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Background: The COVID-19 pandemic has revealed the fragility of the global food system, sending shockwaves across countries' societies and economy. This has presented formidable challenges to sustaining a healthy and resilient lifestyle. The objective of this study is to examine the food consumption patterns and assess diet diversity indicators, primarily focusing on the food consumption score (FCS), among households in 38 countries both before and during the first wave of the COVID-19 pandemic. Methods: A cross-sectional study with 37 207 participants (mean age: 36.70 ± 14.79, with 77 % women) was conducted in 38 countries through an online survey administered between April and June 2020. The study utilized a pre-tested food frequency questionnaire to explore food consumption patterns both before and during the COVID-19 periods. Additionally, the study computed Food Consumption Score (FCS) as a proxy indicator for assessing the dietary diversity of households. Findings: This quantification of global, regional and national dietary diversity across 38 countries showed an increment in the consumption of all food groups but a drop in the intake of vegetables and in the dietary diversity. The household's food consumption scores indicating dietary diversity varied across regions. It decreased in the Middle East and North Africa (MENA) countries, including Lebanon (p

The application of augmented reality (AR) is receiving great interest in e-commerce, m-commerce, and brick-and-mortar-retailing. A growing body of literature has explored several different facets of how consumers react to the upcoming augmented shopping reality. This systematic literature review summarizes the findings of 56 empirical papers that analyzed consumers’ experience with AR, acceptance of AR, and behavioral reactions to AR in various online and offline environments. The review synthesizes current knowledge and critically discusses the empirical studies conceptually and methodologically. Finally, the review outlines the theoretical basis as well as the independent, mediating, moderating, and dependent variables analyzed in previous AR research. Based on this synthesis, the paper develops an integrative framework model, which helps derive directives for future research on augmented shopping reality.

Tar in the product gas of biomass gasifiers reduces the efficiency of gasification processes and causes fouling of system components and pipework. Therefore, an efficient tar conversion in the product gas is a key step of effective and reliable syngas production. One of the most promising approaches is the catalytic decomposition of the tar species combined with hot syngas cleaning. The catalyst must be able to convert tar components in the synthesis gas at temperatures of around 700 °C downstream of the gasifier without preheating. A Ni-based doped catalyst with high activity in tar conversion was developed and characterized in detail. An appropriate composition of transition metals was applied to minimize catalyst coking. Precious metals (Pt, Pd, Rh, or a combination of two of them) were added to the catalyst in small quantities. Depending on the hot gas cleaning system used, both transition metals and precious metals were co-impregnated on pellets or on a ceramic filter material. In the case of a pelletized-type catalyst, the hot gas cleaning system revealed a conversion above 80% for 70 and 110 h. The catalyst composed of Ni, Fe, and Cr oxides, promoted with Pt and impregnated on a ceramic fiber filter composed of Al2O3(44%)/SiO2(56%), was the most active catalyst for a compact cleaning system. This catalyst was catalytically active with a naphthalene conversion of around 93% over 95 h without catalyst deactivation.

Abstract Bioadhesive materials and patches are promising alternatives to surgical sutures and staples. However, many existing bioadhesives do not meet the functional requirements of current surgical procedures and interventions. Here, we present a translational patch material that exhibits instant adhesion to tissues (2.5-fold stronger than Tisseel, an FDA-approved fibrin glue), ultra-stretchability (stretching to >300% its original length without losing elasticity), compatibility with rapid photo-projection (

Abstract It is increasingly important to monitor sliding interfaces within machines, since this is where both energy is lost, and failures occur. Acoustic emission (AE) techniques offer a way to monitor contacts remotely without requiring transparent or electrically conductive materials. However, acoustic data from sliding contacts is notoriously complex and difficult to interpret. Herein, we simultaneously measure coefficient of friction (with a conventional force transducer) and acoustic emission (with a piezoelectric sensor and high acquisition rate digitizer) produced by a steel–steel rubbing contact. Acquired data is then used to train machine learning (ML) algorithms (e.g., Gaussian process regression (GPR) and support vector machine (SVM)) to correlated acoustic emission with friction. ML training requires the dense AE data to first be reduced in size and a range of processing techniques are assessed for this (e.g., down-sampling, averaging, fast Fourier transforms (FFTs), histograms). Next, fresh, unseen AE data is given to the trained model and the resulting friction predictions are compared with the directly measured friction. There is excellent agreement between the measured and predicted friction when the GPR model is used on AE histogram data, with root mean square (RMS) errors as low as 0.03 and Pearson correlation coefficients reaching 0.8. Moreover, predictions remain accurate despite changes in test conditions such as normal load, reciprocating frequency, and stroke length. This paves the way for remote, acoustic measurements of friction in inaccessible locations within machinery to increase mechanical efficiency and avoid costly failure/needless maintenance.

Abstract Background Allergic diseases impose a significant global disease burden, however, the influence of light at night exposure on these diseases in humans has not been comprehensively assessed. We aimed to summarize available evidence considering the association between light at night exposure and major allergic diseases through a systematic review and meta-analysis. Methods We completed a search of six databases, two registries, and Google Scholar from inception until December 15, 2023, and included studies that investigated the influence of artificial light at night (ALAN, high vs. low exposure), chronotype (evening vs. morning chronotype), or shift work (night vs. day shift work) on allergic disease outcomes (asthma, allergic rhinitis, and skin allergies). We performed inverse-variance random-effects meta-analyses to examine the association between the exposures (ALAN exposure, chronotype, or shiftwork) and these allergic outcomes. Stratification analyses were conducted by exposure type, disease type, participant age, and geographical location along with sensitivity analyses to assess publication bias. Results We included 12 publications in our review. We found that exposure to light at night was associated with higher odds of allergic diseases, with the strongest association observed for ALAN exposure (OR: 1.88; 95% CI: 1.04 to 3.39), followed by evening chronotype (OR: 1.35; 95% CI: 0.98 to 1.87) and exposure to night shift work (OR: 1.33; 95% CI: 1.06 to 1.67). When analyses were stratified by disease types, light at night exposure was significantly associated with asthma (OR: 1.62; 95% CI: 1.19 to 2.20), allergic rhinitis (OR: 1.89; 95% CI: 1.60 to 2.24), and skin allergies (OR: 1.11; 95% CI: 1.09 to 1.91). We also found that the association between light at night exposure and allergic diseases was more profound in youth (OR: 1.63; 95% CI: 1.07 to 2.48) than adults (OR: 1.30; 95% CI: 1.03 to 1.63). Additionally, we observed significant geographical variations in the association between light at night exposure and allergic diseases. Conclusions Light at night exposure was associated with a higher prevalence of allergic diseases, both in youth and adults. More long-term epidemiological and mechanistic research is required to understand the possible interactions between light at night and allergic diseases.

