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Effectiveness of drug interventions to prevent delirium after surgery for older adults: systematic review and network meta-analysis of randomised controlled trials
Get PDFObjective: To identify which drugs are effective at preventing delirium after surgery in adults over 60 years of age and estimate the effects on morbidity and mortality. Design: Systematic review and network meta-analysis. Data sources: Embase, Medline, and Cochrane Library up to 4 March 2024. Eligibility criteria: Randomised controlled trials with administration of one or more drugs for the prevention of delirium after surgery requiring general or regional anaesthesia that recruited participants at least 60 years old and used a validated delirium assessment tool to measure the outcome. Surgery under local anaesthesia only, preoperative mechanical ventilation, and studies of interventions to treat delirium were excluded. Data extraction and synthesis: Assessors masked to each other’s decisions screened studies, extracted data, and assessed risk of bias and quality of evidence in duplicate by using the Cochrane risk of bias tool version 2 and the CINeMA tool. Bayesian arm based network meta-analysis was used to compare interventions. Results: 158 trials were identified with 41 084 participants comparing 52 drug interventions. Seventeen trials were rated as being at high risk of bias. The overall risk of delirium after surgery was 14.5% (n=5957). Dexmedetomidine (odds ratio 0.46, 95% credible interval 0.36 to 0.57), corticosteroids (0.53, 0.31 to 0.87), melatonin receptor agonists (0.54, 0.34 to 0.85), parecoxib (0.34, 0.16 to 0.74), olanzapine (0.27, 0.07 to 0.94), and intranasal insulin (0.13, 0.04 to 0.34) were the most effective interventions at preventing delirium in trials not at high risk of bias. Only corticosteroids reduced the severity of delirium (mean difference −2.42 (95% credible interval −4.72 to −0.12) Memorial Delirium Assessment Scale points). Most interventions had no effect on length of stay, mortality, cognition, or quality of life. Hypotension and bradycardia were more common with dexmedetomidine, but postoperative nausea and vomiting were reduced. Postoperative infection rates were not increased by corticosteroids. Conclusions: Dexmedetomidine is effective in the prevention of postoperative delirium. This finding remains after exclusion of studies at high risk of bias. Corticosteroids, melatonin receptor agonists, parecoxib, intranasal insulin, and olanzapine have potential benefit, although evidence is of moderate to very low quality. Evidence synthesis in this area is complicated by inadequate trial registration practices and incomplete adoption of core outcome sets. Systematic review registration: PROSPERO CRD42023488337
Exploring the quasar disc–wind–jet connection with LoTSS and SDSS
Get PDFWe investigate the relationship between disc winds, radio jets, accretion rates, and black hole masses of a sample of 100 k quasars at z 2. Combining spectra from the 17th data release of the Sloan Digital Sky Survey (SDSS) with radio fluxes from the 2nd data release of the Low Frequency ARray (LOFAR) Two-Meter Sky Survey (LoTSS), we statistically characterize a radio-loud and radio-quiet population using a two-component Gaussian Mixture model, and perform population matching in black hole mass and Eddington fraction. We determine how the fraction of radio-loud sources changes across this parameter space, finding that jets are most efficiently produced in quasars with either a very massive central black hole () or one that is rapidly accreting (). We also show that there are differences in the blueshift of the 1549 Å line and the equivalent width of the 1640 Å line in radio loud and radio-quiet quasars that persist even after accounting for differences in the mass and accretion rate of the central black hole. Generally, we find an anticorrelation between the inferred presence of disc winds and jets, which we suggest is mediated by differences in the quasars’ spectral energy distributions. The latter result is shown through the close coupling between tracers of wind kinematics and the ionizing flux – which holds for both radio-loud and radio-quiet sources, despite differences between their emission line properties – and is hinted at by a different Baldwin effect in the two populations
Novel Physics of Escaping Secondary Atmospheres May Shape the Cosmic Shoreline
