Increased Respiratory Drive after Prolonged Isoflurane Sedation : A Retrospective Cohort Study

Low-dose isoflurane stimulates spontaneous breathing. We, therefore, tested the hypothesis that isoflurane compared to propofol sedation for at least 48 h is associated with increased respiratory drive in intensive care patients after sedation stop. All patients in our intensive care unit receiving at least 48 h of isoflurane or propofol sedation in 2019 were included. The primary outcome was increased respiratory drive over 72 h after sedation stop, defined as an arterial carbon dioxide pressure below 35 mmHg and a base excess more than −2 mmol/L. Secondary outcomes were acid–base balance and ventilatory parameters. We analyzed 64 patients, 23 patients sedated with isoflurane and 41 patients sedated with propofol. Patients sedated with isoflurane were about three times as likely to show increased respiratory drive after sedation stop than those sedated with propofol: adjusted risk ratio [95% confidence interval]: 2.9 [1.3, 6.5], p = 0.010. After sedation stop, tidal volumes were significantly greater and arterial carbon dioxide partial pressures were significantly lower, while respiratory rates did not differ in isoflurane versus propofol-sedated patients. In conclusion, prolonged isoflurane use in intensive care patients is associated with increased respiratory drive after sedation stop. Beneficial effects of isoflurane sedation on respiratory drive may, thus, extend beyond the actual period of sedation

Aggression and spatial positioning of kin and non-kin fish in social groups

Group-living animals must share space and resources with group mates, who can be either kin or non-kin, and it is often unclear how competitive or cooperative group members should be. In a group-living cichlid, we show that co-habiting females are less aggressive to their female kin (relative to non-kin) despite living at equivalent distances to one another. This pattern was not detected among co-habiting males, revealing that kin-directed social behavior can differ between the sexes.Group-living animals are faced with the challenge of sharing space and local resources amongst group members who may be either relatives or non-relatives. Individuals may reduce the inclusive fitness costs they incur from competing with relatives by either reducing their levels of aggression toward kin, or by maintaining physical separation between kin. In this field study, we used the group-living cichlid Neolamprologus multifasciatus to examine whether within-group aggression is reduced among group members that are kin, and whether kin occupy different regions of their group's territory to reduce kin competition over space and local resources. We determined the kinship relationships among cohabiting adults via microsatellite genotyping and then combined these with spatial and behavioral analyses of groups in the wild. We found that aggressive contests between group members declined in frequency with spatial separation between their shelters. Female kin did not engage in aggressive contests with one another, whereas non-kin females did, despite the fact these females lived at similar distances from one another on their groups' territories. Contests within male-male and male-female dyads did not clearly correlate with kinship. Non-kin male-male and male-female dyads lived at more variable distances from one another on their territories than their corresponding kin dyads. Together, our study indicates that contests among group members can be mediated by relatedness in a sex-dependent manner. We also suggest that spatial relationships can play an important role in determining the extent to which group members compete with one another

Optimal Design and Operation of Solid Sorbent Direct Air Capture Processes at Varying Ambient Conditions

The economic, environmental, and energetic performance of direct air capture (DAC) processes based on solid sorbents depends significantly on ambient air conditions and the availability of renewable resources. High ambient temperature or low humidity leads to higher energy consumption and lower CO2 productivity; lack of renewable resources may make the direct air capture process not viable. With this work, we investigated how the performance of sorbent-based direct air capture plants varies when changing ambient conditions and how the system should be optimally designed and operated to match the time-dependent variations. To this end, we formulated a new modeling framework, where thermodynamic modeling of adsorption processes is bridged to mixed integer linear optimization via a portable linear model of DAC. The process is based on a vacuum-temperature swing cycle, whose performance was obtained with a rate-based thermodynamic model at varying ambient conditions for an exemplary sorbent representative of different amine-functionalized materials. The optimal design and operation were investigated for (i) a stand-alone DAC system installed at three different geographical locations and (ii) a DAC system embedded in a multi-energy hub aimed at supplying the DAC energy demand from renewable resources. We found that DAC performance is optimal when the process can adjust the operating variables according to the weather profile and when CO2 can be produced flexibly over time, for example, by adopting a buffer storage tank. Other operation strategies are suboptimal but might require less sophisticated control systems. Moreover, the results suggest that capturing costs are significantly smaller in cold and humid conditions. This conclusion holds for both the stand-alone and the integrated DAC systems. However, for the latter, cold and humid conditions are favorable only when abundant renewable energy is available and can be supplied at low costs, for example, via wind farms. These conclusions remain true over a wide range of technical and cost assumptions