Background and aims: Non-alcoholic fatty liver disease (NAFLD) has rapidly become the most common liver disease worldwide. Modern lifestyles have been linked to this rise in prevalence with changes in rhythmic human behaviour emerging as a possible mechanism. We investigated how shift working patterns and chronotype were associated with hepatic fat fraction and NAFLD in 282,303 UK Biobank participants. Methods: We stratified participants into day, irregular-shift, and permanent night-shift workers. We then utilised multiple methods of disease identification including (i) Dallas steatosis index (DSI), (ii) ICD10 codes, and (iii) hepatic proton density fat fraction (PDFF) and examined how shift work exposure impacted these variables. We further assessed the relationship of baseline chronotype with liver phenotypes using these same outcome measures. Results: Compared to day workers, irregular-shift workers were more likely to have a high DSI (OR 1.29 (1.2–1.4)) after adjusting for major covariates with some attenuation after additional adjustment for BMI (OR 1.12 (1.03–1.22)). Likelihood of high DSI was also increased in permanent night-shift workers (OR 1.08 (0.9–1.29)) in the fully adjusted model. Mediator analysis revealed that BMI was a significant mediator of the shift work effect. Compared to participants with intermediate chronotype, those with extreme late chronotype had a higher likelihood of high DSI defined NAFLD (OR 1.45 (1.34–1.56)) and a higher likelihood of NAFLD/NASH by ICD10 code (OR 1.23 (1.09–1.39)). Hepatic PDFF was elevated in irregular shift workers, but not permanent night-shift workers. Conclusions: Irregular-shift work and extreme late chronotype are associated with pathological liver fat accumulation, suggesting circadian misalignment may have an underlying pathogenic role. These findings have implications for health interventions to mitigate the detrimental effect of shift work.

IntroductionSepsis engenders distinct host immunologic changes that include the expansion of myeloid-derived suppressor cells (MDSCs). These cells play a physiologic role in tempering acute inflammatory responses but can persist in patients who develop chronic critical illness.MethodsCellular Indexing of Transcriptomes and Epitopes by Sequencing and transcriptomic analysis are used to describe MDSC subpopulations based on differential gene expression, RNA velocities, and biologic process clustering.ResultsWe identify a unique lineage and differentiation pathway for MDSCs after sepsis and describe a novel MDSC subpopulation. Additionally, we report that the heterogeneous response of the myeloid compartment of blood to sepsis is dependent on clinical outcome.DiscussionThe origins and lineage of these MDSC subpopulations were previously assumed to be discrete and unidirectional; however, these cells exhibit a dynamic phenotype with considerable plasticity.

This study explores the correlation between social categories and linguistic variables, focusing on the perception of the discourse marker yeah-no in Australian English. Research suggests that these correlations reflect individuals’ recruitment of variables for the purpose of communicating social meaning. However, not all social categories which correlate with a variable in production are recognizable as social meaning. This study investigated how individuals’ positioning to a variable mediates their awareness to its social meaning by examining perceptions of gender and life-stage in yeah-no users and non-users. We found that individuals judged sentences including yeah-no as more likely to be said by a student, and this effect was stronger for individuals who did not self-report as yeah-no users. Furthermore, while there was no significant effect of gender, participants who did not self-report as yeah-no users were more likely to judge yeah-no sentences as said by a male speaker rather than a female speaker. The findings imply that the perception of social meaning is influenced by an individual’s positioning towards a variable. More broadly, the results provide support for using self-report techniques in the investigation of social meaning.

Introduction: The skin is the largest organ of the human body and fulfills protective, immune, and metabolic functions. Skin function and barrier integrity are actively regulated through circadian rhythm–associated genes and epigenetic mechanisms including DNA methylation/demethylation, histone acetylation/deacetylation, and microRNAs. MicroRNA-146a-5p (miR-146a) has been associated with immune activation and skin inflammation; however, the role of miR-146a in regulating skin aging is an open question. This study investigated the role of miR-146a in fibroblasts obtained from different donors in the context of aging, and a potential association of this miRNA with circadian rhythm.Methods: Normal human dermal fibroblasts (NHDFs) from 19y, 27y, 40y, and 62y old donors were used to analyze for miR-146a expression. Expression of miR-146a was downregulated with the hsa-mirVana miR-146a inhibitor, and upregulated with an extract from Adansonia digitata. Effects on markers of skin aging, including cell proliferation, production of Collagen-1 and inflammatory cytokines were assessed.Results: We show that the expression of miR-146a decreases with age in dermal fibroblasts and inhibition of miR-146a in 19y and 62y old NHDFs induced significant changes in essential clock genes indicating an association with circadian rhythm control. Furthermore, downregulation of miR-146a results in a reduction of cellular proliferation, Collagen-1 production, as well as an increase in DNA damage and pro-inflammatory markers. Activation of miR-146a with the Adansonia digitata extract reduced the deleterious effects seen during miR-146a inhibition and increased miR-146a transport through exosome transfer.Conclusion: miR-146a interacts with multiple biological pathways related to skin aging, including circadian rhythm machinery, cell-to-cell communication, cell damage repair, cell proliferation, and collagen production and represents a promising target to fight skin aging. Adansonia digitata extract can promote miR-146a expression and therefore support skin cells’ health.

f-statistics have emerged as a first line of analysis for making inferences about demographic history from genome-wide data. Not only are they guaranteed to allow robust tests of the fits of proposed models of population history to data when analyzing full genome sequencing data-that is, all single nucleotide polymorphisms (SNPs) in the individuals being analyzed-but they are also guaranteed to allow robust tests of models for SNPs ascertained as polymorphic in a population that is an outgroup in a phylogenetic sense to all groups being analyzed. True "outgroup ascertainment" is in practice impossible in humans because our species has arisen from a substructured ancestral population that does not descend from a homogeneous ancestral population going back many hundreds of thousands of years into the past. However, initial studies suggested that non-outgroup-ascertainment schemes might produce robust enough results using f-statistics, and that motivated widespread fitting of models to data using non-outgroup-ascertained SNP panels such as the "Affymetrix Human Origins array" which has been genotyped on thousands of modern individuals from hundreds of populations, or the "1240k" in-solution enrichment reagent which has been the source of about 70% of published genome-wide data for ancient humans. In this study, we show that while analyses of population history using such panels work well for studies of relationships among non-African populations and one African outgroup, when co-modeling more than one sub-Saharan African and/or archaic human groups (Neanderthals and Denisovans), fitting of f-statistics to such SNP sets is expected to frequently lead to false rejection of true demographic histories, and failure to reject incorrect models. Analyzing panels of SNPs polymorphic in archaic humans, which has been suggested as a solution for the ascertainment problem, has limited statistical power and retains important biases. However, by carrying out simulations of diverse demographic histories, we show that bias in inferences based on f-statistics can be minimized by ascertaining on variants common in a union of diverse African groups; such ascertainment retains high statistical power while allowing co-analysis of archaic and modern groups.