Get PDFRecent James Webb Space Telescope observations of cool, rocky exoplanets reveal a probable lack of thick atmospheres, suggesting the prevalent escape of the “secondary” atmospheres formed after losing primordial hydrogen. Yet, simulations indicate that the hydrodynamic escape of secondary atmospheres, composed of nitrogen and carbon dioxide, requires intense fluxes of ionizing radiation (X-ray and extreme ultraviolet (XUV)) to overcome the effects of high molecular weight and efficient line cooling. This transonic outflow of hot, ionized metals (not hydrogen) presents a novel astrophysical regime ripe for exploration. We introduce an analytic framework to determine which planets retain or lose their atmospheres, positioning them on either side of the cosmic shoreline. We model the radial structure of escaping atmospheres as polytropic expansions—power-law relationships between density and temperature driven by local XUV heating. Our approach diagnoses line cooling with a three-level atom model and incorporates how ion–electron interactions reduce the mean molecular weight. Crucially, hydrodynamic escape onsets for a threshold XUV flux depend upon the atmosphere’s gravitational binding. The ensuing escape rates either scale linearly with XUV flux when weakly ionized (energy limited) or are controlled by a collisional–radiative thermostat when strongly ionized. Thus, airlessness is determined by whether the XUV flux surpasses the critical threshold during the star’s active periods, accounting for expendable primordial hydrogen and revival by volcanism. We explore atmospheric escape from the young Sun Mars and Earth, LHS 1140 b and c, and TRAPPIST-1 b. Our modeling characterizes the bottleneck of atmospheric loss on the occurrence of observable Earth-like habitats and offers analytic tools for future studies
Empirically assessing corporate adaptation and resilience disclosure using AI
Get PDFThe extent to which firms are adapting and building resilience to environmental change is crucial information for financial institutions, regulators and governments. While corporates’ physical climate risk exposure of their assets to environmental change can be calculated using models, additional information is needed to evaluate their vulnerability to physical climate change, how well they are adapting and broader alignment with societal adaptation and resilience (A&R) goals. This paper empirically evaluates the extent of A&R-related information in current corporate sustainability reports to provide such insights. We build on established sustainability disclosure frameworks and develop an A&R disclosure framework that we combine with the latest advances in large language models to assess S&P 500 company sustainability reports. We prove that corporate A&R information in sustainability reports is lacking, particularly around risks, metrics and targets, underlining the need to consider other data sources when assessing firm-level risks and contributions to societal A&R goals
PROthrombin complex concentrate versus fresh frozen Plasma for bleeding in adults undergoing HEart SurgerY (PROPHESY-2 trial): a phase III, randomised control trial in England and Wales
Get PDFBackground: Fresh frozen plasma (FFP) is the standard treatment for severe bleeding following cardiac surgery. Despite increasing use of prothrombin complex concentrate (PCC) for coagulopathic bleeding in preference to FFP in the UK, the evidence comparing FFP versus PCC in this setting is lacking. Hypothesis: In adults who develop severe bleeding, PCC is superior to FFP in reducing a composite of mortality, organ failure, or infection up to 90 days following cardiac surgery, and is more cost-effective. Methods: Phase III pragmatic, multicentre, parallel group, superiority, non-blinded, open-label, two-stage group sequential randomised controlled trial with internal pilot embedded. Participants will be recruited by the research team at up to 20 hospitals in England and Wales. Those who have provided informed consent and who develop bleeding within 24 h of cardiac surgery (elective and urgent procedures) will be randomised to PCC (1500 IU if ≤70 kg or 2000 IU if >70 kg; a maximum of 2 doses) or FFP (4 units if ≤70 kg and 5 units if >70 kg; no maximum dose). Randomisation will be stratified by site and will allocate participants using minimisation, with a 1:1 ratio to receive PCC or FFP. Age (≥70 and <70 years) and planned type of surgery (valve only, major aortic surgery, coronary artery bypass graft + valve, and complex/combined procedure) will be the minimisation factors. The primary outcome is a composite of mortality or new onset of respiratory failure, myocardial injury, renal failure, liver injury, intestinal injury, focal neurological deficit, or infection