Supercritical fluid extraction-supercritical fluid chromatography of saliva: Single-quadrupole mass spectrometry monitoring of caffeine for gastric emptying studies†

Saliva is an attractive sampling matrix for measuring various endogenous and exogeneous substances but requires sample treatment prior to chromatographic analysis. Exploiting supercritical CO2 for both extraction and chromatography simplifies sample preparation, reduces organic solvent consumption, and minimizes exposure to potentially infectious samples, but has not yet been applied to oral fluid. Here, we demonstrate the feasibility and benefits of online supercritical fluid extraction coupled to supercritical fluid chromatography and single-quadrupole mass spectrometry for monitoring the model salivary tracer caffeine. A comparison of 13C- and 32S-labeled internal standards with external standard calibration confirmed the superiority of stable isotope-labeled caffeine over nonanalogous internal standards. As proof of concept, the validated method was applied to saliva from a magnetic resonance imaging study of gastric emptying. After administration of 35 mg caffeine via ice capsule, salivary levels correlated with magnetic resonance imaging data, corroborating caffeine's usefulness as tracer of gastric emptying (R2 = 0.945). In contrast to off-line methods, online quantification required only minute amounts of organic solvents and a single manual operation prior to online bioanalysis of saliva, thus demonstrating the usefulness of CO2-based extraction and separation techniques for potentially infective biomatrices

Supercritical fluid extraction–supercritical fluid chromatography of saliva: Single‐quadrupole mass spectrometry monitoring of caffeine for gastric emptying studies †

Abstract Saliva is an attractive sampling matrix for measuring various endogenous and exogeneous substances but requires sample treatment prior to chromatographic analysis. Exploiting supercritical CO 2 for both extraction and chromatography simplifies sample preparation, reduces organic solvent consumption, and minimizes exposure to potentially infectious samples, but has not yet been applied to oral fluid. Here, we demonstrate the feasibility and benefits of online supercritical fluid extraction coupled to supercritical fluid chromatography and single‐quadrupole mass spectrometry for monitoring the model salivary tracer caffeine. A comparison of 13 C‐ and 32 S‐labeled internal standards with external standard calibration confirmed the superiority of stable isotope‐labeled caffeine over nonanalogous internal standards. As proof of concept, the validated method was applied to saliva from a magnetic resonance imaging study of gastric emptying. After administration of 35 mg caffeine via ice capsule, salivary levels correlated with magnetic resonance imaging data, corroborating caffeine's usefulness as tracer of gastric emptying ( R 2 = 0.945). In contrast to off‐line methods, online quantification required only minute amounts of organic solvents and a single manual operation prior to online bioanalysis of saliva, thus demonstrating the usefulness of CO 2 ‐based extraction and separation techniques for potentially infective biomatrices

Ultracold Dense Samples of Dipolar RbCs Molecules in the Rovibrational and Hyperfine Ground State

We produce ultracold dense trapped samples of Rb87Cs133 molecules in their rovibrational ground state, with full nuclear hyperfine state control, by stimulated Raman adiabatic passage (STIRAP) with efficiencies of 90%. We observe the onset of hyperfine-changing collisions when the magnetic field is ramped so that the molecules are no longer in the hyperfine ground state. A strong quadratic shift of the transition frequencies as a function of applied electric field shows the strongly dipolar character of the RbCs ground-state molecule. Our results open up the prospect of realizing stable bosonic dipolar quantum gases with ultracold molecules

