Full aperture backscatter diagnostics for characterization of laser plasma instabilities at the extreme light infrastructure (ELI) beamlines.

We report on the commissioning of a full aperture backscatter diagnostics station for the kilojoule, nanosecond high repetition rate L4n laser operating at a wavelength of 527 nm at the Extreme Light Infrastructure (ELI) - Beamlines, Dolni Brezany, Czech Republic. Light scattered back from laser-plasma interaction into the cone of the final focusing lens is captured and split into different channels to measure the signatures of laser plasma instabilities from stimulated Brillouin scattering, stimulated Raman scattering, and two plasmon decay with respect to back scattered energy, its spectrum, and its temporal profile. The performance was confirmed in a commissioning experiment with more than 800 shots at laser intensities ranging from 0.5 × 1013 to 1.1 × 1015 W cm-2. These diagnostics are permanently installed at ELI Beamlines, and can be used to understand the details of laser-plasma interactions in experiments with kJ and 527 nm light. The large number of shots that can be collected in an experimental campaign will allow us to study the details of the laser-plasma interaction with a high level of confidence.

Pharmacokinetics and Target Attainment of Antimicrobial Drugs Throughout Pregnancy: Part I-Penicillins.

BACKGROUND AND OBJECTIVE: Pharmacokinetics (PK) are severely altered in pregnant women due to changes in volume of distribution (Vd) and/or drug clearance (CL), affecting target attainment of antibiotics in pregnant women. This review is part of a series that reviews literature on the description of PK and target attainment of antibiotics in pregnant women with specific focus on penicillins. METHODS: A systematic literature search was carried out in PubMed. Articles were labelled as relevant when information on PK of penicillins in pregnant women was available. RESULTS: Thirty-two relevant articles were included, 8 of which discussed amoxicillin (with and without clavulanic acid), 15 ampicillin, 4 benzylpenicillin, 1 phenoxymethylpenicillin, and 4 piperacillin (with and without tazobactam). No studies were found on pheneticillin and flucloxacillin in pregnant women. Ten out of 32 articles included information on both Vd and CL. During the second and third trimester of pregnancy, a higher CL and larger Vd was reported than in non-pregnant women and in pregnant women during first trimester. Reduced target attainment was described in second and third trimester pregnant women. Only 7 studies reported dosing advice, 4 of which were for amoxicillin. CONCLUSION: The larger Vd and higher CL in second and third trimester pregnant women might warrant a higher dosage or shortening of the dosing interval of penicillins to increase target attainment. Studies frequently fail to provide dosing advice for pregnant women, even if the necessary PK information was available.

Magnetic Field Annihilation in a Magnetotail Electron Diffusion Region With Electron-Scale Magnetic Island.

We present observations in Earth's magnetotail by the Magnetospheric Multiscale spacecraft that are consistent with magnetic field annihilation, rather than magnetic topology change, causing fast magnetic-to-electron energy conversion in an electron-scale current sheet. Multi-spacecraft analysis for the magnetic field reconstruction shows that an electron-scale magnetic island was embedded in the observed electron diffusion region (EDR), suggesting an elongated shape of the EDR. Evidence for the annihilation was revealed in the form of the island growing at a rate much lower than expected for the standard X-type geometry of the EDR, which indicates that magnetic flux injected into the EDR was not ejected from the X-point or accumulated in the island, but was dissipated in the EDR. This energy conversion process is in contrast to that in the standard EDR of a reconnecting current sheet where the energy of antiparallel magnetic fields is mostly converted to electron bulk-flow energy. Fully kinetic simulation also demonstrates that an elongated EDR is subject to the formation of electron-scale magnetic islands in which fast but transient annihilation can occur. Consistent with the observations and simulation, theoretical analysis shows that fast magnetic diffusion can occur in an elongated EDR in the presence of nongyrotropic electron effects. We suggest that the annihilation in elongated EDRs may contribute to the dissipation of magnetic energy in a turbulent collisionless plasma.

Parker Solar Probe Observations of Solar Wind Energetic Proton Beams Produced by Magnetic Reconnection in the Near-Sun Heliospheric Current Sheet.

