Using Simulations To Investigate Decision-making In Airline Operations

This paper examines a range of methods to collect data for the investigation of decision-making in airline Operations Control Centres (OCCs). A study was conducted of 52 controllers in five OCCs of both domestic and international airlines in the Asia-Pacific region. A range of methods was used including: surveys, interviews, observations, simulations, and think-aloud protocol. The paper compares and evaluates the suitability of these techniques for gathering data and provides recommendations on the application of simulations

Probing folded and unfolded states of outer membrane protein a with steady-state and time-resolved tryptophan fluorescence

Steady-state and time-resolved fluorescence measurements on each of five native tryptophan residues in full-length and truncated variants of E. coli outer-membrane protein A (OmpA) have been made in folded and denatured states. Tryptophan singlet excited-state lifetimes are multiexponential and vary among the residues. In addition, substantial increases in excited-state lifetimes accompany OmpA folding, with longer lifetimes in micelles than in phospholipid bilayers. This finding suggests that the Trp environments of OmpA folded in micelles and phospholipid bilayers are different. Measurements of Trp fluorescence decay kinetics with full-length OmpA folded in brominated lipid vesicles reveal that W102 is the most distant fluorophore from the hydrocarbon core, while W7 is the closest. Steady-state and time-resolved polarized fluorescence measurements indicate reduced Trp mobility when OmpA is folded in a micelle, and even lower mobility when the protein is folded in a bilayer. The fluorescence properties of truncated OmpA, in which the soluble periplasmic domain is removed, only modestly differ from those of the full-length form, suggesting similar folded structures for the two forms under these conditions

Mechanistic biomarkers provide early and sensitive detection of acetaminophen-induced acute liver injury at first presentation to hospital

Acetaminophen overdose is a common reason for hospital admission and the most frequent cause of hepatotoxicity in the Western world. Early identification would facilitate patient-individualized treatment strategies. We investigated the potential of a panel of novel biomarkers (with enhanced liver expression or linked to the mechanisms of toxicity) to identify patients with acetaminophen-induced acute liver injury (ALI) at first presentation to the hospital when currently used markers are within the normal range. In the first hospital presentation plasma sample from patients (n = 129), we measured microRNA-122 (miR-122; high liver specificity), high mobility group box-1 (HMGB1; marker of necrosis), full-length and caspase-cleaved keratin-18 (K18; markers of necrosis and apoptosis), and glutamate dehydrogenase (GLDH; marker of mitochondrial dysfunction). Receiver operator characteristic curve analysis and positive/negative predictive values were used to compare sensitivity to report liver injury versus alanine transaminase (ALT) and International Normalized Ratio (INR). In all patients, biomarkers at first presentation significantly correlated with peak ALT or INR. In patients presenting with normal ALT or INR, miR-122, HMGB1, and necrosis K18 identified the development of liver injury (n = 15) or not (n = 84) with a high degree of accuracy and significantly outperformed ALT, INR, and plasma acetaminophen concentration for the prediction of subsequent ALI (n = 11) compared with no ALI (n = 52) in patients presenting within 8 hours of overdose. Conclusion: Elevations in plasma miR-122, HMGB1, and necrosis K18 identified subsequent ALI development in patients on admission to the hospital, soon after acetaminophen overdose, and in patients with ALTs in the normal range. The application of such a biomarker panel could improve the speed of clinical decision-making, both in the treatment of ALI and the design/execution of patient-individualized treatment strategies

FORUM:Remote testing for psychological and physiological acoustics

Acoustics research involving human participants typically takes place in specialized laboratory settings. Listening studies, for example, may present controlled sounds using calibrated transducers in sound-attenuating or anechoic chambers. In contrast, remote testing takes place outside of the laboratory in everyday settings (e.g., participants' homes). Remote testing could provide greater access to participants, larger sample sizes, and opportunities to characterize performance in typical listening environments at the cost of reduced control of environmental conditions, less precise calibration, and inconsistency in attentional state and/or response behaviors from relatively smaller sample sizes and unintuitive experimental tasks. The Acoustical Society of America Technical Committee on Psychological and Physiological Acoustics launched the Task Force on Remote Testing (https://tcppasa.org/remotetesting/) in May 2020 with goals of surveying approaches and platforms available to support remote testing and identifying challenges and considerations for prospective investigators. The results of this task force survey were made available online in the form of a set of Wiki pages and summarized in this report. This report outlines the state-of-the-art of remote testing in auditory-related research as of August 2021, which is based on the Wiki and a literature search of papers published in this area since 2020, and provides three case studies to demonstrate feasibility during practice

AXR1-ECR1 and AXL1-ECR1 heterodimeric RUB-activating enzymes diverge in function in Arabidopsis thaliana

