and "forget" categories are compared to traces in memory. Using MINERVA S, an instance model of memory based on MINERVA 2 that incorporates structured semantic representations, Reid and Jamieson successfully simulated lower false recognition for foils from "forget" categories without assuming rehearsal of category-level information. In this study, we extend the directed forgetting paradigm to categories consisting of orthographically related nonwords. Presumably participants would have difficulty rehearsing category-level information for these items because they would have no pre-experimental knowledge of these categories. To simulate the findings in MINERVA S, we imported structured orthographic representations rather than semantic representations. The model not only predicted differential rates of false recognition for foils from "remember" and "forget" categories, but also predicted higher rates of false recognition overall than what was observed for semantic categories. The empirical data closely matched these predictions. These data suggest that differential rates of false recognition due to remember and forget instructions emerge at retrieval when participants compare recognition probes to traces stored in memory.

Accurate Measurement of the Optical Properties of Single Aerosol Particles Using Cavity Ring-Down Spectroscopy.

New approaches for the sensitive and accurate quantification of aerosol optical properties are needed to improve the current understanding of the unique physical chemistry of airborne particles and to explore their roles in fields as diverse as chemical manufacturing, healthcare, and atmospheric science. We have pioneered the use of cavity ring-down spectroscopy (CRDS), with concurrent angularly resolved elastic light scattering measurements, to interrogate the optical properties of single aerosol particles levitated in optical and electrodynamic traps. This approach enables the robust quantification of optical properties such as extinction cross sections for individual particles of known size. Our measurements can now distinguish the scattering and absorption contributions to the overall light extinction, from which the real and imaginary components of the complex refractive indices can be retrieved and linked to chemical composition. In this Feature Article, we show that this innovative measurement platform enables accurate and precise optical measurements for spherical and nonspherical particles, whether nonabsorbing or absorbing at the CRDS probe wavelength. We discuss the current limitations of our approach and the key challenges in physical and atmospheric chemistry that can now be addressed by CRDS measurements for single aerosol particles levitated in controlled environments.

Magseed localisation of non-palpable breast lesions: experience from a single centre.

AIM: To prospectively analyse patients undergoing magnetic seed (Magseed) localisation (MSL) to evaluate the outcome, and to retrospectively compare re-excision rates for MSL with previous wire-guided localisation (WGL) to assess the hypothesis that the introduction of MSL may lead to a lower re-excision rate. MATERIALS AND METHODS: MSL commenced at University Hospital Crosshouse in December 2017. No other changes were made to radiological or surgical practice during this time. Data were collected prospectively on all patients undergoing MSL between December 2017 and December 2019, in a single breast unit. Data were gathered retrospectively on patients who had undergone localised breast procedures between January 2016 and December 2019 for comparison of re-excision rates. RESULTS: Two hundred and fifty-five patients underwent MSL surgery between December 2017 and December 2019. Of those, 98% (n=250) patients underwent successful MSL at the first attempt. The Magseed was identified intraoperatively in 100% patients and surgical excision was performed. The re-excision rate reduced from 18.9% in 2016/2017, to 11.6% in 2018/2019 (p=0.098). CONCLUSION: In conclusion, Magseed localisation has proved to be a safe and effective way of localising breast lesions, with the advantage of high accuracy. The reduction in re-excision rates at University Hospital Crosshouse with the introduction of Magseed® localisation is a potential benefit, which requires further study.

Optimizing first line treatments for adults with OCD.

OCD is characterized by obsessions (recurrent, intrusive, unwanted thoughts, images or impulses and compulsions (repetitive behaviors or mental acts that the individual feels compelled to perform), which can manifest together or separately (Fineberg et al., 2020). NICE guidelines suggest that low intensity psychological treatments (including ERP) is the first line treatment for OCD, and that a "stepped care" treatment approach for OCD reserves combination treatment for adults with OCD with severe functional impairment, and for adults without an adequate response to: 1) treatment with an SSRI alone (12 weeks duration) or 2) CBT (including ERP) alone (NICE, 2005). Existing US treatment guidelines (APA guidelines) suggest that there are three first-line treatments for OCD (SSRI, CBT, SSRI+CBT) and recommends combined treatment for patients with an unsatisfactory response to monotherapy or for patients with severe OCD. Although, systematic review and meta-analysis of studies published in 1993-2014 suggest that combination treatment was not significantly better than CBT plus placebo (Ost et al., 2015), based on data from a recent systematic and meta-analysis which searched the two controlled trials registers maintained by the Cochrane Collaboration Common Mental Disorders group, the combination treatment approach is likely to be more effective than psychotherapeutic interventions alone, at least in severe obsessive-compulsive disorder (Skapinakis et al., 2016a). Based on data from Optimal treatment for OCD study conducted by Fineberg et al., (2018) combined treatment appeared to be the most effective especially when compared to CBT monotherapy, but SSRI monotherapy was found as the most cost effective. In this review we summarize available treatment recommendations.