We report observations of reconnection exhausts in the Heliospheric Current Sheet (HCS) during Parker Solar Probe Encounters 08 and 07, at 16 R s and 20 R s , respectively. Heliospheric current sheet (HCS) reconnection accelerated protons to almost twice the solar wind speed and increased the proton core energy by a factor of ∼3, due to the Alfvén speed being comparable to the solar wind flow speed at these near-Sun distances. Furthermore, protons were energized to super-thermal energies. During E08, energized protons were found to have leaked out of the exhaust along separatrix field lines, appearing as field-aligned energetic proton beams in a broad region outside the HCS. Concurrent dropouts of strahl electrons, indicating disconnection from the Sun, provide further evidence for the HCS being the source of the beams. Around the HCS in E07, there were also proton beams but without electron strahl dropouts, indicating that their origin was not the local HCS reconnection exhaust.

Prescription opioids among older adults: ten years of data across five countries.

BACKGROUND: Opioid use has increased globally in the recent decade. Although pain remains a significant problem among older adults, susceptibility to opioid-related harms highlights the importance of careful opioid therapy monitoring on individual and societal levels. We aimed to describe the trends of prescription opioid utilisation among residents aged ≥65 in all Nordic countries during 2009-2018. METHODS: We conducted cross-sectional measurements of opioid utilisation in 2009-2018 from nationwide registers of dispensed drugs in Denmark, Finland, Iceland, Norway, and Sweden. The measures included annual opioid prevalence, defined daily doses (DDDs) per 1000 inhabitants per day (DIDs), and morphine milligram equivalents (MMEs) per user per day. RESULTS: From 2009 to 2018, an average of 808,584 of adults aged ≥65 used opioids yearly in all five countries; an average annual prevalence of 17.0%. During this time period, the prevalence decreased in Denmark, Norway, and Sweden due to declining codeine and/or tramadol use. Iceland had the highest opioid prevalence in 2009 (30.2%), increasing to 31.7% in 2018. In the same period, DIDs decreased in all five countries, and ranged from 28.3 in Finland to 58.5 in Denmark in 2009, and from 23.0 in Finland to 54.6 in Iceland in 2018. MMEs/user/day ranged from 4.4 in Iceland to 19.6 in Denmark in 2009, and from 4.6 in Iceland to 18.8 in Denmark in 2018. In Finland, Norway, and Sweden, MMEs/user/day increased from 2009 to 2018, mainly due to increasing oxycodone utilisation. CONCLUSIONS: The stable or decreasing opioid utilisation prevalence among a majority of older adults across the Nordic countries coincides with an increase in treatment intensity in 2009-2018. We found large cross-national differences despite similarities across the countries' cultures and healthcare systems. For the aged population, national efforts should be placed on improving pain management and monitoring future trends of especially oxycodone utilisation.

Spatially resolved online particle detector using scintillators for laser-driven particle sources.

Laser-based particle accelerators have been an active field of research for over two decades moving from laser systems capable of one shot every hour to systems able to deliver repetition rates in the Hz regime. Based on the advancements in laser technology, the corresponding detection methods need to develop from single to multiple use with high readout speed. Here, we present an online compact tracker of particles using scintillators with nine resolvable energy levels and a spatial resolution of 3.6 × 3.6 mm2 over the whole active area. This paper describes the design and construction of the detector, which is based on pixellated scintillators embedded inside an absorber matrix. The scintillator pixels are fiberoptically coupled to a camera system for online readout and analysis. Calibration with a radioactive source and first experimental data measuring laser accelerated ions at the PHELIX laser at GSI, Darmstadt, Germany, are presented and discussed.

Microstructured layered targets for improved laser-induced x-ray backlighters.

We present the usage of two-layer targets with laser-illuminated front-side microstructures for x-ray backlighter applications. The targets consisted of a silicon front layer and copper back side layer. The structured layer was irradiated by the 500-fs PHELIX laser with an intensity above 10^{20}Wcm^{-2}. The total emission and one-dimensional extent of the copper Kα x-ray emission as well as a wide spectral range between 7.9 and 9.0 keV were recorded with an array of crystal spectrometers. The measurements show that the front-side modifications of the silicon in the form of conical microstructures maintain the same peak brightness of the Kα emission as flat copper foils while suppressing the thermal emission background significantly. The observed Kα source sizes can be influenced by tilting the conical microstructures with respect to the laser axis. Overall, the recorded copper Kα photon yields were in the range of 10^{11}sr^{-1}, demonstrating the suitability of these targets for probing applications without subjecting the probed material to additional heating from thermal line emission.

