Target Plasma Research Articles

Generation of polarized proton beams with gaseous targets from CO2-laser-driven collisionless shock acceleration

We propose obtaining polarized proton beams based on CO2-laser-driven collisionless shock acceleration (CSA) of the pre-polarized HCl gas. By tailoring the density profile of the pre-polarized HCl gas, the intense CO2 laser pulse heats the plasma target and forms a strong shock that reflects the polarized protons to high energy. According to particle-in-cell simulations implemented with the spin dynamics, directional proton beams of several MeV were generated at a total beam polarization of over 80%. Simulations showed that proton spin precession occurred in the azimuthal magnetic fields generated by the Biermann effect and plasma currents. The latter was the main depolarization mechanism in the early stage of shock wave formation. For CSA at CO2 laser intensities around 1017–1018 W/cm2, the proton depolarization was insignificant and the beam polarization purity was preserved. As pre-polarized hydrogen targets were available at gaseous densities in-state-of-art facilities, CSA driven by relatively long wavelength lasers provided a feasible solution for obtaining ultra-fast polarized proton sources.

Optimization of levetiracetam dosing regimen in critically ill patients with augmented renal clearance: a Monte Carlo simulation study

BackgroundLevetiracetam pharmacokinetics is extensively altered in critically ill patients with augmented renal clearance (ARC). Consequently, the dosage regimens commonly used in clinical practice may not be sufficient to achieve target plasma concentrations. The aim of this study is to propose alternative dosage regimens able to achieve target concentrations in this population. Furthermore, the feasibility of the proposed dosing regimens will be discussed from a clinical point of view.MethodsDifferent dosage regimens for levetiracetam were evaluated in critically ill patients with ARC. Monte Carlo simulations were conducted with extended or continuous infusions and/or high drug doses using a previously developed population pharmacokinetic model. To assess the clinical feasibility of the proposed dosages, we carried out a literature search to evaluate the information on toxicity and efficacy of continuous administration or high doses, as well as the post-dilution stability of levetiracetam.ResultsAccording to the simulations, target concentrations in patients with CrCl of 160 or 200 mL/min can be achieved with the 3000 mg daily dose by prolonging the infusion time of levetiracetam. For patients with CrCl of 240 mL/min, it would be necessary to administer doses higher than the maximum recommended. Available evidence suggests that levetiracetam administration in continuous infusion or at higher doses than those approved seems to be safe. It would be desirable to re-examinate the current recommendations about drug stability and to achieve a consensus in this issue.ConclusionsConventional dosage regimens of levetiracetam (500–1500 mg twice daily in a short infusion) do not allow obtaining drug plasma concentrations among the defined target in critically ill patients with ARC. Therefore, new dosing guidelines with specific recommendations for patients in this subpopulation are needed. This study proposes new dosages for levetiracetam, including extended (4 or 6 h) infusions, continuous infusions or the administration of doses higher than the recommended in the summary of product characteristics (> 3000 mg). These new dosage recommendations take into account biopharmaceutical and pharmacokinetic aspects and meet feasibility criteria, which allow them to be transferred to the clinical environment with safety and efficacy. Nevertheless, further clinical studies are needed to confirm these results.

Benefits and Challenges of Advanced Divertor Configurations in DEMO

The divertor design and configuration define the power exhaust capabilities of DEMO, and act as a major design driver. They set a number of requirements on the tokamak layout, including port sizes, poloidal field coil positions, and size of toroidal field coils. It also requires a corresponding configuration of plasma-facing components (PFCs) and a remote handling scheme to be able to handle the cassettes and associated in-vessel components the configuration requires.There is a risk that the baseline ITER-like single-null (SN) divertor configuration cannot meet the PFC technology limits regarding power exhaust while achieving the target plasma performance requirements of DEMO or a future fusion power plant. Alternative magnetic configurations (AMCs) – for example, double-null, snowflake, and super-X – exist and potentially offer mitigation solutions to these risks and a route to achievable power handling in DEMO. However, these options impose significant changes on machine architecture, increase the machine complexity and affect remote handling and plasma physics and so an integrated approach must be taken to assessing the feasibility of these options.This paper describes work carried out to define a set of design limitations that any alternative divertor configuration for DEMO must consider, and assesses the feasibility of integration of a set of potential AMCs for DEMO.