Acute radiation syndrome (ARS) develops after exposure to high doses of ionizing radiation and features immune suppression and organ failure. Currently, there are no diagnostics to identify the occurrence or severity of exposure and there are limited treatments and preventative strategies to mitigate ARS. Extracellular vesicles (EVs) are mediators of intercellular communication that contribute to immune dysfunction across many diseases. We investigated if EV cargo can identify whole body irradiation (WBIR) exposure and if EVs promote ARS immune dysfunction. We hypothesized that beneficial EVs derived from mesenchymal stem cells (MSC-EVs) would blunt ARS immune dysfunction and might serve as prophylactic radioprotectants. Mice received WBIR (2 or 9 Gy) with assessment of EVs at 3 and 7 days after exposure. LC-MS/MS proteomic analysis of WBIR-EVs found dose-related changes as well as candidate proteins that were increased with both doses and timepoints (34 total) such as Thromboxane-A Synthase and lymphocyte cytosolic protein 2. Suprabasin and Sarcalumenin were increased only after 9 Gy suggesting these proteins may indicate high dose/lethal exposure. Analysis of EV miRNAs identified miR-376 and miR-136, which were increased up to 200- and 60-fold respectively by both doses of WBIR and select miRNAs such as miR-1839 and miR-664 were increased only with 9 Gy. WBIR-EVs (9 Gy) were biologically active and blunted immune responses to LPS in RAW264.7 macrophages, inhibiting canonical signaling pathways associated with wound healing and phagosome formation. When given 3 days after exposure, MSC-EVs slightly modified immune gene expression changes in the spleens of mice in response to WBIR and in a combined radiation plus burn injury exposure (RCI). MSC-EVs normalized the expression of certain key immune genes such as NFκBia and Cxcr4 (WBIR), Map4k1, Ccr9 and Cxcl12 (RCI) and lowered plasma TNFα cytokine levels after RCI. When given prophylactically (24 and 3 hours before exposure), MSC-EVs prolonged survival to the 9 Gy lethal exposure. Thus, EVs are important participants in ARS. EV cargo might be used to diagnose WBIR exposure, and MSC-EVs might serve as radioprotectants to blunt the impact of toxic radiation exposure.

The reason for the failure of electric vehicle drives is increasingly current-induced damage to rolling bearings. Studies show that rolling bearings are more susceptible to current pass-through after the first occurrence of unwanted bearing currents. To investigate this effect, a test plan is introduced with variations in axial and radial loads, as well as rotational speeds. A new bearing is mechanically run-in for each test point and then subjected to a realistic voltage signal of gradually increasing amplitude. After the initial breakdown, the different voltage amplitudes are applied again to investigate the behavior after the initial breakdown. During the whole test, the maximum current, the duration and the dissipated energy of each breakdown are measured. The results provide insights into the processes after the initial breakdown and the stochastic nature of the breakdown behavior.

Abstract Background The use of formal coercion such as seclusion, mechanical restraint, and forced medication is one of the most challenging and complex issues in mental health care, on the clinical, the legal, and the ethical level. Clinical ethics support aims at assisting healthcare practitioners in determining the morally most justifiable course of action in these situations. However, the effectiveness of clinical ethics support has hardly been studied so far. Methods Monthly moral case deliberation (MCD) was implemented in two acute wards of two different psychiatric hospitals in Switzerland. Frequency and intensity of coercion was measured on ward level (n patients = 405), and the Moral Attentiveness Scale, Knowledge on Coercion Scale, and Staff Attitudes towards Coercion Scale were applied on healthcare practitioner level (n HP = 46). Pre-post-comparisons were conducted using multi-level modeling where appropriate. Results After implementation of MCD, formal coercion was less frequent (particularly seclusion, small effect size; 9.6 vs. 16.7%, p = .034, Cramér’s V = .105) and less intense (particularly mechanical restraint, large effect size; 86.8 ± 45.3 vs. 14.5 ± 12.1 h, exact p = .019, r = -.74), and approval for coercive measures among healthcare practitioners was lower when controlling for the number of MCD sessions attended. Conclusions Clinical ethics support such as MCD may be a hitherto underutilized service for the reduction of coercion, complementing existing strategies and programs. Implementing clinical ethics support may help improve quality of care for persons suffering from severe mental illness.

Our understanding of population history in deep time has been assisted by fitting admixture graphs (AGs) to data: models that specify the ordering of population splits and mixtures, which along with the amount of genetic drift and the proportions of mixture, is the only information needed to predict the patterns of allele frequency correlation among populations. The space of possible AGs relating populations is vast, and thus most published studies have identified fitting AGs through a manual process driven by prior hypotheses, leaving the majority of alternative models unexplored. Here, we develop a method for systematically searching the space of all AGs that can incorporate non-genetic information in the form of topology constraints. We implement this findGraphs tool within a software package, ADMIXTOOLS 2, which is a reimplementation of the ADMIXTOOLS software with new features and large performance gains. We apply this methodology to identify alternative models to AGs that played key roles in eight publications and find that in nearly all cases many alternative models fit nominally or significantly better than the published one. Our results suggest that strong claims about population history from AGs should only be made when all well-fitting and temporally plausible models share common topological features. Our re-evaluation of published data also provides insight into the population histories of humans, dogs, and horses, identifying features that are stable across the models we explored, as well as scenarios of populations relationships that differ in important ways from models that have been highlighted in the literature.

Abstract Covalent functionalisation can be a powerful lever to tune the properties and processability of graphene. After overcoming the low chemical reactivity of graphene, covalent functionalisation led to the generation of new hybrid materials, applicable in a broad variation of fields. Although the process of functionalising graphene is nowadays firmly established, fundamental aspects of the produced hybrid materials remain to be clarified. Especially the atomically resolved imaging is only scarcely explored. Here we show aberration corrected in situ high resolution TEM imaging of dodecyl functionalised monolayer graphene at atomic resolution after an effective mechanical filtering approach. The mechanical filtering allows to separate adsorbed contamination from the covalently bound functional molecules and thus opens the possibility for the observation of this hybrid material. The obtained data is validated by DFT calculations and by a novel image simulation approach based on molecular dynamics (MD) simulations at room temperature.