Lower-Hybrid Drift Waves Driving Electron Nongyrotropic Heating and Vortical Flows in a Magnetic Reconnection Layer.

We report measurements of lower-hybrid drift waves driving electron heating and vortical flows in an electron-scale reconnection layer under a guide field. Electrons accelerated by the electrostatic potential of the waves exhibit perpendicular and nongyrotropic heating. The vortical flows generate magnetic field perturbations comparable to the guide field magnitude. The measurements reveal a new regime of electron-wave interaction and how this interaction modifies the electron dynamics in the reconnection layer.

[ADAPTHERA-Statewide cross-sectoral care network for patients with early rheumatoid arthritis shows sustained remission in standard care]. / ADAPTHERA ­ Landesweit transsektorales Versorgungsnetzwerk für Patienten mit früher rheumatoider Arthritis zeigt anhaltende Remissionen in der Regelversorgung.

BACKGROUND/OBJECTIVE: The majority of patients in Germany miss out on the necessity of early diagnosis and initiation of therapy for rheumatoid arthritis (RA) caused by considerable structural deficits in the health care system. The challenge is to reconcile the individual demand for the best possible therapy result with a sustainable expenditure of resources. METHODS: The cross-sectoral regional care network ADAPTHERA aims to improve early RA diagnosis and treatment in Rhineland-Palatinate. The retrospective triage analyses of suspected early onset RA patients was performed by tracing the selection process of all available enquiries (n = 1045). For analysis of the clinical course of the disease, a subset comprising 143 patients with a minimum observation time of 12 months (5 consecutive visits) was available. Clinical and laboratory parameters were collected quarter yearly, self-administered questionnaires were filled out and the treatment was adapted if necessary. RESULTS: A total of 454 patients were included. The mean waiting time was 23.9 (SD = 18) days. The mean observation period in the subcohort was 29.2 (SD = 12.7) months, with about 50% of the patients presenting within 3 months. Almost 75% of the patients were in remission after 2 years. A sustained remission could be described for 74.8% (6 months) and 53.5% (12 months), respectively. Especially patients with rapid remission induction benefited in terms of longer remissions (p = 0.03). A very early stage of the disease (VERA) was associated with a rarely necessary biologic therapy (p = 0.022). DISCUSSION: The approach of a supply network is not a panacea, but it might improve healthcare for patients with early onset RA. In order to minimize resource utilization, a pinpoint referral and accurate triage of potential cases are crucial.

Development and validation of a semi-automated surveillance system-lowering the fruit for non-ventilator-associated hospital-acquired pneumonia (nvHAP) prevention.

OBJECTIVES: Conducting manual surveillance of non-ventilator-associated hospital-acquired pneumonia (nvHAP) using ECDC (European Centre for Disease Prevention and Control) surveillance criteria is very resource intensive. We developed and validated a semi-automated surveillance system for nvHAP, and describe nvHAP incidence and aetiology at our hospital. METHODS: We applied an automated classification algorithm mirroring ECDC definition criteria to distinguish patients 'not at risk' from patients 'at risk' for suffering from nvHAP. 'At risk'-patients were manually screened for nvHAP. For validation, we applied the reference standard of full manual evaluation to three validation samples comprising 2091 patients. RESULTS: Among the 39 519 University Hospital Zurich inpatient discharges in 2017, the algorithm identified 2454 'at-risk' patients, reducing the number of medical records to be manually screened by 93.8%. From this subset, nvHAP was identified in 251 patients (0.64%, 95%CI: 0.57-0.73). Sensitivity, negative predictive value, and accuracy of semi-automated surveillance versus full manual surveillance were lowest in the validation sample consisting of patients with HAP according to the International Classification of Diseases (ICD-10) discharge diagnostic codes, with 97.5% (CI: 93.7-99.3%), 99.2% (CI: 97.9-99.8%), and 99.4% (CI: 98.4-99.8%), respectively. The overall incidence rate of nvHAP was 0.83/1000 patient days (95%CI: 0.73-0.94), with highest rates in haematology/oncology, cardiac and thoracic surgery, and internal medicine including subspecialties. CONCLUSIONS: The semi-automated surveillance demonstrated a very high sensitivity, negative predictive value, and accuracy. This approach significantly reduces manual surveillance workload, thus making continuous nvHAP surveillance feasible as a pivotal element for successful prevention efforts.