Pharmacokinetics of pimobendan following oral administration to New Zealand White rabbits (Oryctolagus cuniculus).

To determine the pharmacokinetics and potential adverse effects of pimobendan after oral administration in New Zealand White rabbits (Ocytolagus cuniculi). 10 adult sexually intact (5 males and 5 females) rabbits. 2 pilot studies were performed with a pimobendan suspension or oral tablets. Eight rabbits received 7.5 mg of pimobendan (mean 2.08 mg/kg) suspended in a critical care feeding formula. Plasma concentrations of pimobendan and O-demethylpimobendan (ODMP) were measured, and pharmacokinetic parameters were calculated for pimobendan by noncompartmental analysis. Body weight, food and water consumption, mentation, urine, and fecal output were monitored. Mean ± SD maximum concentration following pimobendan administration was 15.7 ± 7.54 ng/mL and was detected at 2.79 ± 1.25 hours. The half-life was 3.54 ± 1.32 hours. Plasma concentrations of pimobendan were detectable for up to 24 hours. The active metabolite, ODMP, was detected in rabbits for 24 to 36 hours. An adverse event occurred following administration of pimobendan in tablet form in 1 pilot study, resulting in death secondary to aspiration. No other adverse events occurred. Plasma concentrations of pimobendan were lower than previously reported for dogs and cats, despite administration of higher doses, and had longer time to maximum concentration and half-life. Based on this study, 2 mg/kg of pimobendan in a critical care feeding formulation should maintain above a target plasma concentration for 12 to 24 hours. However, further studies evaluating multiple-dose administration as well as pharmacodynamic studies and clinical trials in rabbits with congestive heart failure are needed to determine accurate dose and frequency recommendations.

Role of Glycoconjugates and Mammalian Sialidases Involved in Viral Infection and Neural Function

Glycoconjugates are present in various organisms, ranging from animals to viruses. Glycoconjugates are involved in several biologically significant functions, including viral infection and neurotransmission. However, the role of glycoconjugates in virus replication and neural function remains unknown. We discovered that the influenza A virus (IAV) binds to sulfatide, which lacks a sialic acid residue, and that delivering sulfatide combined with newly synthesized IAV hemagglutinin (HA) to the target plasma membrane induces the translocation of viral ribonucleoprotein complexes from the nucleus to the cytoplasm. Molecular species of sialic acid are largely classified as N-acetylneuraminic acid (Neu5Ac) and N-glycolylneuraminic acid (Neu5Gc). We discovered that two amino acids in IAV H3 HA play a critical role in the recognition of Neu5Ac and Neu5Gc. Also, we observed that human parainfluenza virus types 1 (hPIV-1) and 3 (hPIV-3) bind to different forms of gangliosides. These viruses preferentially recognized oligosaccharides containing branched N-acetyllactosaminoglycans with terminal Neu5Acα2-3Gal. Neu5Gcα2-3Gal- and NeuAcα2-6Gal-containing receptors were identified by hPIV-3, but not by hPIV-1. We constructed a novel sialidase fluorescent substrate, 2-benzothiazol-2-yl-phenol derivative-based N-acetylneuraminic acid (BTP3-Neu5Ac), which detects sialidase activity in living mammalian tissues and virus-infected cells expressing viral neuraminidase. We discovered that neural activity-dependent desialylation by sialidase contributes to rat hippocampal memory processing. Using BTP3-Neu5Ac, we developed a rapid and sensitive approach for detecting and isolating drug-resistant influenza viruses. This review summarizes the role of sialylglycoconjugates and sulfatide in virus replication as well as mammalian sialidases involved in neural function and insulin secretion.