at 90 days. Secondary outcomes will compare safety (transfusion-related reactions, thrombosis), quality of life, healthcare costs, and cost-effectiveness. A sample size of 496 participants will have a 90% power (with a 5% significance level) to detect a relative risk of 0.7 between the two groups at 90 days. The date of the 1st patient enrolled was 11th February 2025. Discussion: This trial will provide evidence on the clinical/cost-effectiveness of PCC versus FFP in cardiac surgery patients who bleed post-surgery. Its outcome will provide high-quality evidence to inform the management of bleeding following cardiac surgery. Trial registration: ISRCTN 92114384. Registered on 16/04/2024. ISRCTN—ISRCTN92114384: PROthrombin complex concentrate versus fresh frozen Plasma for bleeding in adults undergoing HEart SurgerY (PROPHESY-2 trial
JADES: Rest-frame UV-to-NIR Size Evolution of Massive Quiescent Galaxies from Redshift z = 5 to z = 0.5
Get PDFWe present the UV-to-near-IR (NIR) size evolution of a sample of 161 quiescent galaxies with M* > 1010 M⊙over 0.5 1010.6 M⊙. To constrain the physical mechanisms driving the apparent size evolution, we study the relationship between Re and the formation redshift (zform) of quiescent galaxies. For lower-mass quiescent galaxies, this relationship is broadly consistent with Re∝(1+zform)−1 , in line with the expectation of the progenitor effect. For higher-mass quiescent galaxies, the relationship between Re and zform depends on stellar age. Older quiescent galaxies have a steeper relationship between Re and zform than that expected from the progenitor effect alone, suggesting that mergers and/or post-quenching continuous gas accretion drive additional size growth in very massive systems. We find that the z > 3 quiescent galaxies in our sample are very compact, with mass surface densities Σe ≳ 1010 M⊙ kpc−2, and their Re are possibly even smaller than anticipated from the size evolution measured for lower-redshift quiescent galaxies. Finally, we take a close look at the structure of GS-9209, one of the earliest confirmed massive quiescent galaxies at zspec ∼ 4.7. From UV to NIR, GS-9209 becomes increasingly compact, and its light profile becomes more spheroidal, showing that the color gradient is already present in this earliest massive quiescent galaxy
Spatiotemporal epidemiology, geographic hotspots, and risk factor associations of drug-resistant tuberculosis incidence in Indonesia: a Bayesian hierarchical modelling approach
Get PDFBackground: Indonesia ranks among the countries with the highest burden of drug-resistant tuberculosis (DR-TB), contributing approximately 7.4% of global cases, many of which are likely underdiagnosed. To support targeted public health surveillance and control efforts, this study aimed to characterize the spatiotemporal distribution of DR-TB incidence in Indonesia, identify geographic hotspots, and examine associations with health system and socioeconomic factors. Methods: We conducted a nationwide retrospective analysis using annual DR-TB notification data from 2017 to 2022 across all 514 districts, obtained from the national tuberculosis information system. Multivariable Bayesian spatiotemporal regression models were fitted under alternative likelihood assumptions and space-time random effect structures. Model selection criteria were used to identify the best-fitting models for hotspot detection and estimation of risk factor associations. Results: DR-TB predominantly affected individuals aged 25–54 years, aligning with the working-age population. Hotspots were concentrated in urbanized regions, including the Jabodetabek megacity, Greater Surabaya, and districts in South Sumatra. The best-fitting model identified a protective association between first-line treatment success rates and DR-TB incidence [incidence rate ratio (IRR): 0.508; 95% credible interval (CrI): 0.368–0.702]. In contrast, DR-TB incidence was positively associated with the proportion of the population living below the poverty line (IRR: 1.028; 95% CrI: 1.013–1.044), households with improved sanitation access (IRR: 1.006; 95% CrI: 1.002–1.010), and increased municipal human development index (IRR: 1.068; 95% CrI: 1.049–1.094). Conclusions: DR-TB hotspots were primarily concentrated in urban areas, highlighting the need for targeted interventions. Improving first-line tuberculosis treatment success rates and addressing socioeconomic drivers, such as poverty, are critical for controlling DR-TB. Public health policies should prioritize workplace-based support for improving treatment adherence, provide safeguards for TB patients affected by poverty, and underscore the importance of a multisectoral TB surveillance and control program. Graphical Abstract