Sequestering by global symmetries in Calabi-Yau string models

We study the possibility of realizing an effective sequestering between visible and hidden sectors in generic heterotic string models, generalizing previous work on orbifold constructions to smooth Calabi-Yau compactifications. In these theories, genuine sequestering is spoiled by interactions mixing chiral multiplets of the two sectors in the effective Kahler potential. These effective interactions however have a specific current-current-like structure and can be interpreted from an M-theory viewpoint as coming from the exchange of heavy vector multiplets. One may then attempt to inhibit the emergence of generic soft scalar masses in the visible sector by postulating a suitable global symmetry in the dynamics of the hidden sector. This mechanism is however not straightforward to implement, because the structure of the effective contact terms and the possible global symmetries is a priori model dependent. To assess whether there is any robust and generic option, we study the full dependence of the Kahler potential on the moduli and the matter fields. This is well known for orbifold models, where it always leads to a symmetric scalar manifold, but much less understood for Calabi-Yau models, where it generically leads to a non-symmetric scalar manifold. We then examine the possibility of an effective sequestering by global symmetries, and argue that whereas for orbifold models this can be put at work rather naturally, for Calabi-Yau models it can only be implemented in rather peculiar circumstances.Comment: 47 pages, no figure

Advancing the 3Rs: innovation, implementation, ethics and society

The 3Rs principle of replacing, reducing and refining the use of animals in science has been gaining widespread support in the international research community and appears in transnational legislation such as the European Directive 2010/63/EU, a number of national legislative frameworks like in Switzerland and the UK, and other rules and guidance in place in countries around the world. At the same time, progress in technical and biomedical research, along with the changing status of animals in many societies, challenges the view of the 3Rs principle as a sufficient and effective approach to the moral challenges set by animal use in research. Given this growing awareness of our moral responsibilities to animals, the aim of this paper is to address the question: Can the 3Rs, as a policy instrument for science and research, still guide the morally acceptable use of animals for scientific purposes, and if so, how? The fact that the increased availability of alternatives to animal models has not correlated inversely with a decrease in the number of animals used in research has led to public and political calls for more radical action. However, a focus on the simple measure of total animal numbers distracts from the need for a more nuanced understanding of how the 3Rs principle can have a genuine influence as a guiding instrument in research and testing. Hence, we focus on three core dimensions of the 3Rs in contemporary research: (1) What scientific innovations are needed to advance the goals of the 3Rs? (2) What can be done to facilitate the implementation of existing and new 3R methods? (3) Do the 3Rs still offer an adequate ethical framework given the increasing social awareness of animal needs and human moral responsibilities? By answering these questions, we will identify core perspectives in the debate over the advancement of the 3Rs

Molecular spectroscopy for ground-state transfer of ultracold RbCs molecules

We perform one- and two-photon high resolution spectroscopy on ultracold samples of RbCs Feshbach molecules with the aim to identify a suitable route for efficient ground-state transfer in the quantum-gas regime to produce quantum gases of dipolar RbCs ground-state molecules. One-photon loss spectroscopy allows us to probe deeply bound rovibrational levels of the mixed excited (A1{\Sigma}+ - b3{\Pi}0) 0+ molecular states. Two-photon dark state spectroscopy connects the initial Feshbach state to the rovibronic ground state. We determine the binding energy of the lowest rovibrational level |v"=0,J"=0> of the X1{\Sigma}+ ground state to be DX 0 = 3811.5755(16) 1/cm, a 300-fold improvement in accuracy with respect to previous data. We are now in the position to perform stimulated two-photon Raman transfer to the rovibronic ground state.Comment: Submitted to PCCP themed issue: Physics and Chemistry of Cold Molecule