Spin-Polarized Particle Beams from Laser-Plasma Based Accelerators

Abstract Current laser-plasma based accelerators are promising options with respect to the acceleration of spin-polarized particle beams. We give an overview over the effects relevant during the acceleration process and more specifically discuss the acceleration of protons via Magnetic Vortex Acceleration (MVA). With the aid of particle-in-cell simulations we show that the length of the density down-ramp at the end of the plasma target affects the final beam quality regarding its collimation. The average spin-polarization of the obtained bunch remains largely robust at about 80% and only decreases for significantly longer ramps.

The SedUROscopy Project: Sedation conducted by nurses supervised by the anaesthetist at a Lithotripsy and Endourology Unit in Spain

AbstractThe increased demand for simple, yet invasive and sometimes painful urological procedures in our unit, coupled with a relative lack of anaesthetists, prompted the search for appropriate safe alternatives to current practice, so to enable efficient, satisfactory, and safe interventions for patients. In response to this need, the Four‐Phase SedUROscopy Project has been developed, a plan in which identified Urology nurses take on a more active role in the anaesthetic procedure at the Lithotripsy and Endourology Unit. The aim of the project is to establish a specific care model that ensures the safety and satisfaction of patients undergoing minor endourological procedures, whilst also optimizing resources and empowering nurses and their practice. The SedUROscopy Project started with the training of five nurses (Phase 1: Theory). Subsequently, one of the nurses then began her practical course (Phase 2: up to 200 sedations). She carried out 90 sedations in patients in preparation for minor procedures. Remifentanil and Propofol were administrated using Target Controlled Infusion (TCI) pumps. The initial target plasma propofol concentration was 2 μg/ml, and the remifentanil one was 1 μg/ml. Doses were adjusted to achieve the right sedation. ECG, pulse oximetry, non‐invasive blood pressure and end‐tidal CO2 were monitored. Up to 10 different procedures were carried out. There were 37 oxygen desaturation events (41%), however they were solved with chin lift manoeuvres and mandibular subluxation (8.88%), use of Guedel tube (21.1%) and manual ventilation (11.1%). The intervention of the anaesthetist was not required in any of the cases, and all the patients involved in the sample were discharged the same day, free of any anaesthetic problem at all (100%). As the surveys indicated, the levels of satisfaction expressed by both patient and staff performing the technique were high (98%). The sedation performed by trained urology nurses using TCI has resulted in a provision of safe and effective procedures. Likewise, the patients' satisfaction was ensured. In conclusion, this model represents an optimal use of resources: not only because just a single anaesthetist could supervise two operation theatres, but also nurses could control the patients pain due to their knowledge of endourological procedures and the sedation technique.

Cross-code comparison of the edge codes SOLPS-ITER, SOLEDGE2D and UEDGE in modelling a low-power scenario in the DTT

As reactor-level nuclear fusion experiments are approaching, a solution to the power exhaust issue in future fusion reactors is still missing. The maximum steady-state heat load that can be exhausted by the present technology is around 10 MW m−2. Different promising strategies aiming at successfully managing the power exhaust in reactor-relevant conditions such that the limit is not exceeded are under investigation, and will be tested in the Divertor Tokamak Test (DTT) experiment. Meanwhile, the design of tokamaks beyond the DTT, e.g. EU-DEMO/ARC, is progressing at a high pace. A strategy to work around the present lack of reactor-relevant data consists of exploiting modelling to reduce the uncertainty in the extrapolation in the design phase. Different simulation tools, with their own capabilities and limitations, can be employed for this purpose. In this work, we compare SOLPS-ITER, SOLEDGE2D and UEDGE, three state-of-the-art edge codes heavily used in power exhaust studies, in modelling the same DTT low-power, pure-deuterium, narrow heat-flux-width scenario. This simplified, although still reactor-relevant, testbed eases the cross-comparison and the interpretation of the code predictions, to identify areas where results differ and develop understanding of the underlying causes. Under the conditions investigated, the codes show encouraging agreement in terms of key parameters at both targets, including peak parallel heat flux (1%–45%), ion temperature (2%–19%), and inner target plasma density (1%–23%) when run with similar input. However, strong disagreement is observed for the remaining quantities, from 30% at outer mid-plane up to a factor 4–5 at the targets. The results primarily reflect limitations of the codes: the SOLPS-ITER plasma mesh not reaching the first wall, SOLEDGE2D not including ion-neutral temperature equilibration, and UEDGE enforcing a common ion-neutral temperature. Potential improvements that could help enhance the accuracy of the code models for future applications are also discussed.