Quantitative evaluation of aerosol generation during manual facemask ventilation.

Manual facemask ventilation, a core component of elective and emergency airway management, is classified as an aerosol-generating procedure. This designation is based on one epidemiological study suggesting an association between facemask ventilation and transmission during the SARS-CoV-1 outbreak in 2003. There is no direct evidence to indicate whether facemask ventilation is a high-risk procedure for aerosol generation. We conducted aerosol monitoring during routine facemask ventilation and facemask ventilation with an intentionally generated leak in anaesthetised patients. Recordings were made in ultraclean operating theatres and compared against the aerosol generated by tidal breathing and cough manoeuvres. Respiratory aerosol from tidal breathing in 11 patients was reliably detected above the very low background particle concentrations with median [IQR (range)] particle counts of 191 (77-486 [4-1313]) and 2 (1-5 [0-13]) particles.l-1 , respectively, p = 0.002. The median (IQR [range]) aerosol concentration detected during facemask ventilation without a leak (3 (0-9 [0-43]) particles.l-1 ) and with an intentional leak (11 (7-26 [1-62]) particles.l-1 ) was 64-fold (p = 0.001) and 17-fold (p = 0.002) lower than that of tidal breathing, respectively. Median (IQR [range]) peak particle concentration during facemask ventilation both without a leak (60 (0-60 [0-120]) particles.l-1 ) and with a leak (120 (60-180 [60-480]) particles.l-1 ) were 20-fold (p = 0.002) and 10-fold (0.001) lower than a cough (1260 (800-3242 [100-3682]) particles.l-1 ), respectively. This study demonstrates that facemask ventilation, even when performed with an intentional leak, does not generate high levels of bioaerosol. On the basis of this evidence, we argue facemask ventilation should not be considered an aerosol-generating procedure.

Conceptual metaphors influence memory automatically: Evidence from a divided attention false memory task.

Previous research has found that reading a list of ostensibly unrelated expressions based on the same underlying conceptual metaphor can evoke false recognition on a memory task for new expressions that use the same metaphor, the so-called conceptual metaphor false memory effect. We examined the automaticity of this effect by dividing participants' attention with a concurrent task. In Study 1, attention was manipulated while participants read the lists of expressions, whereas in Study 2, attention was manipulated both when they read the lists and when they were engaged in the later recognition memory test. Across both studies, the conceptual metaphor false memory effect was observed when conscious processing was limited by dividing attention. These data support the argument that conceptual metaphors are automatically activated when metaphorical expressions are read.

Hospitalization for computer-assisted hexapod ring fixation application - analyses of patient variability, peri-operative complications, hospital costs, and discharge status.

BACKGROUND: Computer-assisted hexapod ring fixation systems (HRF) are used for multiple conditions and in very diverse patient populations. This study analyzes perioperative outcomes following HRF application based on patient etiology and clinical presentation. METHODS: Data from patients in the Premier Hospital Billing Database between 2007-2019 undergoing HRF application were analyzed for the duration of patients' hospitalizations. Patients were grouped based on etiology: acquired deformity, arthrosis, congenital deformity, deep infection, infected nonunion, fracture, nonunion, and other post-operative complications. Demographics, comorbidities, operating room time (ORT), length of stay (LOS), peri-operative complications, and hospital costs were estimated using generalized linear models. Logistic regression evaluated factors associated with peri-operative complications. RESULTS: One thousand eight hundred eighteen patients (average age: 46.9, standard deviation (SD) (19.6) - 38.9% female) were included in the study, and included 72% fracture cases, 9.6% deep infection, 10.2% deformity (acquired: 5.9%, congenital: 4.3%), 4.2% nonunions, 2% arthrosis and 1.4% other sequelas from prior fractures. Comorbidities varied across diagnosis categories and age, 40% adults and 86% pediatric had no comorbidities. Pediatric cases mostly suffered from obesity (16.1%) and pulmonary disease (10.7%). Complicated diabetes was present in 45.9% of arthropathy and 34.3% of deep infection patients. ORT, LOS and inflation-adjusted hospital costs for all patients averaged 277.7 min (95% Confidence interval (CI): 265.1-290.3), 7.07 days (95% CI: 6.6-7.5) and $41,507 (95%CI: $39,728-$43,285), respectively, but were highest in patients with deep infection (ORT: 369 min (95%CI: $321.0-$433.8); LOS: 14.4 days (95%CI: $13.7-$15.1); Cost: $54,666 (95%CI: $47,960-$63,553)). The probability of having an intraoperative complication averaged 35% (95%CI: 28%-43%) in adult patients with deep infection vs 7% (95%CI: 2%-20%) in pediatric cases treated for congenital deformity. The risk for intraoperative complications was mostly associated with preexisting comorbidities, an Elixhauser > 5 was the most predictive risk factor for complications (odds ratios: 4.53 (95%CI: 1.71-12.00, p = 0.002). CONCLUSIONS: There is important heterogeneity among HRF patients. Adults with HRF for fracture, deep infection and arthrosis are at far greater risk for peri-operative complications vs. patients with deformity, especially pediatric deformity cases, mostly due to existing comorbidities and age. Device-specific HRF clinical studies cannot be generalized beyond their exact patient population.