Background Early in the pandemic, transmission risk from asymptomatic infection was unclear, making it imperative to monitor infection in workplace settings. Further, data on SARS-CoV-2 seroprevalence within university populations has been limited. Methods We performed a longitudinal study of University research employees on campus July-December 2020. We conducted questionnaires on COVID-19 risk factors, RT-PCR testing, and SARS-CoV-2 serology using an in-house spike RBD assay, laboratory-based Spike NTD assay, and standard nucleocapsid platform assay. We estimated prevalence and cumulative incidence of seroconversion with 95% confidence intervals using the inverse of the Kaplan-Meier estimator. Results 910 individuals were included in this analysis. At baseline, 6.2% (95% CI 4.29–8.19) were seropositive using the spike RBD assay; four (0.4%) were seropositive using the nucleocapsid assay, and 44 (4.8%) using the Spike NTD assay. Cumulative incidence was 3.61% (95% CI: 2.04–5.16). Six asymptomatic individuals had positive RT-PCR results. Conclusions Prevalence and incidence of SARS-CoV-2 infections were low; however, differences in target antigens of serological tests provided different estimates. Future research on appropriate methods of serological testing in unvaccinated and vaccinated populations is needed. Frequent RT-PCR testing of asymptomatic individuals is required to detect acute infections, and repeated serosurveys are beneficial for monitoring subclinical infection.

The Crab Pulsar is the prime example of an emitter of giant pulses. These short, very bright pulses are thought to originate near the light cylinder, at ∼1600 km from the pulsar. The pulsar’s location inside the Crab Nebula offers an unusual opportunity to resolve the emission regions, using the nebula, which scatters radio waves, as a lens. We attempt to do this using a sample of 61,998 giant pulses found in coherently combined European VLBI network observations at 18 cm. These were taken at times of relatively strong scattering and hence good effective resolution. From correlations between pulse spectra, we show that the giant pulse emission regions are indeed resolved. We infer apparent diameters of ∼2000 and ∼2400 km for the main and interpulse components, respectively, and show that with these sizes the correlation amplitudes and decorrelation timescales and bandwidths can be understood quantitatively, both in our observations and in previous ones. Using pulse-spectra statistics and correlations between polarizations, we also show that the nebula resolves the nanoshots that comprise individual giant pulses. The implied diameters of ∼1100 km far exceed light-travel-time estimates, suggesting the emitting plasma is moving relativistically, with γ ≃ 10 ^4 , as inferred previously from drifting bands during the scattering tail of a giant pulse. If so, the emission happens over a region extended along the line of sight by ∼10 ^7 km. We conclude that relativistic motion likely is important for producing giant pulses, and may be similarly for other sources of short, bright radio emission, such as fast radio bursts.

According to the European Commission, Austria is obliged to reduce ammonia emissions by 12% between 2005 and 2030. Agriculture, in particular livestock buildings and the spreading of manure, is the predominant source of ammonia in most countries, calling for stringent mitigation measures in this area. This study investigated a combination of measures implemented in a newly constructed fattening piggery in Styria (Austria) for reducing ammonia, particulate matter (not subject of this publication), and odour emissions. Additionally, the livestock building should meet standards to enhance animal welfare as well. Based on observed ammonia concentrations at several locations in the vicinity of the farm as well as field inspections for odour according to EN 16841-1, corresponding emission factors were derived using the Lagrangian particle model GRAL and in situ measurements of meteorology. The resulting emission factor for ammonia was found to be 80% lower compared to the standard emission factor of 3.64 kg a−1 for fattening piggeries according to the German guideline VDI 3894-1. Moreover, the emission factor for odour was 95% lower than the standard factor of 0.180 ouE kg−1 s−1 used in Styria for conventional fattening piggeries without any reduction techniques.

Summary: MicroRNAs (miRNAs) are small non-coding RNAs involved in post-transcriptional gene regulation that have a major impact on many diseases and provide an exciting avenue toward antiviral therapeutics. From patient transcriptomic data, we determined that a circulating miRNA, miR-2392, is directly involved with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) machinery during host infection. Specifically, we show that miR-2392 is key in driving downstream suppression of mitochondrial gene expression, increasing inflammation, glycolysis, and hypoxia, as well as promoting many symptoms associated with coronavirus disease 2019 (COVID-19) infection. We demonstrate that miR-2392 is present in the blood and urine of patients positive for COVID-19 but is not present in patients negative for COVID-19. These findings indicate the potential for developing a minimally invasive COVID-19 detection method. Lastly, using in vitro human and in vivo hamster models, we design a miRNA-based antiviral therapeutic that targets miR-2392, significantly reduces SARS-CoV-2 viability in hamsters, and may potentially inhibit a COVID-19 disease state in humans.

An extreme sub-daily precipitation event produced about 300 mm of rainfall in less than 4 h overnight from 13–14 February 2019 resulting in high floods in Thohoyandou, a small town northeast of South Africa. We employed station, radar, satellite and reanalysis datasets to investigate the rainfall, circulation and thermodynamic fields and understand the meteorological structure of the extreme event via a multiscale analysis. The large-scale synoptic environment was characterized by a mid-tropospheric tropical-temperate trough and attendant cloud band coupled to a surface high ridging over the southeast coast of the country. We found that whilst heavy rainfall (>50 mm/24 h) was widespread ahead of the upper trough, extreme amounts (∼100 mm/h) were localized due to a cloudburst. A small perturbation to the favorable large scale mid-tropospheric environment also contributed to localized heavy rainfall. The south-north pressure gradient was steepened by a surface low over southern Mozambique resulting in enhanced moisture fluxes deriving from the southwest Indian Ocean. The interaction of prevailing surface winds and a low-level jet with the steep topography of the adjacent Soutpansberg Mountain Range enhanced low-level convergence and lifting in the area. We also show that the highest rainfalls were uphill of the location of flooding which was contained in a poorly drained valley. Whereas the Unified Model forecasts appeared accurate for the large-scale pattern of heavy rainfall in the area, the rainfall peak was generally underestimated, whilst the timing of extreme rainfall was delayed in the 18Z simulation, which is used by forecasters operationally. Our findings contribute to understanding the occurrence of extreme weather events over northeastern South Africa and also how models treat them, towards natural disaster risk reduction.