Subcycle terahertz field waveforms clocked by attosecond high-harmonic pulses from relativistic laser plasmas

A high-intensity ultrashort laser pulse interacting with a thin plasma target is shown to couple to plasma electrons, driving electron oscillations within the plasma and making these electrons bounce back and forth between plasma boundaries. Each time these recirculating electrons traverse the plasma boundary, they emit bright subcycle terahertz (THz) field waveforms via laser-driven coherent transition radiation. As a concurrent process, laser-driven electrons near the front surface of the plasma target are accelerated to relativistic velocities to emit high-order harmonics (HHs), giving rise to attosecond pulses of vacuum-ultraviolet radiation. These attosecond pulses are shown to provide a high-precision clock for subcycle THz field waveforms. We demonstrate that the delay time between HH pulses and THz waveforms can be tuned with an attosecond precision by varying the thickness of the plasma target, thus opening an avenue toward HH-pump–THz-probe studies of ultrafast processes on the attosecond time scale with table-top laser sources.

Characterisation and optimisation of targets for plasma wakefield acceleration at SPARC_LAB

One of the most important features of plasma-based accelerators is their compactness because plasma modules can have dimensions of the order of mm , providing very high-accelerating fields up to hundreds of GV . The main challenge regarding this type of acceleration lies in controlling and characterising the plasma itself, which then determines its synchronisation with the particle beam to be accelerated in an external injection stage in the laser wakefield acceleration (LWFA) scheme. This issue has a major influence on the quality of the accelerated bunches. In this work, a complete characterisation and optimisation of plasma targets available at the SPARC_LAB laboratories is presented. Two plasma-based devices are considered: supersonic nozzles for experiments adopting the self-injection scheme of laser wakefield acceleration and plasma capillary discharge for both particle and laser-driven experiments. In the second case, a wide range of plasma channels, gas injection geometries and discharge voltages were extensively investigated as well as studies of the plasma plumes exiting the channels, to control the plasma density ramps. Plasma density measurements were carried out for all the different designed plasma channels using interferometric methods in the case of gas jets, spectroscopic methods in the case of capillaries.

Optimized laser-assisted electron injection into a quasilinear plasma wakefield.

We present an electron injection scheme for plasma wakefield acceleration. The method is based on a recently proposed technique of fast electron generation via laser-solid interaction: a femtosecond laser pulse with the energy of tens of mJ hitting a dense plasma target at 45^{∘} angle expels a well collimated bunch of electrons and accelerates these close to the specular direction up to several MeVs. We study trapping of these fast electrons by a quasilinear wakefield excited by an external beam driver in a surrounding low density plasma. This configuration can be relevant to the AWAKE experiment at CERN. We vary different injection parameters: the phase and angle of injection, the laser pulse energy. An approximate trapping condition is derived for a linear axisymmetric wake. It is used to optimize the trapped charge and is verified by three-dimensional particle-in-cell simulations. It is shown that a quasilinear plasma wave with the accelerating field ∼ 2.5 GV/m can trap electron bunches with ∼ 100 pC charge, ∼60μm transverse normalized emittance and accelerate them to energies of several GeV with the spread ≲ 1% after 10 m..

Divergence gating towards far-field isolated attosecond pulses

Divergence gating, a novel method to generate far-field isolated attosecond pulses (IAPs) through controlling divergences of different pulses, is proposed and realized by relativistic chirped laser–plasma interactions. Utilizing various wavefronts for different cycles of incident chirped lasers, reflected harmonics with minimum divergences are obtained only at the peak cycle when plasma targets are adjusted to proper distances from foci of lasers. Therefore, the corresponding attosecond pulse is isolated in far field due to much slower decay during propagation than others. Confirmed by three-dimensional numerical simulations, millijoule-level sub-50 as IAPs with intensity approaching 1016 W cm−2 (1017–1018 W sr−1) are obtained by our scheme, where low-order harmonics can be preserved.