Two-year clinical and economic burden, risk and outcomes following application of software-assisted hexapod ring fixation systems.

BACKGROUND: Multiplanar external fixation systems that employ software-assisted deformity correction consist of rings connected by angled struts, defined as hexapod ring fixators (HRF). Costs and outcomes associated with the application of HRFs are not well documented. This study was designed to provide a nationwide baseline understanding of the clinical presentation, risks, outcomes and payer costs, and healthcare resource utilization (HCU) of patients requiring application of an HRF, from the day of, and up to 2 years, post-application. METHODS: Patients with HRF application ("index") between 2007 and 2019 within the IBM Marketscan® Commercial Claims database were identified and categorized based on diagnosis: acquired deformity, arthropathy, congenital deformity, deep infection, nonunion, fracture, and other post-operative fracture sequelae. Demographics, comorbidities at index, complications post-index, HCU, and payments were analyzed. Payments were estimated using a generalized linear model and were adjusted for inflation to the 2020 consumer price index. Rates of deep infection and amputation were estimated up to 2 years post-index using Poisson regressions, and risk factors for each were estimated using logistic regression models. RESULTS: Six hundred ninety-five patients were included in our study (including 219 fractures, 168 congenital deformities, 68 deep infections, 103 acquired deformities). Comorbidities at index were significantly different across groups: less than 2% pediatrics vs 18% adults had 3 or more comorbidities, < 1% pediatric vs 29% adults had diabetes. Index payments ranged from $39,250-$75,350, with 12-months post-index payments ranging from $14,350 to $43,108. The duration of the HRF application ranged from 96 days to 174 days. Amputation was observed in patients with deep infection (8.9, 95% confidence interval (CI): 3.2-23.9%), nonunion (5.0, 95%CI: 1.6-15.4%) or fracture (2.7, 95%CI: 0.9-7.6%) at index. Complicated diabetes was the main predictor for deep infection (odds ratio (OR): 5.14, 95%CI: 2.50-10.54) and amputation (OR: 5.26, 95%CI: 1.79-15.51). CONCLUSIONS: Findings from this longitudinal analysis demonstrate the significant heterogeneity in patients treated with HRF, and the wide range in treatment intensity, payments, and outcomes. Risks for deep infection and amputation were primarily linked to the presence of complicated diabetes at the time of HRF application, suggesting a need for careful management of comorbid chronic conditions in patients requiring HRF for orthopedic care.

The RK processor: A program for analysing metaphor and word feature-listing data.

Feature-listing tasks are an invaluable resource for exploring how words, categories, and metaphors are represented. However, manually coding the generated features is time-consuming and expensive, and involves subjective judgments from the experimenter. The purpose of this paper is to introduce the "RK processor", a program that was developed in our lab to analyse metaphor feature data but which can also be applied to other feature-listing data. After detailing the steps of processing, we demonstrate that the processed feature data align with previous findings in which metaphor features were processed manually and that the processed features predict dimensions of metaphor judgments pertaining to comprehensibility and metaphor goodness. Lastly, we present several other applications for research on word similarity, compound words, categories and concepts, semantic ambiguity, incongruity resolution and computational modelling. The RK processor offers researchers a valuable tool to save time and resources and to maintain consistency in processing.

Mirror Generalization During Early Word Recognition.

The "recycling hypothesis" posits that the word recognition system is built upon minimal modifications to the neural architecture used in object recognition. In two masked priming lexical decision studies, we examined whether "mirror generalization," a phenomenon in object recognition, occurs in word recognition. In Study 1, we found that mirrored repetition and mirrored transposed letter primes elicited significant and equivalent priming effects for mirrored targets. In Study 2, we found that mirrored and non-mirrored repetition primes both significantly facilitated processing of mirrored targets, but the priming effect was much larger for non-mirrored primes. In both studies, we also found evidence of gender differences as females showed faster response times and a larger mirror priming effect compared to males. Taken together, we conclude that mirror generalization occurs in the early orthographic stage of word recognition, but not in the later stage of lexical access, and there is a gender difference when reading mirror words.