RELATED TO UBIQUITIN (RUB) modification of CULLIN (CUL) subunits of the CUL-RING ubiquitin E3 ligase (CRL) superfamily regulates CRL ubiquitylation activity. RUB modification requires E1 and E2 enzymes that are analogous to, but distinct from, those activities required for UBIQUITIN (UBQ) attachment. Gene duplications are widespread in angiosperms, and in line with this observation, components of the RUB conjugation pathway are found in multiples in Arabidopsis. To further examine the extent of redundancy within the RUB pathway, we undertook biochemical and genetic characterizations of one such duplication event- the duplication of the genes encoding a subunit of the RUB E1 into AUXIN RESISTANT1 (AXR1) and AXR1-LIKE1 (AXL1). In vitro, the two proteins have similar abilities to function with E1 C-TERMINAL-RELATED1 (ECR1) in catalyzing RUB1 activation and RUB1-ECR1 thioester formation. Using mass spectrometry, endogenous AXR1 and AXL1 proteins were found in complex with 3HA-RUB1, suggesting that AXR1 and AXL1 exist in parallel RUB E1 complexes in Arabidopsis. In contrast, AXR1 and AXL1 differ in ability to correct phenotypic defects in axr1-30, a severe loss-of-function AXR1 mutant, when the respective coding sequences are expressed from the same promoter, suggesting differential in vivo functions. These results suggest that while both proteins function in the RUB pathway and are biochemically similar in RUB-ECR1 thioester formation, they are not functionally equivalent

Effect of the UK's revised paracetamol poisoning management guidelines on admissions, adverse reactions and costs of treatment

AIMS: In September 2012 the UK’s Commission on Human Medicines (CHM) recommended changes in the management of paracetamol poisoning: use of a single ‘100 mg l(−1)’ nomogram treatment line, ceasing risk assessment, treating all staggered/uncertain ingestions and increasing the duration of the initial acetylcysteine (NAC) infusion from 15 to 60 min. We evaluated the effect of this on presentation, admission, treatment, adverse reactions and costs of paracetamol poisoning. METHODS: Data were prospectively collected from adult patients presenting to three large UK hospitals from 3 September 2011 to 3 September 2013 (year before and after change). Infusion duration effect on vomiting and anaphylactoid reactions was examined in one centre. A cost analysis from an NHS perspective was performed for 90 000 patients/annum with paracetamol overdose. RESULTS: There were increases in the numbers presenting to hospital (before 1703, after 1854; increase 8.9% [95% CI 1.9, 16.2], P = 0.011); admitted (1060/1703 [62.2%] vs. 1285/1854 [69.3%]; increase 7.1% [4.0, 10.2], P < 0.001) and proportion treated (626/1703 [36.8%] vs. 926/1854 [50.0%]; increase: 13.2% [95% CI 10.0, 16.4], P < 0.001). Increasing initial NAC infusion did not change the proportion of treated patients developing adverse reactions (15 min 87/323 [26.9%], 60 min 145/514 [28.2%]; increase: 1.3% [95% CI –4.9, 7.5], P = 0.682). Across the UK the estimated cost impact is £8.3 million (6.4 million–10.2 million) annually, with a cost-per-life saved of £17.4 million (13.4 million–21.5 million). CONCLUSIONS: The changes introduced by the CHM in September 2012 have increased the numbers of patients admitted to hospital and treated with acetylcysteine without reducing adverse reactions. A safety and cost-benefit review of the CHM guidance is warranted, including novel treatment protocols and biomarkers in the assessment of poisoning

Reduction of adverse effects from intravenous acetylcysteine treatment for paracetamol poisoning: a randomised controlled trial:a randomised controlled trial

Copyright © 2014 Bateman et al. Open Access article distributed under the terms of CC BY. Published by Elsevier Ltd. All rights reserved. The trial was funded by Chief Scientist Office, Scotland (award CZB/4/722).Peer reviewedPublisher PD

Understanding the Importance of Context:A Qualitative Study of a Location-Based Exergame to Enhance School Childrens Physical Activity