The hole argument and Putnam's paradox
No full textWe discuss affinities and differences between (i) the hole argument in general relativity and (ii) Putnam’s model-theoretic argument against metaphysical realism (‘Putnam’s paradox’). Following Pooley (2002), we maintain that the hole argument is not a special case of Putnam’s paradox. This notwithstanding, both of these arguments have been responded to through meta-linguistic means. While van Fraassen (1997) claims that Putnam’s paradox dissolves due to our inability to identify a function mapping our theories to objects in the world independent of our total language, Bradley and Weatherall (2022) maintain that the language of general relativity does not allow for the hole argument to be formulated. We compare these responses and assess the extent to which either is successful, concluding that we find van Fraassen’s argument more persuasive precisely because of the greater generality of Putnam’s paradox
Constraints on primordial non-Gaussianity from Quaia
Get PDFWe analyse the large-scale angular clustering of quasars in the Gaia-unWISE quasar catalog, Quaia, and their cross-correlation with maps of the lensing convergence of the Cosmic Microwave Background (CMB), to constrain the level of primordial non-Gaussianity (PNG). Specifically, we target the scale-dependent bias that would be induced by PNG on biased tracers of the matter inhomogeneities on large scales. The Quaia sample is particularly well suited for this analysis, given the large effective volume covered, and our ability to map out the main potential sources of systematic contamination and mitigate their impact. Using the universality relation to characterise the response of the quasar overdensity to PNG (pϕ = 1), we report constraints on the local-type PNG parameter f NL of f NL = -20.5+19.0 -18.1 (68% C.L.) by combining the quasar auto-correlation and its cross-correlation with CMB lensing in two tomographic redshift bins (or f NL = -28.7+26.1 -24.6 if assuming a lower response for quasars, pϕ = 1.6). The error on f NL can be further improved if the cross-correlation between the tomographic redshift bins is included. Using the CMB lensing cross-correlations alone, we find fNL = -13.8+26.7 -25.0 and fNL = -15.6+42.3 -34.8 for pϕ = 1 and pϕ = 1.6 respectively. These are the tightest constraints on fNL to date from angular clustering statistics and cross-correlations with CMB lensing
Atlantic forest tree enhances photoprotective and thermotolerance in soils contaminated by mining tailings
No full textLarge-scale mining disasters in tropical regions impose long-term pressures on ecosystems by degrading soil fertility and exposing native vegetation to chemical and physical disturbances. This study investigates whether Eugenia florida, a native tree species found in both tailings-impacted and reference areas of the Rio Doce Basin in Brazil, exhibits physiological adjustments that confer resilience to combined edaphic and thermal constraints. We assessed soil properties and 16 physiological traits related to nutrient status, photosynthetic efficiency, photoprotection, and thermal tolerance. Soils in the impacted area exhibited markedly lower organic matter, cation exchange capacity, and nutrient concentrations, along with increased iron concentration. Despite a 10% reduction in nitrogen balance index, plants in the impacted area exhibited 10% more chlorophyll and 19% more flavonoids, indicating compensatory pigment production and enhanced antioxidant capacity. Photosynthetic performance remained stable across environments, but individuals in the impacted area displayed elevated regulated energy dissipation and reduced unregulated energy loss, suggesting efficient photoprotective adjustments. Transient fluorescence analyses revealed intensified excitation fluxes and greater heat dissipation per reaction centre. Thermal thresholds, defined as temperatures causing 15% and 50% reductions in photosynthetic efficiency, were significantly higher in impacted individuals. Multivariate analyses identified excitation flux traits as key predictors of thermal resilience. Physiological function in E. florida is sustained through integrated plastic responses under long-term soil degradation and thermal constraints. Its ability to modulate energy fluxes and antioxidant defences highlights its potential as a candidate species for ecological restoration in tropical regions increasingly affected by human disturbance and climate extremes