Numerical weather prediction (NWP) models have been increasing in skill and their capability to simulate weather systems and provide valuable information at convective scales has improved in recent years. Much effort has been put into developing NWP models across the globe. Representation of physical processes is one of the critical issues in NWP, and it differs from one model to another. We investigated the performance of three regional NWP models used by the South African Weather Service over southern Africa, to identify the model that produces the best deterministic forecasts for the study domain. The three models – Unified Model (UM), Consortium for Small-scale Modelling (COSMO) and Weather Research and Forecasting (WRF) – were run at a horizontal grid spacing of about 4.4 km. Model forecasts for precipitation, 2-m temperature, and wind speed were verified against different observations. Snow was evaluated against reported snow records. Both the temporal and spatial verification of the model forecasts showed that the three models are comparable, with slight variations. Temperature and wind speed forecasts were similar for the three different models. Accumulated precipitation was mostly similar, except where WRF captured small rainfall amounts from a coastal low, while it over-estimated rainfall over the ocean. The UM showed a bubble-like shape towards the tropics, while COSMO cut-off part of the rainfall band that extended from the tropics to the sub-tropics. The COSMO and WRF models simulated a larger spatial coverage of precipitation than UM and snow-report records. Significance: • Extreme weather events, such as tornadoes, floods, strong winds and heat waves, have significant impacts on society, the economy, infrastructure, agriculture and many other sectors. These impacts may be mitigated or even prevented through early warning systems which depend on the use of weather forecasts and information from NWP models. As South Africa depends on models from developed countries, these models may have shortcomings in capturing extreme weather events over the southern African region.

Warnings of severe weather with a lead time longer that two hours require the use of skillful numerical weather prediction (NWP) models. In this study, we test the performance of the Commonwealth Scientific and Industrial Research Organisation (CSIRO) Conformal Cubic Atmospheric Model (CCAM) in simulating six high-impact weather events, with a focus on rainfall predictions in South Africa. The selected events are tropical cyclone Dineo (16 February 2017), the Cape storm (7 June 2017), the 2017 Kwa-Zulu Natal (KZN) floods (10 October 2017), the 2019 KZN floods (22 April 2019), the 2019 KZN tornadoes (12 November 2019) and the 2020 Johannesburg floods (5 October 2020). Three configurations of CCAM were compared: a 9 km grid length (MN9km) over southern Africa nudged within the Global Forecast System (GFS) simulations, and a 3 km grid length over South Africa (MN3km) nudged within the 9 km CCAM simulations. The last configuration is CCAM running with a grid length of 3 km over South Africa, which is nudged within the GFS (SN3km). The GFS is available with a grid length of 0.25°, and therefore, the configurations allow us to test if there is benefit in the intermediate nudging at 9 km as well as the effects of resolution on rainfall simulations. The South African Weather Service (SAWS) station rainfall dataset is used for verification purposes. All three configurations of CCAM are generally able to capture the spatial pattern of rainfall associated with each of the events. However, the maximum rainfall associated with two of the heaviest rainfall events is underestimated by CCAM with more than 100 mm. CCAM simulations also have some shortcomings with capturing the location of heavy rainfall inland and along the northeast coast of the country. Similar shortcomings were found with other NWP models used in southern Africa for operational forecasting purposes by previous studies. CCAM generally simulates a larger rainfall area than observed, resulting in more stations reporting rainfall. Regarding the different configurations, they are more similar to one another than observations, however, with some suggestion that MN3km outperforms other configurations, in particular with capturing the most extreme events. The performance of CCAM in the convective scales is encouraging, and further studies will be conducted to identify areas of possible improvement.

Implantable glucose biosensors provide real-time information about blood glucose fluctuations, but their utility and accuracy are time-limited due to the foreign body response (FBR) following their insertion beneath the skin. The slow release of nitric oxide (NO), a gasotransmitter with inflammation regulatory properties, from a sensor surface has been shown to dramatically improve sensors’ analytical biocompatibility by reducing the overall FBR response. Indeed, work in a porcine model suggests that as long as the implants (sensors) continue to release NO, even at low levels, the inflammatory cell infiltration and resulting collagen density are lessened. While these studies strongly support the benefits of NO release in mitigating the FBR, the mechanisms through which exogenous NO acts on the surrounding tissue, especially under the condition of hyperglycemia, remain vague. Such knowledge would inform strategies to refine appropriate NO dosage and release kinetics for optimal therapeutic activity. In this study, we evaluated mediator, immune cell, and mRNA expression profiles in the local tissue microenvironment surrounding implanted sensors as a function of NO release, diabetes, and implantation duration. A custom porcine wound healing-centric multiplex gene array was developed for nanoString barcoding analysis. Tissues adjacent to sensors with sustained NO release abrogated the implant-induced acute and chronic FBR through modulation of the tissue-specific immune chemokine and cytokine microenvironment, resulting in decreased cellular recruitment, proliferation, and activation at both the acute (7-d) and chronic (14-d) phases of the FBR. Further, we found that sustained NO release abrogated the implant-induced acute and chronic foreign body response through modulation of mRNA encoding for key immunological signaling molecules and pathways, including STAT1 and multiple STAT1 targets including MAPK14, IRAK4, MMP2, and CXCL10. The condition of diabetes promoted a more robust FBR to the implants, which was also controlled by sustained NO release.

Abstract Objective We applied systems biology approaches to investigate circadian rhythmicity in rheumatoid arthritis (RA). Methods We recruited adults (age 16–80 years old) with a clinical diagnosis of RA (active disease [DAS28 > 3.2]). Sleep profiles were determined before inpatient measurements of saliva, serum, and peripheral blood mononuclear leukocytes (PBML). Transcriptome and proteome analyses were carried out by RNA-SEQ and LC-MS/MS. Serum samples were analysed by targeted lipidomics, along with serum from mouse collagen induced-arthritis (CIA). Bioinformatic analysis identified RA-specific gene networks and rhythmic processes differing between healthy and RA. Results RA caused greater time-of-day variation in PBML gene expression, and ex vivo stimulation identified a time-of-day-specific RA transcriptome. We found increased phospho-STAT3 in RA patients, and some targets, including phospho-ATF2, acquired time-of-day variation in RA. Serum ceramides also gained circadian rhythmicity in RA, which was also seen in mouse experimental arthritis, resulting from gain in circadian rhythmicity of hepatic ceramide synthases. Conclusion RA drives a gain in circadian rhythmicity, both in immune cells, and systemically. The coupling of distant timing information to ceramide synthesis and joint inflammation points to a systemic re-wiring of the circadian repertoire. Circadian reprogramming in response to chronic inflammation has implications for inflammatory co-morbidities and time-of-day therapeutics.