Many public health interventions are less effective than expected in 'real life settings', yet little work is undertaken to understand the reasons why. The effectiveness of complex public health interventions can often be traced back to a robust programme theory (how and why an intervention brings about a change in outcome(s)) and assumptions that are made about the context in which it is implemented. Understanding whether effectiveness (or lack thereof) is due to the intervention or the context is hugely helpful in decisions about whether to a) modify the intervention; b) modify the context; c) stop providing the intervention. Exergames-also known as Active Video Games or AVGS-are video games which use the player's bodily movements as input and have potential to increase physical activity in children. However, the results of a recent pilot randomised controlled trial (RCT) of a location-based exergame (FitQuest) in a school setting were inconclusive; no significant effect was detected for any of the outcome measures. The aim of this study was to explore whether the programme theory for FitQuest was correct with respect to how and why it would change children's perceptions of physical activity (PA) and exercise self-efficacy in the school setting. A further aim was to investigate the features of the school setting (context) that may impact on FitQuest's implementation and effectiveness. Qualitative data (gathered during the RCT) were gathered from interviews with teachers and children, and observation of sessions using FitQuest. Thematic analysis indicated that whilst children enjoyed playing the game, engaged with goal setting within the game context and undertook low to vigorous physical activity, there were significant contextual factors that prevented it from being played as often as intended. These included environmental factors (e.g. size of the playground), school factors (cancellations due to other activities), school technology policy (rules relating to mobile phone usage) and teacher factors (engagement with the intervention). A revised logic model for the FitQuest intervention indicates how both the design of exergame technology (intervention) and features of the school environment (context) could be improved to increase chances of effectiveness in the future

Common Genetic Polymorphisms Influence Blood Biomarker Measurements in COPD

Implementing precision medicine for complex diseases such as chronic obstructive lung disease (COPD) will require extensive use of biomarkers and an in-depth understanding of how genetic, epigenetic, and environmental variations contribute to phenotypic diversity and disease progression. A meta-analysis from two large cohorts of current and former smokers with and without COPD [SPIROMICS (N = 750); COPDGene (N = 590)] was used to identify single nucleotide polymorphisms (SNPs) associated with measurement of 88 blood proteins (protein quantitative trait loci; pQTLs). PQTLs consistently replicated between the two cohorts. Features of pQTLs were compared to previously reported expression QTLs (eQTLs). Inference of causal relations of pQTL genotypes, biomarker measurements, and four clinical COPD phenotypes (airflow obstruction, emphysema, exacerbation history, and chronic bronchitis) were explored using conditional independence tests. We identified 527 highly significant (p 10% of measured variation in 13 protein biomarkers, with a single SNP (rs7041; p = 10−392) explaining 71%-75% of the measured variation in vitamin D binding protein (gene = GC). Some of these pQTLs [e.g., pQTLs for VDBP, sRAGE (gene = AGER), surfactant protein D (gene = SFTPD), and TNFRSF10C] have been previously associated with COPD phenotypes. Most pQTLs were local (cis), but distant (trans) pQTL SNPs in the ABO blood group locus were the top pQTL SNPs for five proteins. The inclusion of pQTL SNPs improved the clinical predictive value for the established association of sRAGE and emphysema, and the explanation of variance (R2) for emphysema improved from 0.3 to 0.4 when the pQTL SNP was included in the model along with clinical covariates. Causal modeling provided insight into specific pQTL-disease relationships for airflow obstruction and emphysema. In conclusion, given the frequency of highly significant local pQTLs, the large amount of variance potentially explained by pQTL, and the differences observed between pQTLs and eQTLs SNPs, we recommend that protein biomarker-disease association studies take into account the potential effect of common local SNPs and that pQTLs be integrated along with eQTLs to uncover disease mechanisms. Large-scale blood biomarker studies would also benefit from close attention to the ABO blood group

Evaluation of lung MDCT nodule annotation across radiologists and methods

RATIONALE AND OBJECTIVES: Integral to the mission of the National Institutes of Health–sponsored Lung Imaging Database Consortium is the accurate definition of the spatial location of pulmonary nodules. Because the majority of small lung nodules are not resected, a reference standard from histopathology is generally unavailable. Thus assessing the source of variability in defining the spatial location of lung nodules by expert radiologists using different software tools as an alternative form of truth is necessary. MATERIALS AND METHODS: The relative differences in performance of six radiologists each applying three annotation methods to the task of defining the spatial extent of 23 different lung nodules were evaluated. The variability of radiologists’ spatial definitions for a nodule was measured using both volumes and probability maps (p-map). Results were analyzed using a linear mixed-effects model that included nested random effects. RESULTS: Across the combination of all nodules, volume and p-map model parameters were found to be significant at P < .05 for all methods, all radiologists, and all second-order interactions except one. The radiologist and methods variables accounted for 15% and 3.5% of the total p-map variance, respectively, and 40.4% and 31.1% of the total volume variance, respectively. CONCLUSION: Radiologists represent the major source of variance as compared with drawing tools independent of drawing metric used. Although the random noise component is larger for the p-map analysis than for volume estimation, the p-map analysis appears to have more power to detect differences in radiologist-method combinations. The standard deviation of the volume measurement task appears to be proportional to nodule volume