Evaluation of the anesthetic depth and bispectral index during propofol sequential target-controlled infusion in dogs.

Background and Aim:The use of anesthetic infusions based on pharmacokinetic values associated with anesthetic plan and bispectral index in dogs have not been well-documented in the literature. This study aimed to evaluate the bispectral index (BIS) change based on pre-propofol and establish clinical anesthetic depth changes during propofol sequential target-controlled infusion (STCI) in dogs with a plasma target of 5 μg/mL.Materials and Methods:Twenty healthy male dogs aged 1-3 years and weighing 9.8-44 kg were recruited. These dogs were pre-medicated intramuscularly with methadone (0.2 mg/kg) and acepromazine (0.03 mg/kg). After 30 min, propofol anesthetic induction and maintenance were initiated using STCI according to dog pharmacokinetic (PK) parameters. Subsequently, the target plasma concentration of propofol was set at 5 μg/mL for both anesthetic induction and the 120 min maintenance. Then, TivaTrainer v.9.1 software was used to calculate anesthetic infusion rates in a TCI plasmatic concentration mode using the PKs model optimized by covariates for propofol TCI in dogs. The BIS value was recorded every 5 min from the beginning of induction until the end of anesthesia. Finally, analysis of variance was performed on numerical data using the Friedman test, followed by the Bonferroni adjustment (p<0.05).Results:A statistical difference was observed between the baseline BIS value (T0), with a median value of 84.5 (81-97), and BIS after every 15 min (T15) of inducing anesthesia. Surgical anesthetic depth was also reached in 18 of 20 dogs after 10 min of infusion and in all dogs after 20 min, with a median BIS value of 72 (53-89) at the time of surgical anesthesia depth. Results also showed no BIS variation (p<0.05) between anesthetic moments after anesthetic induction with a substantial amplitude of BIS in the surgical anesthetic depth. Moreover, the maximum depth of anesthesia in all dogs by clinical evaluation was reached after 20 min of anesthesia and then remained stable throughout the anesthetic period.Conclusion:This study suggested that most dogs (90%) attained a surgical depth of anesthesia within 15 min of STCI onset, with a plasma target of 5 μg/mL and no change in anesthetic depth throughout the period anesthesia lasted. Furthermore, median BIS values remained high even after dogs reached the surgical depth of anesthesia, indicating that the comparison of BIS values of dogs and humans should not be considered for classifying anesthetic and hypnotic depths in dogs.

The Dynamics and Nonequilibrium Ionic Composition of a Highly Ionized Plasma Сreated by Interaction of a High-Power Laser-Radiation Pulse with a Cylindrical Plasma Target

The Dynamics and Nonequilibrium Ionic Composition of a Highly Ionized Plasma Сreated by Interaction of a High-Power Laser-Radiation Pulse with a Cylindrical Plasma Target

Enteral feeding tube administration with therapeutic drug monitoring of crushed posaconazole tablets and opened isavuconazonium sulfate capsules.

Isavuconazole and posaconazole are commonly used for both prophylaxis and treatment of invasive fungal infections. These agents are formulated for oral administration as a capsule and delayed release (DR) tablet or suspension, respectively. In patients unable to swallow, alternative means of administration, such as crushing posaconazole DR tablets and opening isavuconazole capsules, may be used to avoid IV administration or use of posaconazole suspension, which often produces subtherapeutic concentrations. To assess the feasibility of achieving target plasma drug concentrations with enteral feeding tube (EFT) administration of crushed posaconazole DR tablets and opened isavuconazole capsules. We retrospectively reviewed pharmacy records to identify patients receiving EFT administration of posaconazole or isavuconazole with concurrent therapeutic drug monitoring from October 2019 to June 2021. Plasma concentrations of either agent as well as clinical outcomes were documented. We identified 37 patients receiving 38 courses of EFT isavuconazole or posaconazole. The majority of patients received primary prophylaxis following lung transplantation (64.9%). Plasma concentrations upon first assessment were therapeutic in the majority of patients (posaconazole 71.5%, isavuconazole 83.3%) with a mean level of 1.61 ± 0.77 mg/L for posaconazole and 2.07 ± 1.1 mg/L for isavuconazole. Of those that were subtherapeutic on initial assessment, all but one subsequently achieved target levels upon dose titration. Standard maintenance doses were used in all isavuconazole and most posaconazole patients. Our case series demonstrates that isavuconazole and posaconazole can be administered via EFT with concurrent therapeutic drug monitoring to achieve target plasma concentrations in the majority of patients.