This paper investigates the meaning of a specific intonation contour called linear lengthening intonation (LLI), which is found in the northern Australian language Iwaidja. Using an experimental field work approach, we analysed approximately 4000 utterances. We demonstrate that the semantics of LLI is broadly event-quantificational as well as temporally scalar. LLI imposes aspectual selectional restrictions on the verbs it combines with (they must be durative, i.e., cannot describe ‘punctual’, atomic events), and requires the event description effected by said verbs to exceed a contextually determined relative scalar meaning. Iwaidja differs from other northern Australian languages with similar intonation patterns in that it does not seem to have any argument NP-related incremental or event scalar meaning. This suggests that LLI is a decidedly grammatical, language-specific device and not a purely iconic kind of expression (even though it also possibly has an iconic dimension).

Severe burn injury leads to a cascade of local and systemic immune responses that trigger an extreme state of immune dysfunction, leaving the patient highly susceptible to acute and chronic infection. When combined with inhalation injury, burn patients have higher mortality and a greater chance of developing secondary respiratory complications including infection. No animal model of combined burn and inhalation injury (B+I) exists that accurately mirrors the human clinical picture, nor are there any effective immunotherapies or predictive models of the risk of immune dysfunction. Our earlier work showed that the mechanistic/mammalian target of rapamycin (mTOR) pathway is activated early after burn injury, and its chemical blockade at injury reduced subsequent chronic bacterial susceptibility. It is unclear if mTOR plays a role in the exacerbated immune dysfunction seen after B+I injury. We aimed to: (1) characterize a novel murine model of B+I injury, and (2) investigate the role of mTOR in the immune response after B+I injury. Pulmonary and systemic immune responses to B+I were characterized in the absence or presence of mTOR inhibition at the time of injury. Data describe a murine model of B+I with inhalation-specific immune phenotypes and implicate mTOR in the acute immune dysfunction observed.

Burn patients are subject to significant acute immune and metabolic dysfunction. Concomitant inhalation injury increases mortality by 20%. In order to identify specific immune and metabolic signaling pathways in burn (B), inhalation (I), and combined burn-inhalation (BI) injury, unbiased nanoString multiplex technology was used to investigate gene expression within peripheral blood mononuclear cells (PBMCs) from burn patients, with and without inhalation injury. PBMCs were collected from 36 injured patients and 12 healthy, non-burned controls within 72 h of injury. mRNA was isolated and hybridized with probes for 1342 genes related to general immunology and cellular metabolism. From these specific gene patterns, specific cellular perturbations and signaling pathways were inferred using robust bioinformatic tools. In both B and BI injuries, elements of mTOR, PPARγ, TLR, and NF-kB signaling pathways were significantly altered within PBMC after injury compared to PBMC from the healthy control group. Using linear regression modeling, (1) DEPTOR, LAMTOR5, PPARγ, and RPTOR significantly correlated with patient BMI; (2) RPTOR significantly correlated with patient length of stay, and (3) MRC1 significantly correlated with the eventual risk of patient mortality. Identification of mediators of this immunometabolic response that can act as biomarkers and/or therapeutic targets could ultimately aid the management of burn patients.

One of the main characteristics of human languages is that they are subject to fundamental changes over time. However, because of the long transitional periods involved, the internal dynamics of such changes are typically inaccessible. Here, we present a new approach to examining language change via its connection to language comprehension. By means of an EEG experiment on Icelandic, a prominent current example of a language in transition, we show that the neurophysiological responses of native speakers already reflect projected changes that are not yet apparent in their overt behavior. Neurocognitive measures thus offer a means of predicting, rather than only retracing, language change.

Efficient mitochondrial function is required in tissues with high energy demand such as the heart, and mitochondrial dysfunction is associated with cardiovascular disease. Expression of mitochondrial proteins is tightly regulated in response to internal and external stimuli. Here we identify a novel mechanism regulating mitochondrial content and function, through BUD23-dependent ribosome generation. BUD23 was required for ribosome maturation, normal 18S/28S stoichiometry and modulated the translation of mitochondrial transcripts in human A549 cells. Deletion of Bud23 in murine cardiomyocytes reduced mitochondrial content and function, leading to severe cardiomyopathy and death. We discovered that BUD23 selectively promotes ribosomal interaction with low GC-content 5’UTRs. Taken together we identify a critical role for BUD23 in bioenergetics gene expression, by promoting efficient translation of mRNA transcripts with low 5’UTR GC content. BUD23 emerges as essential to mouse development, and to postnatal cardiac function.

Genetic methods are useful to test whether risk factors are causal for or consequence of disease. Here, Zhu et al. develop a generalized summary-based Mendelian Randomization (GSMR) method which uses summary-level data from GWAS to test for causal associations of health risk factors with common diseases.

Severe burn injury is a devastating form of trauma that results in persistent immune dysfunction with associated morbidity and mortality. The underlying drivers of this immune dysfunction remain elusive, and there are no prognostic markers to identify at-risk patients. Extracellular vesicles (EVs) are emerging as drivers of immune dysfunction as well as biomarkers. We investigated if EVs after burn injury promote macrophage activation and assessed if EV contents can predict length of hospital stay. EVs isolated early from mice that received a 20% total body surface area (TBSA) burn promoted proinflammatory responses in cultured splenic macrophages. Unbiased LC-MS/MS proteomic analysis of early EVs (

Weather forecasting relies on the use of numerical weather prediction (NWP) models, whose resolution is informed by the available computational resources. The models resolve large scale processes, while subgrid processes are parametrized. One of the processes that is parametrized is turbulence which is represented in planetary boundary layer (PBL) schemes. In this study, we evaluate the sensitivity of heavy rainfall events over Zambia to four different PBL schemes in the Weather Research and Forecasting (WRF) model using a parent domain with a 9 km grid length and a 3 km grid spacing child domain. The four PBL schemes are the Yonsei University (YSU), nonlocal first-order medium-range forecasting (MRF), University of Washington (UW) and Mellor–Yamada–Nakanishi–Niino (MYNN) schemes. Simulations were done for three case studies of extreme rainfall on 17 December 2016, 21 January 2017 and 17 April 2019. The use of YSU produced the highest rainfall peaks across all three cases; however, it produced performance statistics similar to UW that are higher than those of the two other schemes. These statistics are not maintained when adjusted for random hits, indicating that the extra events are mainly random rather than being skillfully placed. UW simulated the lowest PBL height, while MRF produced the highest PBL height, but this was not matched by the temperature simulation. The YSU and MYNN PBL heights were intermediate at the time of the peak; however, MYNN is associated with a slower decay and higher PBL heights at night. WRF underestimated the maximum temperature during all cases and for all PBL schemes, with a larger bias in the MYNN scheme. We support further use of the YSU scheme, which is the scheme selected for the tropical suite in WRF. The different simulations were in some respects more similar to one another than to the available observations. Satellite rainfall estimates and the ERA5 reanalysis showed different rainfall distributions, which indicates a need for more ground observations to assist with studies like this one.

