324139 research outputs found
Sort by
Severe community-acquired pneumonia: an integral approach
Get PDFBackground: Severe community-acquired pneumonia represents the most critical manifestation of pneumonia acquired outside the hospital and remains a major cause of intensive care admission and death worldwide. It is frequently complicated by acute respiratory failure, circulatory shock, and multiple organ dysfunction, with mortality commonly exceeding 25–40%. Despite progress in vaccination programmes, microbiological diagnostics, and critical care support, major uncertainties persist regarding early recognition, pathogen identification, antimicrobial selection and duration, management of co-infections, and assessment of treatment response. These challenges are amplified by increasing host heterogeneity and antimicrobial resistance. Main body: Contemporary epidemiological studies consistently demonstrate that mortality in severe community–acquired pneumonia is closely linked to the severity of organ dysfunction rather than to pulmonary involvement alone. In response, the recent international guideline definitions incorporate both respiratory and systemic criteria to standardise identification and guide early triage. However, these frameworks also reveal substantial variability related to host factors that influence clinical presentation, microbiological findings, and outcomes. Advanced age, sex, chronic cardiopulmonary disease, diabetes, frailty, and prior healthcare exposure modify risk, while immunocompromised populations—including transplant recipients, patients with malignancy, individuals receiving immunomodulatory therapies, and people living with Human Immunodeficiency Virus in resource-limited settings—face distinct diagnostic and therapeutic challenges. Accurate microbiological diagnosis remains difficult, with mixed or unidentified infections frequently encountered. Structured respiratory sampling and molecular diagnostic techniques, particularly lower respiratory tract multiplex polymerase chain reaction panels, have improved pathogen detection and support earlier optimisation of antimicrobial therapy. Biomarkers such as procalcitonin and C-reactive protein provide complementary information on disease trajectory and response to treatment, enabling more confident reassessment and earlier discontinuation of antibiotics when aligned with clinical improvement. Severity stratification using combined clinical scores, radiological extent, and laboratory markers refines prognostication and informs treatment intensity. Empiric antimicrobial therapy should be initiated promptly and individualised according to patient-specific risk factors for resistant pathogens, with systematic reassessment within 24–48 h. Adjunctive strategies, including advanced respiratory and haemodynamic support, corticosteroids in selected inflammatory phenotypes, and emerging host-directed therapies such as intravenous immunoglobulins, form part of a personalised management approach. Conclusions: An integrated, multidisciplinary strategy that links early recognition, diagnostic precision, severity assessment, and personalised therapy offers a coherent pathway to improve outcomes and promote responsible antimicrobial use in severe community-acquired pneumonia
An Experimental and Numerical Investigation into Compressor Casing Heat Shield Effectiveness †
Get PDFAn investigation was conducted into the effectiveness of heat shields in an aero-engine compressor casing to slow down thermal time constants. The investigation used a combination of experimental measurements from a full-size compressor casing rig, combined with numerical analysis using CFD and thermal modelling. Experiments were performed on a compressor casing both with and without heat shielding in order to determine the heat shield effectiveness. Temperature measurements were taken throughout the casing in order to determine the thermal time constants. The experimental data was then used to validate a thermal model and CFD simulations of the compressor casing. The modelling allowed the heat transfer coefficients in the compressor casing to be determined from the experimentally measured time constants. It was found that the heat shields gave an increase in thermal time constant at each measured location. With a doubling in the time constant at some locations compared to the unshielded case. It was also found that the heat shields need to be fully sealed, as leakage flows significantly reduce their effectiveness
Accounting for the Opportunity Cost of Children's Time in Economic Evaluation: Challenges and Frequently Asked Questions
Get PDFEconomic evaluations carried out from a societal perspective ought to account for the opportunity cost of a range of resources, including those committed by care recipients. People's time is such a resource: it is limited, valuable and it has an opportunity cost that should be reflected in cost calculations. Yet, when it comes to children and young people (CYP), there are few suggestions on how to value their time and include it in economic evaluations. Despite repeated calls for research, this remains a persistent gap in our methodology “playbook”. In this paper, we look at the topic by bringing together seminal literature and recent research findings. We discuss key uncertainties that need to be resolved for the topic to move forwards, outline challenges and “frequently asked questions”, offer our views on possible answers and solutions, and sketch out a roadmap for future research