Management of a human immunodeficiency virus case with discordant antiviral drug resistance profiles in cerebrospinal fluid compared with plasma: a case report

BackgroundHuman immunodeficiency virus-1-associated neurocognitive disorder is a known complication in individuals treated with antiretroviral therapy. Cerebrospinal fluid escape, which is defined as discordant higher cerebrospinal fluid viremia than plasma, may occur in antiretroviral therapy-experienced individuals. Different cerebrospinal fluid versus plasma mutation patterns have been observed in individuals with cerebrospinal fluid escape.Case presentationA 46-year-old adult African male with human immunodeficiency virus-1 infection and acquired immunodeficiency syndrome based on cerebral toxoplasmosis and a chronic hepatitis B virus infection developed cerebrospinal fluid escape. A different human immunodeficiency virus-1 genotypic drug resistance profile was observed in plasma compared with cerebrospinal fluid. Brain biopsy and cerebral magnetic resonance imaging indicated the development of human immunodeficiency virus encephalopathy. A discordant protease inhibitor mutation/wild-type T74PT in plasma but not in cerebrospinal fluid indicated poor central nervous system penetration due to the selective pressure of drug therapy. An intensified antiretroviral therapy regimen including dolutegravir with good central nervous system penetration improved conditions.ConclusionsThis case shows the importance of measuring human immunodeficiency virus drug resistance in cerebrospinal fluid, which might differ from resistance detected in plasma samples and target effective antiretroviral therapy treatment accordingly.

Time-resolved measurement of the free electron and neutral gas line density in a hydrogen theta-pinch plasma target by two-color interferometry

A hydrogen theta-pinch plasma is diagnosed by two-color interferometry to determine the line density of the free electrons and the hydrogen gas. From the ratio of these line densities, the effective ionization can be calculated. The free electron line density and the effective ionization degree are the most essential quantities for the evaluation of the plasma regarding its applicability as a target in context of plasma ion beam interaction to increase the charge state of the ion beam (plasma stripper). The two-color interferometric diagnostic shows that both line densities exhibit a periodic behavior predefined by the periodic current and at the time the free electron line density reaches a local maximum, the hydrogen line density falls to a local minimum. This occurs, because the plasma axially expands from the coil center by evading the radial compression force of the magnetic field, creating an ionizing wave in the residual gas. The theta-pinch was set up in two versions, with one of them using a cylindrical coil and the other using a spherical coil. For the cylindrical version, the best working point regarding the free electron line density and the effective ionization degree is cm−2 and at 20 Pa and 16 kV. In contrast, for the spherical version, lower values of and at 20 Pa and 18 kV were found. Additionally, a new set-up is proposed for optimizing the plasma target regarding the free electron line density and the effective ionization degree, as well as how to maintain them on a sufficient level for several s.

Fluoxetine pharmacokinetics and tissue distribution quantitatively supports a therapeutic role in COVID-19 at a minimum dose of 20 mg per day.