Namibia is considered to be one of the countries that are most vulnerable to climate change due to its generally dry climate and the percentage of its population that rely on subsistence agriculture for their livelihoods. Early-warning systems are an important aspect of adapting to climate change. Weather forecasting relies on the use of numerical weather prediction models and these need to be configured properly. In this study, we investigate the effects of using multi-nests and a convection scheme on the simulation of a heavy rainfall event over the north-western region of Kunene, Namibia. The event, which was associated with a cut-off low system, was short-lived and resulted in over 45 mm of rainfall in one hour. For the multi-nest, a 9 km grid-length parent domain is nested within the Global Forecast System (GFS) simulations, which in turn forces a 3 km grid spacing child domain. A different set of simulations are produced using a single nest of 3 km grid spacing, nested directly inside the GFS data. The simulations are produced with the convection scheme switched on and off. The impact of a single versus multi-nest is found to be small in general, with slight differences in the location of high rainfall intensity. Switching off the convection schemes results in high rainfall intensity and increased detail in the simulations, including when a grid spacing of 9 km is used. Using a grid spacing of 3 km with the convection scheme on, results in a loss of detail in the simulations as well as lower rainfall amounts. The study shows a need for different configurations to be tested before an optimum configuration can be selected for operational forecasting. We recommend further tests with different synoptic forcing and convection schemes to be conducted to identify a suitable configuration for Namibia.

Modulating immune responses to sepsis and trauma remain one of the most difficult challenges in modern medicine. Large burn injuries (LBI) are a severe form of trauma associated with sepsis, immune impairment, and mortality. Immune dysfunction after LBI is complex, involving both enhanced and impaired immune activation. The release of Damage-Associated Molecular Patterns (DAMPs), such as HMGB1, and cytokines (e.g. IL-1β) creates an environment of immune dysfunction often leading to end organ failure and death. Both HMGB1 and IL-1β have been found to play critical roles in sepsis and post-burn immune dysfunction. HMGB1 and IL-1β have been shown previously to form potent complexes in vitro. We recently identified the presence of HMGB1/IL-1β heterocomplexes in human tissue. We now find HMGB1/IL-1β complexes in human and mouse plasma, and identify a synergistic role of HMGB1/IL-1β complexes in post-burn immune dysfunction. In both humans and mice, we found that HMGB1 was enriched in plasma microvesicles (MVs) after LBI. HMGB1 was found form complexes with IL-1β. Using flow cytometry of mouse plasma MVs, we identified an increase in an HMGB1+/IL-1β+ MVs. Using co-IP, HMGB1 was found to bind the pro-form of IL-1β in mouse and human plasma. Pro-IL-1β, which is traditionally considered inactive, became active when complexed with HMGB1. Human THP-1 monocytes treated with HMGB1-pro-IL-1β complexes showed increased transcription of LBI associated cytokines IL-6 and IFNβ along with suppression of iNOS, mimicking findings associated with LBI. These findings identify that HMGB1/IL-1β complexes released after burn injuries can modulate immune responses, and microvesicles are identified as a novel reservoir for these immune mediators. These complexes might serve as novel immune targets for the treatment of systemic immune responses due to LBI or other causes of sepsis.

Chronic coinfections of Staphylococcus aureus and Pseudomonas aeruginosa frequently fail to respond to antibiotic treatment, leading to significant patient morbidity and mortality. Currently, the impact of interspecies interaction on S. aureus antibiotic susceptibility remains poorly understood. In this study, we utilize a panel of P. aeruginosa burn wound and cystic fibrosis (CF) lung isolates to demonstrate that P. aeruginosa alters S. aureus susceptibility to bactericidal antibiotics in a variable, strain-dependent manner and further identify 3 independent interactions responsible for antagonizing or potentiating antibiotic activity against S. aureus. We find that P. aeruginosa LasA endopeptidase potentiates lysis of S. aureus by vancomycin, rhamnolipids facilitate proton-motive force-independent tobramycin uptake, and 2-heptyl-4-hydroxyquinoline N-oxide (HQNO) induces multidrug tolerance in S. aureus through respiratory inhibition and reduction of cellular ATP. We find that the production of each of these factors varies between clinical isolates and corresponds to the capacity of each isolate to alter S. aureus antibiotic susceptibility. Furthermore, we demonstrate that vancomycin treatment of a S. aureus mouse burn infection is potentiated by the presence of a LasA-producing P. aeruginosa population. These findings demonstrate that antibiotic susceptibility is complex and dependent not only upon the genotype of the pathogen being targeted, but also on interactions with other microorganisms in the infection environment. Consideration of these interactions will improve the treatment of polymicrobial infections.

Burn patients suffer from immunological dysfunction for which there are currently no successful interventions. Similar to previous observations, we find that burn shock patients (≥15% Total Burn Surface Area (TBSA) injury) have elevated levels of the innate immune cytokines Interleukin-6 (IL-6) and Monocyte Chemoattractant Protein-1 (MCP-1)/CC-motif Chemokine Ligand 2(CCL2) early after hospital admission (0-48 Hours Post-hospital Admission (HPA). Functional immune assays with patient Peripheral Blood Mononuclear Cells (PBMCs) revealed that burn shock patients (≥15% TBSA) produced elevated levels of MCP-1/CCL2 after innate immune stimulation ex vivo relative to mild burn patients. Interestingly, treatment of patient PBMCs with the Nuclear Factor-Erythroid-2-Related Factor 2 (NRF2) agonist, CDDO-Me(bardoxolone methyl), reduced MCP-1 production but not IL-6 or Interleukin-10 (IL-10) secretion. In enriched monocytes from healthy donors, CDDO-Me(bardoxolone methyl) also reduced LPS-induced MCP1/CCL2 production but did not alter IL-6 or IL-10 secretion. Similar immunomodulatory effects were observed with Compound 7, which activates the NRF2 pathway through a different and non-covalent Mechanism Of Action (MOA). Hence, our findings with CDDO-Me(bardoxolone methyl) and Compound 7 are likely to reflect a generalizable aspect of NRF2 activation. These observed effects were not specific to LPS-induced immune responses, as NRF2 activation also reduced MCP-1/CCL2 production after stimulation with IL-6. Pharmacological NRF2 activation reduced Mcp-1/Ccl2 transcript accumulation without inhibiting either Il-6 or Il-10 transcript levels. Hence, we describe a novel aspect of NRF2 activation that may contribute to the beneficial effects of NRF2 agonists during disease. Our work also demonstrates that the NRF2 pathway is retained and can be modulated to regulate important immunomodulatory functions in burn patient immune cells.