Bars in low-density environments rotate faster than bars in dense regions
Get PDFDoes the environment of a galaxy directly influence the kinematics of its bar? We present observational evidence that bars in high-density environments exhibit significantly slower rotation rates than bars in low-density environments. Galactic bars are central, extended structures composed of stars, dust and gas, present in approximately 30–70 per cent of luminous spiral galaxies in the local Universe. Recent simulation studies have suggested that the environment can influence the bar rotation rate, , which is used to classify bars as either fast () or slow (). We use estimates of obtained with the Tremaine–Weinberg method applied to Integral Field Unit spectroscopy from Mapping Nearby Galaxies at Apache Point Observatory and Calar Alto Legacy Integral Field Area. After cross-matching these with the projected neighbour density, , we retain 286 galaxies. The analysis reveals that bars in high-density environments are significantly slower (median ) compared to bars in low-density environments (median ); Anderson–Darling p-value of (). This study marks the first empirical test of the hypothesis that fast bars are formed by global instabilities in isolated galaxies, while slow bars are triggered by tidal interactions in dense environments, in agreement with predictions from numerous N-body simulations. Future studies would benefit from a larger sample of galaxies with reliable Integral Field Unit data, required to measure bar rotation rates. Specifically, more data are necessary to study the environmental influence on bar formation within dense settings (i.e. groups, clusters and filaments)
Venture capital as male-lens investing
Get PDFVenture capital (VC) is fuelling the boom in artificial intelligence (AI). Yet analysis of a UK dataset reveals that VC is dominated by men, both as investors and the AI start-ups they fund. Gender disparities are identified in VC decision-makers, the composition of founders and the average capital raised by predominantly male, compared to female, teams. This is particularly pronounced in AI software start-ups, the sector that attracts most investment. Whether and how this gender gap shapes the innovation process itself is a further question explored here. Drawing on feminist science and technology studies, we argue that the homogeneity of the VC ecosystem is key to perpetuating the gender gap in innovation. On this basis, we conceptualise venture capital as effectively a form of ‘male-lens investing’, illustrating the limitations of the male-dominated and profit-driven VC investment model. We believe this theoretical framing contributes to contextualising debates about the need for inclusive innovation systems
Susceptibility to the Neonicotinoid Pesticide Imidacloprid Is Linked to Life History Regulation in Honey Bees ( Apis mellifera L.)
Get PDFThe Western honey bee ( Apis mellifera ) is a globally important pollinator. Its health in natural and managed populations is compromised by numerous factors, including pesticides. Neonicotinoid pesticides are widely used even though they can cause a variety of detrimental effects. Exposure can disrupt the complex life history regulation of worker honey bees and induce precocious foraging and premature death. However, honey bee variation in neonicotinoid susceptibility and underlying mechanisms are poorly understood. We hypothesised that neonicotinoid susceptibility and life history of worker honey bees are innately linked through constitutive patterns of gene expression. We confirmed the relation between worker survival of an acute exposure to the neonicotinoid imidacloprid and the inherent rate of the workers' most fundamental life history transition from in‐hive tasks to initiate foraging in a colony‐level experiment. To investigate the underlying mechanisms, we also compared the whole‐body transcriptomes of young nurses, young foragers, old nurses, and old foragers between bees from colony sources with low versus high imidacloprid susceptibility that were raised in a common single cohort colony environment. These comparisons identified age‐ and behaviour‐related transcriptome changes that are consistent with current models of the life history regulation of honey bee workers but also indicated that age itself has a profound effect on the whole‐body transcriptome. Importantly, hundreds of gene expression changes distinguished honey bees of low and high imidacloprid susceptibility, largely in an age‐ and caste‐specific manner with the most significant biological functions ranging from stress responses and protein homeostasis to