Experimental and modelling evidence for structural crossover in supercritical CO₂

Physics of supercritical state is understood to a much lesser degree compared to subcritical liquids. Carbon dioxide in particular has been intensely studied, yet little is known about the supercritical part of its phase diagram. Here, we combine neutron scattering experiments and molecular dynamics simulations and demonstrate the structural crossover at the Frenkel line. The crossover is seen at pressures as high as 14 times the critical pressure and is evidenced by changes of the main features of the structure factor and pair distribution functions

The Unique Determination of Neuronal Currents in the Brain via Magnetoencephalography

The problem of determining the neuronal current inside the brain from measurements of the induced magnetic field outside the head is discussed under the assumption that the space occupied by the brain is approximately spherical. By inverting the Geselowitz equation, the part of the current which can be reconstructed from the measurements is precisely determined. This actually consists of only certain moments of one of the two functions specifying the tangential part of the current. The other function specifying the tangential part of the current as well as the radial part of the current are completely arbitrary. However, it is also shown that with the assumption of energy minimization, the current can be reconstructed uniquely. A numerical implementation of this unique reconstruction is also presented

ALMA and ROSINA detections of phosphorus-bearing molecules: the interstellar thread between star-forming regions and comets

To understand how Phosphorus-bearing molecules are formed in star-forming regions, we have analysed ALMA observations of PN and PO towards the massive star-forming region AFGL 5142, combined with a new analysis of the data of the comet 67P/Churyumov-Gerasimenko taken with the ROSINA instrument onboard Rosetta. The ALMA maps show that the emission of PN and PO arises from several spots associated with low-velocity gas with narrow linewidths in the cavity walls of a bipolar outflow. PO is more abundant than PN in most of the spots, with the PO/PN ratio increasing as a function of the distance to the protostar. Our data favor a formation scenario in which shocks sputter phosphorus from the surface of dust grains, and gas-phase photochemistry induced by UV photons from the protostar allows efficient formation of the two species in the cavity walls. Our analysis of the ROSINA data has revealed that PO is the main carrier of P in the comet, with PO/PN>10. Since comets may have delivered a significant amount of prebiotic material to the early Earth, this finding suggests that PO could contribute significantly to the phosphorus reservoir during the dawn of our planet. There is evidence that PO was already in the cometary ices prior to the birth of the Sun, so the chemical budget of the comet might be inherited from the natal environment of the Solar System, which is thought to be a stellar cluster including also massive stars

An evaluation of three DoE-guided meta-heuristic-based solution methods for a three-echelon sustainable distribution network

This article evaluates the efficiency of three meta-heuristic optimiser (viz. MOGA-II, MOPSO and NSGA-II)-based solution methods for designing a sustainable three-echelon distribution network. The distribution network employs a bi-objective location-routing model. Due to the mathematically NP-hard nature of the model a multi-disciplinary optimisation commercial platform, modeFRONTIER®, is adopted to utilise the solution methods. The proposed Design of Experiment (DoE)-guided solution methods are of two phased that solve the NP-hard model to attain minimal total costs and total CO2 emission from transportation. Convergence of the optimisers are tested and compared. Ranking of the realistic results are examined using Pareto frontiers and the Technique for Order Preference by Similarity to Ideal Solution approach, followed by determination of the optimal transportation routes. A case of an Irish dairy processing industry’s three-echelon logistics network is considered to validate the solution methods. The results obtained through the proposed methods provide information on open/closed distribution centres (DCs), vehicle routing patterns connecting plants to DCs, open DCs to retailers and retailers to retailers, and number of trucks required in each route to transport the products. It is found that the DoE-guided NSGA-II optimiser based solution is more efficient when compared with the DoE-guided MOGA-II and MOPSO optimiser based solution methods in solving the bi-objective NP-hard three-echelon sustainable model. This efficient solution method enable managers to structure the physical distribution network on the demand side of a logistics network, minimising total cost and total CO2 emission from transportation while satisfying all operational constraints

Cumulative Prognostic Score Predicting Mortality in Patients Older Than 80 Years Admitted to the ICU.

OBJECTIVES: To develop a scoring system model that predicts mortality within 30 days of admission of patients older than 80 years admitted to intensive care units (ICUs). DESIGN: Prospective cohort study. SETTING: A total of 306 ICUs from 24 European countries. PARTICIPANTS: Older adults admitted to European ICUs (N = 3730; median age = 84 years [interquartile range = 81-87 y]; 51.8% male). MEASUREMENTS: Overall, 24 variables available during ICU admission were included as potential predictive variables. Multivariable logistic regression was used to identify independent predictors of 30-day mortality. Model sensitivity, specificity, and accuracy were evaluated with receiver operating characteristic curves. RESULTS: The 30-day-mortality was 1562 (41.9%). In multivariable analysis, these variables were selected as independent predictors of mortality: age, sex, ICU admission diagnosis, Clinical Frailty Scale, Sequential Organ Failure Score, invasive mechanical ventilation, and renal replacement therapy. The discrimination, accuracy, and calibration of the model were good: the area under the curve for a score of 10 or higher was .80, and the Brier score was .18. At a cut point of 10 or higher (75% of all patients), the model predicts 30-day mortality in 91.1% of all patients who die. CONCLUSION: A predictive model of cumulative events predicts 30-day mortality in patients older than 80 years admitted to ICUs. Future studies should include other potential predictor variables including functional status, presence of advance care plans, and assessment of each patient's decision-making capacity

Relationship between the Clinical Frailty Scale and short-term mortality in patients ≥ 80 years old acutely admitted to the ICU: a prospective cohort study.