[This corrects the article DOI: 10.1371/journal.pone.0184164.].

Aflatoxins are fungal metabolites that contaminate foods and feeds, causing adverse health effects in humans and animals. This study determined the occurrence of aflatoxins in fish feeds and their potential effects on fish. Eighty-one fish feeds were sampled from 70 farms and 8 feed manufacturing plants in Nyeri, Kenya for aflatoxin analysis using competitive enzyme-linked immunosorbent assay. Fish were sampled from 12 farms for gross and microscopic pathological examination. Eighty-four percent of feeds sampled tested positive for aflatoxins, ranging from 1.8 to 39.7 µg/kg with a mean of 7.0 ± 8.3 µg/kg and the median of 3.6 µg/kg. Fifteen feeds (18.5%) had aflatoxins above the maximum allowable level in Kenya of 10 µg/kg. Homemade and tilapia feeds had significantly higher aflatoxin levels than commercial and trout feeds. Feeds containing maize bran and fish meal had significantly higher aflatoxin levels than those without these ingredients. Five trout farms (41.7%) had fish with swollen abdomens, and enlarged livers with white or yellow nodules, which microscopically had large dark basophilic hepatic cells with hyperchromatic nuclei in irregular cords. In conclusion, aflatoxin contamination of fish feeds is prevalent in Nyeri, and may be the cause of adverse health effects in fish in this region.

Intervertebral disc degeneration is accompanied by elevated levels of inflammatory cytokines that have been implicated in disease etiology and matrix degradation. While the effects of inflammatory stimulation on disc cell metabolism have been well-studied, their effects on cell biophysical properties have not been investigated. The hypothesis of this study is that inflammatory stimulation alters the biomechanical properties of isolated disc cells and volume responses to step osmotic loading. Cells from the nucleus pulposus (NP) of bovine discs were isolated and treated with either lipopolysaccharide (LPS), an inflammatory ligand, or with the recombinant cytokine TNF-α for 24 hours. We measured cellular volume regulation responses to osmotic loading either immediately after stimulation or after a 1 week recovery period from the inflammatory stimuli. Cells from each group were tested under step osmotic loading and the transient volume-response was captured via time-lapse microscopy. Volume-responses were analyzed using mixture theory framework to investigate two biomechanical properties of the cell, the intracellular water content and the hydraulic permeability. Intracellular water content did not vary between treatment groups, but hydraulic permeability increased significantly with inflammatory treatment. In the 1 week recovery group, hydraulic permeability remained elevated relative to the untreated recovery control. Cell radius was also significantly increased both after 24 hours of treatment and after 1 week recovery. A significant linear correlation was observed between hydraulic permeability and cell radius in untreated cells at 24 hours and at 1-week recovery, though not in the inflammatory stimulated groups at either time point. This loss of correlation between cell size and hydraulic permeability suggests that regulation of volume change is disrupted irreversibly due to inflammatory stimulation. Inflammatory treated cells exhibited altered F-actin cytoskeleton expression relative to untreated cells. We also found a significant decrease in the expression of aquaporin-1, the predominant water channel in disc NP cells, with inflammatory stimulation. To our knowledge, this is the first study providing evidence that inflammatory stimulation directly alters the mechanobiology of NP cells. The cellular biophysical changes observed in this study are coincident with documented changes in the extracellular matrix induced by inflammation, and may be important in disease etiology.

Severe trauma renders patients susceptible to infection. In sepsis, defective bacterial clearance has been linked to specific deviations in the innate immune response. We hypothesized that innate immune modulations observed during sepsis also contribute to increased bacterial susceptibility after severe trauma. A well-established murine model of burn injury, used to replicate infection following trauma, showed that wound inoculation with P. aeruginosa quickly spreads systemically. The systemic IL-10/IL-12 axis was skewed after burn injury with infection as indicated by a significant elevation in serum IL-10 and polarization of neutrophils into an anti-inflammatory ("N2"; IL-10(+) IL-12(-)) phenotype. Infection with an attenuated P. aeruginosa strain (ΔCyaB) was cleared better than the wildtype strain and was associated with an increased pro-inflammatory neutrophil ("N1"; IL-10(-)IL-12(+)) response in burn mice. This suggests that neutrophil polarization influences bacterial clearance after burn injury. Administration of a TLR5 agonist, flagellin, after burn injury restored the neutrophil response towards a N1 phenotype resulting in an increased clearance of wildtype P. aeruginosa after wound inoculation. This study details specific alterations in innate cell populations after burn injury that contribute to increased susceptibility to bacterial infection. In addition, for the first time, it identifies neutrophil polarization as a therapeutic target for the reversal of bacterial susceptibility after injury.

Acute lung injury (ALI) is a major factor determining morbidity following burns and inhalational injury. In experimental models, factors potentially contributing to ALI risk include inhalation of toxins directly causing cell damage; inflammation; and infection. However, few studies have been done in humans.We carried out a prospective observational study of patients admitted to the NC Jaycees Burn Center who were intubated and on mechanical ventilation for burns and suspected inhalational injury. Subjects were enrolled over an 8-month period and followed till discharge or death. Serial bronchial washings from clinically-indicated bronchoscopies were collected and analyzed for markers of cell injury and inflammation. These markers were compared with clinical markers of ALI.Forty-three consecutive patients were studied, with a spectrum of burn and inhalation injury severity. Visible soot at initial bronchoscopy and gram negative bacteria in the lower respiratory tract were associated with ALI in univariate analyses. Subsequent multivariate analysis also controlled for % body surface area burns, infection, and inhalation severity. Elevated IL-10 and reduced IL-12p70 in bronchial washings were statistically significantly associated with ALI.Independently of several factors including initial inhalational injury severity, infection, and extent of surface burns, high early levels of IL-10 and low levels of IL-12p70 in the central airways are associated with ALI in patients intubated after acute burn/inhalation injury. Lower airway secretions can be collected serially in critically ill burn/inhalation injury patients and may yield important clues to specific pathophysiologic pathways.