apoptosis. General age and behavioural effects on the overall transcriptome correlated with each other, but the transcriptome differences according to imidacloprid susceptibility correlated with the age‐ and behaviour‐related gene expression changes in an age‐specific manner. However, significant directional overlap in differentially expressed genes from low and high imidacloprid susceptible bees existed among age and behavioural groups. Notably, three genes of known function differed consistently between bees of low and high imidacloprid susceptibility: A chitinase potentially providing structural resilience to pesticides, a potentially detoxifying cytochrome P450, and the vitellogenin receptor with putative functions in life history regulation and stress resistance in worker honey bees. These genes provide prime candidates for studying imidacloprid resistance in honey bees and other insects, as well as providing potential mechanistic links between pesticide effects and life history regulation
Systematic analyses of lipid mobilization by human lipid transfer proteins
Get PDFLipid transfer proteins (LTPs) maintain the specialized lipid compositions of organellar membranes1, 2. In humans, many LTPs are implicated in diseases3, but the cargo and auxiliary lipids that facilitate the transfer of the majority of LTPs remain unknown. Here we combined biochemical, lipidomic and computational methods to systematically characterize LTP–lipid complexes4 and measure how LTP gains of function affect cellular lipidomes. We identified bound lipids for around half of the hundreds of LTPs that we analysed, confirming known ligands and identifying new ones across most LTP families. Gains in LTP function affected the cellular abundance of both their known and newly identified lipid ligands, indicating comparable functional relevance of the two ligand sets. Using structural bioinformatics, we characterized mechanisms that contribute to lipid selectivity and identified preferences based on headgroup or acyl chain. We demonstrate some basic principles of how LTPs mobilize their ligands. They commonly interact with several classes of lipids and exhibit broad but selective preference for particular headgroups and for lipid species with shorter acyl chains that contain one or two unsaturated carbons, suggesting that only subsets of lipid species are efficiently mobilized. The datasets represent a resource for further analysis in different cell types and states, such as those associated with pathologies
Modeling partially ionized dense plasma using wavepacket molecular dynamics
No full textWe develop a wave packet molecular dynamics framework for modeling the structural properties of partially-ionized dense plasmas, based on a chemical model that explicitly includes bound state wavefunctions. Using hydrogen as a representative system, we compute self-consistent charge state distributions through free energy minimization, following the approach of Plummer et al. [Phys. Rev. E 111, 015204 (2025)]. This enables a direct comparison of static equilibrium properties with path integral Monte Carlo data, facilitating an evaluation of the model’s underlying approximations and its ability to capture the complex interplay between ionization and structure in dense plasma environments
JADES: the chemical enrichment pattern of distant galaxies – α enhancement, silicon depletion, and iron enhancement
Get PDFWe present gas-phase abundances of carbon (C), -elements (O, Ne, Si, and Ar), and iron (Fe) obtained from stacked spectra of high-z star-forming galaxies with the deep Near Infrared Spectrograph medium-resolution data from the James Webb Space Telescope Advanced Deep Extragalactic Survey. Our 564 sources at –7 have a median stellar mass of and a median star-formation rate of , placing them close to the star-formation main sequence. We find that the stacked spectrum of all our 564 sources has relatively low , moderate , and low values at a low gas-phase metallicity of (), suggesting dominant yields of core-collapse supernovae evolved from massive stars. The detection of a weak [Si iii] emission line in our stacked spectrum provides a silicon-to-oxygen abundance ratio of , which is lower than that of stars in the Milky Way disc and lower than expected by chemical evolution models, suggesting silicon depletion on to dust grains. Likewise, this Si/O value is lower than that we newly derive for two individual galaxies (GN-z11 and RXCJ2248) with negligible dust attenuation. By performing spectral stacking in bins of , star-formation rate (SFR), specific SFR (sSFR), and ultraviolet continuum slope , we identify [Fe iii] line detections in the high-sSFR bin and the blue- bin, both of which exhibit supersolar Fe/O ratios, while their C/O, Ar/O, and Si/O ratios are comparable to those of the all-sources stack. Our findings support a chemically young gas composition with rapid dust depletion in the general population of high-z star-forming galaxies, while raising the possibility of anomalous, selective Fe/O enhancement at the very early epoch of star formation