Coaching to enhance qualified surgeons' non-technical skills: a systematic review.

INTRODUCTION: The lack of an effective continuing professional development programme for qualified surgeons, specifically one that enhances non-technical skills (NTS), is an issue receiving increased attention. Peer-based coaching, used in multiple professions, is a proposed method to deliver this. The aim of this study was to undertake a systematic review of the literature to summarize the quantity and quality of studies involving surgical coaching of NTS in qualified surgeons. METHODS: A systematic search of the literature was performed through MEDLINE, EMBASE, Cochrane Collaboration and PsychINFO. Studies were selected based on predefined inclusion and exclusion criteria. Data for the included studies was independently extracted by two reviewers and the quality of the studies evaluated using the Medical Education and Research Study Quality Instrument (MERSQI). RESULTS: Some 4319 articles were screened from which 19 met the inclusion criteria. Ten studies involved coaching of individual surgeons and nine looked at group coaching of surgeons as part of a team. Group coaching studies used non-surgeons as coaches, included objective assessment of NTS, and were of a higher quality (average MERSQI 13.58). Individual coaching studies focused on learner perception, used experienced surgeons as coaches and were of a lower quality (average MERSQI 11.58). Individual coaching did not show an objective improvement in NTS for qualified surgeons in any study. CONCLUSION: Surgical coaching of qualified surgeons' NTS in a group setting was found to be effective. Coaching of individual surgeons revealed an overall positive learner perception but did not show an objective improvement in NTS for qualified surgeons.

Can Multi-threaded Flux Tubes in Coronal Arcades Support a Magnetohydrodynamic Avalanche?

Magnetohydrodynamic (MHD) instabilities allow energy to be released from stressed magnetic fields, commonly modelled in cylindrical flux tubes linking parallel planes, but, more recently, also in curved arcades containing flux tubes with both footpoints in the same photospheric plane. Uncurved cylindrical flux tubes containing multiple individual threads have been shown to be capable of sustaining an MHD avalanche, whereby a single unstable thread can destabilise many. We examine the properties of multi-threaded coronal loops, wherein each thread is created by photospheric driving in a realistic, curved coronal arcade structure (with both footpoints of each thread in the same plane). We use three-dimensional MHD simulations to study the evolution of single- and multi-threaded coronal loops, which become unstable and reconnect, while varying the driving velocity of individual threads. Experiments containing a single thread destabilise in a manner indicative of an ideal MHD instability and consistent with previous examples in the literature. The introduction of additional threads modifies this picture, with aspects of the model geometry and relative driving speeds of individual threads affecting the ability of any thread to destabilise others. In both single- and multi-threaded cases, continuous driving of the remnants of disrupted threads produces secondary, aperiodic bursts of energetic release.

High time resolution measurements of droplet evaporation kinetics and particle crystallisation.

A refined technique for observing the complete evaporation behaviour of free-falling droplets, from droplet generation to complete solvent evaporation, with ultra-high time resolution is introduced and benchmarked. High-resolution phase-delay stroboscopic imaging is employed to simultaneously resolve the evolving droplet morphology, geometric and aerodynamic diameters, throughout the evaporative lifetime with a user-controlled < µs timescale. This allows rapid, complex morphological changes, such as crystallisation events, to be clearly observed and the corresponding mechanisms to be inferred. The dried particles are sampled for offline SEM analysis and the observed morphologies compared to the inflight imaging. Density changes can be calculated directly from the deviation between the geometric and aerodynamic diameters. The full capabilities of the new technique are demonstrated by examination of the different evaporation behaviours and crystallisation mechanisms for aqueous sodium chloride droplets evaporating under different ambient relative humidity (RH) conditions. The crystallisation window, defined as the time taken from initial to complete crystallisation, is shown to be RH dependent, extending from 0.03 s at 20% RH and 0.13 s at 40% RH. The different crystallisation mechanisms observed during the experiments are also clearly reflected in the final structure of the dry particles, with multi-crystal structures produced at low RH compared to single-crystal structures at higher RH. It is anticipated that this technique will unlock measurements which explore the evaporation behaviour and crystallisation mechanisms for rapid, complex droplet drying events, and with increasingly non-ideal solutions, relevant to industrial applications.

Finite Element Analysis of Fracture Fixation.