Development of a brain simulator for intracranial targeting: Technical note.

Learning and enhancing of manual skills in the field of neurosurgery requires an intensive training which can be maintained by using virtual reality (VR)-based or physical model (PM)-based simulators. However, both simulator types are limited to one specific intracranial procedure, e.g. the application of an external ventricular drainage (EVD), and they do not provide any accuracy verification. We present a brain simulator which consists of a 3D human skull model having five electroconductive balls in its interior. The installed balls represent intracranial target points providing various accuracy problems in neuronavigation. They are electrically contacted to lamps getting an optical signal by touching them with a current-carrying target tool. The simulator fulfills two requirements: First, it can prove the accuracy of navigation systems and algorithms. Second, it allows becoming familiar with a navigation system's application in an ex vivo setting. It could be a helpful device in neurosurgical skills labs.

The two-fluid dynamics and energetics of the asymmetric magnetic reconnection in laboratory and space plasmas.

Magnetic reconnection is a fundamental process in magnetized plasma where magnetic energy is converted to plasma energy. Despite huge differences in the physical size of the reconnection layer, remarkably similar characteristics are observed in both laboratory and magnetosphere plasmas. Here we present the comparative study of the dynamics and physical mechanisms governing the energy conversion in the laboratory and space plasma in the context of two-fluid physics, aided by numerical simulations. In strongly asymmetric reconnection layers with negligible guide field, the energy deposition to electrons is found to primarily occur in the electron diffusion region where electrons are demagnetized and diffuse. A large potential well is observed within the reconnection plane and ions are accelerated by the electric field toward the exhaust region. The present comparative study identifies the robust two-fluid mechanism operating in systems over six orders of magnitude in spatial scales and over a wide range of collisionality.

90Y TOF-PET based EUD reunifies patient survival prediction in resin and glass microspheres radioembolization of HCC tumours.

Clinical studies reported a twofold ratio between the efficacies per Gy of resin versus glass spheres. Our aim is to investigate whether this difference could result from the different degrees of heterogeneity in sphere distribution between the two medical devices. The 90Y TOF-PET based equivalent uniform doses (EUD) was used for this purpose. 58 consecutive HCC radioembolizations were retrospectively analyzed. Absorbed doses D and Jones-Hoban EUD in lesions were computed. Radioembolization efficacy was assessed using Kaplan-Meier survival curves. In order to match together the glass and resin spheres survival curves using a 40 Gy-threshold, an efficacy factor of 0.73 and 0.36 has to be applied on their absorbed dose, respectively. Using EUD, a nice matching between glass and resin survival curves was obtained with a better separation of the responding and not responding survival curves. The results clearly support the fact that the activity heterogeneity observed in 90Y TOF-PET post radioembolization does not only result from statistical noise, but also reflects the actual heterogeneity of the spheres distribution. Use of EUD reunifies the efficacy of the two medical devices.

Electron-scale dynamics of the diffusion region during symmetric magnetic reconnection in space.

Magnetic reconnection is an energy conversion process that occurs in many astrophysical contexts including Earth's magnetosphere, where the process can be investigated in situ by spacecraft. On 11 July 2017, the four Magnetospheric Multiscale spacecraft encountered a reconnection site in Earth's magnetotail, where reconnection involves symmetric inflow conditions. The electron-scale plasma measurements revealed (i) super-Alfvénic electron jets reaching 15,000 kilometers per second; (ii) electron meandering motion and acceleration by the electric field, producing multiple crescent-shaped structures in the velocity distributions; and (iii) the spatial dimensions of the electron diffusion region with an aspect ratio of 0.1 to 0.2, consistent with fast reconnection. The well-structured multiple layers of electron populations indicate that the dominant electron dynamics are mostly laminar, despite the presence of turbulence near the reconnection site.

Orientation and Stability of Asymmetric Magnetic Reconnection X Line.

The orientation and stability of the reconnection x line in asymmetric geometry is studied using three-dimensional (3-D) particle-in-cell simulations. We initiate reconnection at the center of a large simulation domain to minimize the boundary effect. The resulting x line has sufficient freedom to develop along an optimal orientation, and it remains laminar. Companion 2-D simulations indicate that this x line orientation maximizes the reconnection rate. The divergence of the nongyrotropic pressure tensor breaks the frozen-in condition, consistent with its 2-D counterpart. We then design 3-D simulations with one dimension being short to fix the x line orientation but long enough to allow the growth of the fastest growing oblique tearing modes. This numerical experiment suggests that reconnection tends to radiate secondary oblique tearing modes if it is externally (globally) forced to proceed along an orientation not favored by the local physics. The development of oblique structure easily leads to turbulence inside small periodic systems.