Background. Various in vitro studies have shown fluoxetine inhibits multiple variants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pathogen causing the coronavirus disease 2019 (COVID-19) worldwide pandemic and multiple observational clinical studies have shown that patients receiving fluoxetine experienced clinical benefit by lowering the risk of intubation and death. The aim of this study is to conduct population pharmacokinetic dosing simulations to quantify the percentage of patients achieving a trough level for the effective concentration resulting in 50% (EC50) and 90% (EC90) inhibition of SARS-CoV-2 as reported in Calu-3 human lung cells. Methods. Pharmacometric parameter estimates used in this study were obtained from the U.S. FDA website from a new drug application for fluoxetine hydrochloride. A population of 1,000 individuals were simulated at standard fluoxetine antidepressant doses (20 mg/day, 30 mg/day, 40 mg/day, 50 mg/day, and 60 mg/day) to estimate the percentage of the patients achieving a trough plasma level for the EC50 and EC90 SARS-CoV-2 inhibition. All analyses and graphing were conducted in R. Results. By day-10 at 20 mg/day 93.2% and 47% of the population will achieve the trough target plasma EC50 and EC90 concentrations, respectively, which translates to a lung tissue distribution coefficient of 60-times higher EC50 (283.6 ng/ml [0.82 mM]) and EC90 (1390.1 ng/ml [4.02 mM]). Further, by day-10 at an ideal dose of 40 mg/day, 99% and 93% of patients will reach the trough EC50 and EC90 concentrations, respectfully. Lastly, only a dose of 60 mg/day will reach the SARS-CoV-2 EC90 inhibitory concentration in the brain. Conclusion. Overall, with a minimum treatment period of 10-days and a minimum dose of 20 mg/day, this study corroborates in vitro studies reporting fluoxetine inhibiting SARS-CoV-2 titers and also multiple observational clinical studies showing therapeutic benefit of fluoxetine in COVID-19 patients.

Advanced spatially hybrid fluid‐kinetic modelling of plasma‐edge neutrals and application to ITER case using SOLPS‐ITER

AbstractA spatially hybrid fluid‐kinetic approach for the efficient simulation of plasma‐edge neutrals is extended with a kinetic‐fluid condensation process and an automated approach to select a fluid or kinetic treatment at each point along the divertor targets. With the proposed hybrid fluid‐kinetic methods, the dominant charge–exchange reaction can be largely removed from the kinetic neutral simulation. The hybrid methods achieve quantitative agreement with the standard kinetic approach, with relative errors on the peak target plasma density and peak target ion flux density of 5–30%, while the Central Processing Unit (CPU) time for the kinetic neutral solver is reduced by a factor 3–6.

Effect of therapeutic drug monitoring-based dose optimization of piperacillin/tazobactam on sepsis-related organ dysfunction in patients with sepsis: a randomized controlled trial

PurposeInsufficient antimicrobial exposure is associated with worse outcomes in sepsis. We evaluated whether therapeutic drug monitoring (TDM)-guided antibiotic therapy improves outcomes.MethodsRandomized, multicenter, controlled trial from January 2017 to December 2019. Adult patients (n = 254) with sepsis or septic shock were randomly assigned 1:1 to receive continuous infusion of piperacillin/tazobactam with dosing guided by daily TDM of piperacillin or continuous infusion with a fixed dose (13.5 g/24 h if eGFR ≥ 20 mL/min). Target plasma concentration was four times the minimal inhibitory concentration (range ± 20%) of the underlying pathogen, respectively, of Pseudomonas aeruginosa in empiric situation. Primary outcome was the mean of daily total Sequential Organ Failure Assessment (SOFA) score up to day 10.ResultsAmong 249 evaluable patients (66.3 ± 13.7 years; female, 30.9%), there was no significant difference in mean SOFA score between patients with TDM (7.9 points; 95% CI 7.1–8.7) and without TDM (8.2 points; 95% CI 7.5–9.0) (p = 0.39). Patients with TDM-guided therapy showed a lower 28-day mortality (21.6% vs. 25.8%, RR 0.8, 95% CI 0.5–1.3, p = 0.44) and a higher rate of clinical (OR 1.9; 95% CI 0.5–6.2, p = 0.30) and microbiological cure (OR 2.4; 95% CI 0.7–7.4, p = 0.12), but these differences did not reach statistical significance. Attainment of target concentration was more common in patients with TDM (37.3% vs. 14.6%, OR 4.5, CI 95%, 2.9–6.9, p < 0.001).ConclusionTDM-guided therapy showed no beneficial effect in patients with sepsis and continuous infusion of piperacillin/tazobactam with regard to the mean SOFA score. Larger studies with strategies to ensure optimization of antimicrobial exposure are needed to definitively answer the question.