BACKGROUND: The Clinical Frailty Scale (CFS) is frequently used to measure frailty in critically ill adults. There is wide variation in the approach to analysing the relationship between the CFS score and mortality after admission to the ICU. This study aimed to evaluate the influence of modelling approach on the association between the CFS score and short-term mortality and quantify the prognostic value of frailty in this context. METHODS: We analysed data from two multicentre prospective cohort studies which enrolled intensive care unit patients ≥ 80 years old in 26 countries. The primary outcome was mortality within 30-days from admission to the ICU. Logistic regression models for both ICU and 30-day mortality included the CFS score as either a categorical, continuous or dichotomous variable and were adjusted for patient's age, sex, reason for admission to the ICU, and admission Sequential Organ Failure Assessment score. RESULTS: The median age in the sample of 7487 consecutive patients was 84 years (IQR 81-87). The highest fraction of new prognostic information from frailty in the context of 30-day mortality was observed when the CFS score was treated as either a categorical variable using all original levels of frailty or a nonlinear continuous variable and was equal to 9% using these modelling approaches (p < 0.001). The relationship between the CFS score and mortality was nonlinear (p < 0.01). CONCLUSION: Knowledge about a patient's frailty status adds a substantial amount of new prognostic information at the moment of admission to the ICU. Arbitrary simplification of the CFS score into fewer groups than originally intended leads to a loss of information and should be avoided. Trial registration NCT03134807 (VIP1), NCT03370692 (VIP2)

Sepsis at ICU admission does not decrease 30-day survival in very old patients: a post-hoc analysis of the VIP1 multinational cohort study.

BACKGROUND: The number of intensive care patients aged ≥ 80 years (Very old Intensive Care Patients; VIPs) is growing. VIPs have high mortality and morbidity and the benefits of ICU admission are frequently questioned. Sepsis incidence has risen in recent years and identification of outcomes is of considerable public importance. We aimed to determine whether VIPs admitted for sepsis had different outcomes than those admitted for other acute reasons and identify potential prognostic factors for 30-day survival. RESULTS: This prospective study included VIPs with Sequential Organ Failure Assessment (SOFA) scores ≥ 2 acutely admitted to 307 ICUs in 21 European countries. Of 3869 acutely admitted VIPs, 493 (12.7%) [53.8% male, median age 83 (81-86) years] were admitted for sepsis. Sepsis was defined according to clinical criteria; suspected or demonstrated focus of infection and SOFA score ≥ 2 points. Compared to VIPs admitted for other acute reasons, VIPs admitted for sepsis were younger, had a higher SOFA score (9 vs. 7, p < 0.0001), required more vasoactive drugs [82.2% vs. 55.1%, p < 0.0001] and renal replacement therapies [17.4% vs. 9.9%; p < 0.0001], and had more life-sustaining treatment limitations [37.3% vs. 32.1%; p = 0.02]. Frailty was similar in both groups. Unadjusted 30-day survival was not significantly different between the two groups. After adjustment for age, gender, frailty, and SOFA score, sepsis had no impact on 30-day survival [HR 0.99 (95% CI 0.86-1.15), p = 0.917]. Inverse-probability weight (IPW)-adjusted survival curves for the first 30 days after ICU admission were similar for acute septic and non-septic patients [HR: 1.00 (95% CI 0.87-1.17), p = 0.95]. A matched-pair analysis in which patients with sepsis were matched with two control patients of the same gender with the same age, SOFA score, and level of frailty was also performed. A Cox proportional hazard regression model stratified on the matched pairs showed that 30-day survival was similar in both groups [57.2% (95% CI 52.7-60.7) vs. 57.1% (95% CI 53.7-60.1), p = 0.85]. CONCLUSIONS: After adjusting for organ dysfunction, sepsis at admission was not independently associated with decreased 30-day survival in this multinational study of 3869 VIPs. Age, frailty, and SOFA score were independently associated with survival

Bi-allelic genetic variants in the translational GTPases GTPBP1 and GTPBP2 cause a distinct identical neurodevelopmental syndrome.

The homologous genes GTPBP1 and GTPBP2 encode GTP-binding proteins 1 and 2, which are involved in ribosomal homeostasis. Pathogenic variants in GTPBP2 were recently shown to be an ultra-rare cause of neurodegenerative or neurodevelopmental disorders (NDDs). Until now, no human phenotype has been linked to GTPBP1. Here, we describe individuals carrying bi-allelic GTPBP1 variants that display an identical phenotype with GTPBP2 and characterize the overall spectrum of GTP-binding protein (1/2)-related disorders. In this study, 20 individuals from 16 families with distinct NDDs and syndromic facial features were investigated by whole-exome (WES) or whole-genome (WGS) sequencing. To assess the functional impact of the identified genetic variants, semi-quantitative PCR, western blot, and ribosome profiling assays were performed in fibroblasts from affected individuals. We also investigated the effect of reducing expression of CG2017, an ortholog of human GTPBP1/2, in the fruit fly Drosophila melanogaster. Individuals with bi-allelic GTPBP1 or GTPBP2 variants presented with microcephaly, profound neurodevelopmental impairment, pathognomonic craniofacial features, and ectodermal defects. Abnormal vision and/or hearing, progressive spasticity, choreoathetoid movements, refractory epilepsy, and brain atrophy were part of the core phenotype of this syndrome. Cell line studies identified a loss-of-function (LoF) impact of the disease-associated variants but no significant abnormalities on ribosome profiling. Reduced expression of CG2017 isoforms was associated with locomotor impairment in Drosophila. In conclusion, bi-allelic GTPBP1 and GTPBP2 LoF variants cause an identical, distinct neurodevelopmental syndrome. Mutant CG2017 knockout flies display motor impairment, highlighting the conserved role for GTP-binding proteins in CNS development across species