Strongly localized magnetic reconnection by the super-Alfvénic shear flow.

We demonstrate that the dragging of the magnetic field by the super-Alfvénic shear flows out of the reconnection plane can strongly localize the reconnection x-line in collisionless pair plasmas, reversing the current direction at the x-line. Reconnection with this new morphology, which is impossible in resistive-magnetohydrodynamics, is enabled by the particle inertia. Surprisingly, the quasi-steady reconnection rate remains of order 0.1 even though the aspect ratio of the local x-line geometry is larger than unity, which completely excludes the role of tearing physics. We explain this by examining the transport of the reconnected magnetic flux and the opening angle ma de by the upstream magnetic field, concluding that the reconnection rate is still limited by the constraint imposed at the inflow region. Based on these findings, we propose that this often observed fast rate value of order 0.1 itself, in general, is an upper bound value determined by the upstream constraint, independent of the localization mechanism and dissipation therein.

On the Collisionless Asymmetric Magnetic Reconnection Rate.

A prediction of the steady state reconnection electric field in asymmetric reconnection is obtained by maximizing the reconnection rate as a function of the opening angle made by the upstream magnetic field on the weak magnetic field (magnetosheath) side. The prediction is within a factor of 2 of the widely examined asymmetric reconnection model (Cassak & Shay, 2007, https://doi.org/10.1063/1.2795630) in the collisionless limit, and they scale the same over a wide parameter regime. The previous model had the effective aspect ratio of the diffusion region as a free parameter, which simulations and observations suggest is on the order of 0.1, but the present model has no free parameters. In conjunction with the symmetric case (Liu et al., 2017, https://doi.org/10.1103/PhysRevLett.118.085101), this work further suggests that this nearly universal number 0.1, essentially the normalized fast-reconnection rate, is a geometrical factor arising from maximizing the reconnection rate within magnetohydrodynamic-scale constraints. PLAIN LANGUAGE SUMMARY: To understand the evolution of many space and astrophysical plasmas, it is imperative to know how fast magnetic reconnection processes the magnetic flux. Researchers found that reconnection in both symmetric and asymmetric geometries exhibits a normalized reconnection rate of order 0.1. In this work, we show that this nearly universal value in asymmetric geometry is also the maximal rate allowed in the magnetohydrodynamic scale. This result has applications to the transport process at plasma boundary layers like Earth's magnetopause.

Electron Bulk Acceleration and Thermalization at Earth's Quasiperpendicular Bow Shock.

Electron heating at Earth's quasiperpendicular bow shock has been surmised to be due to the combined effects of a quasistatic electric potential and scattering through wave-particle interaction. Here we report the observation of electron distribution functions indicating a new electron heating process occurring at the leading edge of the shock front. Incident solar wind electrons are accelerated parallel to the magnetic field toward downstream, reaching an electron-ion relative drift speed exceeding the electron thermal speed. The bulk acceleration is associated with an electric field pulse embedded in a whistler-mode wave. The high electron-ion relative drift is relaxed primarily through a nonlinear current-driven instability. The relaxed distributions contain a beam traveling toward the shock as a remnant of the accelerated electrons. Similar distribution functions prevail throughout the shock transition layer, suggesting that the observed acceleration and thermalization is essential to the cross-shock electron heating.

Population Mixing in Asymmetric Magnetic Reconnection with a Guide Field.

We investigate how population mixing leads to structured electron distribution functions in asymmetric guide-field magnetic reconnection based on particle-in-cell simulations. The change of magnetic connectivity patches populations from different inflow regions to form multicomponent distributions in the exhaust, illustrating the direct consequence of the breaking and rejoining of magnetic flux tubes. Finite Larmor radius (FLR) effects of electrons accelerated by the perpendicular electric fields result in crescent-type nongyrotropic distributions. A new type of nongyrotropy is found to be caused by the combined effects of the FLR and velocity dispersion of electrons accelerated by the parallel electric field. The patching together of populations and the effects of acceleration and the FLR form the first steps of mixing in the exhaust and separatrix regions.