PURPOSE OF REVIEW: Fracture fixation aims to provide stability and promote healing, but remains challenging in unstable and osteoporotic fractures with increased risk of construct failure and nonunion. The first part of this article reviews the clinical motivation behind finite element analysis of fracture fixation, its strengths and weaknesses, how models are developed and validated, and how outputs are typically interpreted. The second part reviews recent modeling studies of the femur and proximal humerus, areas with particular relevance to fragility fractures. RECENT FINDINGS: There is some consensus in the literature around how certain modeling aspects are pragmatically formulated, including bone and implant geometries, meshing, material properties, interactions, and loads and boundary conditions. Studies most often focus on predicted implant stress, bone strain surrounding screws, or interfragmentary displacements. However, most models are not rigorously validated. With refined modeling methods, improved validation efforts, and large-scale systematic analyses, finite element analysis is poised to advance the understanding of fracture fixation failure, enable optimization of implant designs, and improve surgical guidance.

A quantitative evaluation of aerosol generation during tracheal intubation and extubation.

The potential aerosolised transmission of severe acute respiratory syndrome coronavirus-2 is of global concern. Airborne precaution personal protective equipment and preventative measures are universally mandated for medical procedures deemed to be aerosol generating. The implementation of these measures is having a huge impact on healthcare provision. There is currently a lack of quantitative evidence on the number and size of airborne particles produced during aerosol-generating procedures to inform risk assessments. To address this evidence gap, we conducted real-time, high-resolution environmental monitoring in ultraclean ventilation operating theatres during tracheal intubation and extubation sequences. Continuous sampling with an optical particle sizer allowed characterisation of aerosol generation within the zone between the patient and anaesthetist. Aerosol monitoring showed a very low background particle count (0.4 particles.l-1 ) allowing resolution of transient increases in airborne particles associated with airway management. As a positive reference control, we quantitated the aerosol produced in the same setting by a volitional cough (average concentration, 732 (418) particles.l-1 , n = 38). Tracheal intubation including facemask ventilation produced very low quantities of aerosolised particles (average concentration, 1.4 (1.4) particles.l-1 , n = 14, p < 0.0001 vs. cough). Tracheal extubation, particularly when the patient coughed, produced a detectable aerosol (21 (18) l-1 , n = 10) which was 15-fold greater than intubation (p = 0.0004) but 35-fold less than a volitional cough (p < 0.0001). The study does not support the designation of elective tracheal intubation as an aerosol-generating procedure. Extubation generates more detectable aerosol than intubation but falls below the current criterion for designation as a high-risk aerosol-generating procedure. These novel findings from real-time aerosol detection in a routine healthcare setting provide a quantitative methodology for risk assessment that can be extended to other airway management techniques and clinical settings. They also indicate the need for reappraisal of what constitutes an aerosol-generating procedure and the associated precautions for routine anaesthetic airway management.

A quantitative evaluation of aerosol generation during supraglottic airway insertion and removal.

Many guidelines consider supraglottic airway use to be an aerosol-generating procedure. This status requires increased levels of personal protective equipment, fallow time between cases and results in reduced operating theatre efficiency. Aerosol generation has never been quantitated during supraglottic airway use. To address this evidence gap, we conducted real-time aerosol monitoring (0.3-10-µm diameter) in ultraclean operating theatres during supraglottic airway insertion and removal. This showed very low background particle concentrations (median (IQR [range]) 1.6 (0-3.1 [0-4.0]) particles.l-1 ) against which the patient's tidal breathing produced a higher concentration of aerosol (4.0 (1.3-11.0 [0-44]) particles.l-1 , p = 0.048). The average aerosol concentration detected during supraglottic airway insertion (1.3 (1.0-4.2 [0-6.2]) particles.l-1 , n = 11), and removal (2.1 (0-17.5 [0-26.2]) particles.l-1 , n = 12) was no different to tidal breathing (p = 0.31 and p = 0.84, respectively). Comparison of supraglottic airway insertion and removal with a volitional cough (104 (66-169 [33-326]), n = 27), demonstrated that supraglottic airway insertion/removal sequences produced <4% of the aerosol compared with a single cough (p < 0.001). A transient aerosol increase was recorded during one complicated supraglottic airway insertion (which initially failed to provide a patent airway). Detailed analysis of this event showed an atypical particle size distribution and we subsequently identified multiple sources of non-respiratory aerosols that may be produced during airway management and can be considered as artefacts. These findings demonstrate supraglottic airway insertion/removal generates no more bio-aerosol than breathing and far less than a cough. This should inform the design of infection prevention strategies for anaesthetists and operating theatre staff caring for patients managed with supraglottic airways.