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.

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.

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.

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.

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.

Why does Steady-State Magnetic Reconnection have a Maximum Local Rate of Order 0.1?

Simulations suggest collisionless steady-state magnetic reconnection of Harris-type current sheets proceeds with a rate of order 0.1, independent of dissipation mechanism. We argue this long-standing puzzle is a result of constraints at the magnetohydrodynamic (MHD) scale. We predict the reconnection rate as a function of the opening angle made by the upstream magnetic fields, finding a maximum reconnection rate close to 0.2. The predictions compare favorably to particle-in-cell simulations of relativistic electron-positron and nonrelativistic electron-proton reconnection. The fact that simulated reconnection rates are close to the predicted maximum suggests reconnection proceeds near the most efficient state allowed at the MHD scale. The rate near the maximum is relatively insensitive to the opening angle, potentially explaining why reconnection has a similar fast rate in differing models.

Magnetospheric Multiscale Observations of the Electron Diffusion Region of Large Guide Field Magnetic Reconnection.

We report observations from the Magnetospheric Multiscale (MMS) satellites of a large guide field magnetic reconnection event. The observations suggest that two of the four MMS spacecraft sampled the electron diffusion region, whereas the other two spacecraft detected the exhaust jet from the event. The guide magnetic field amplitude is approximately 4 times that of the reconnecting field. The event is accompanied by a significant parallel electric field (E_{∥}) that is larger than predicted by simulations. The high-speed (∼300 km/s) crossing of the electron diffusion region limited the data set to one complete electron distribution inside of the electron diffusion region, which shows significant parallel heating. The data suggest that E_{∥} is balanced by a combination of electron inertia and a parallel gradient of the gyrotropic electron pressure.

Magnetospheric Multiscale Satellites Observations of Parallel Electric Fields Associated with Magnetic Reconnection.

We report observations from the Magnetospheric Multiscale satellites of parallel electric fields (E_{∥}) associated with magnetic reconnection in the subsolar region of the Earth's magnetopause. E_{∥} events near the electron diffusion region have amplitudes on the order of 100 mV/m, which are significantly larger than those predicted for an antiparallel reconnection electric field. This Letter addresses specific types of E_{∥} events, which appear as large-amplitude, near unipolar spikes that are associated with tangled, reconnected magnetic fields. These E_{∥} events are primarily in or near a current layer near the separatrix and are interpreted to be double layers that may be responsible for secondary reconnection in tangled magnetic fields or flux ropes. These results are telling of the three-dimensional nature of magnetopause reconnection and indicate that magnetopause reconnection may be often patchy and/or drive turbulence along the separatrix that results in flux ropes and/or tangled magnetic fields.

[The regional network ADAPTHERA : Rheumatology care through coordinated cooperation: comprehensive, trans-sectoral, covering all health insurance. Initial results]. / Das landesweite Netzwerk ADAPTHERA : Erste Ergebnisse einer flächendeckenden, krankenkassenübergreifenden und transsektoralen rheumatologischen Versorgung.

The aim of the rheumatology network ADAPTHERA ("risk-adapted rheumatology therapy") is to achieve a comprehensive improvement in rheumatology care by coordinating treatment in a regional, trans-sectoral network. Accompanying biomedical research projects, training concepts, and the construction of a rheumatology register (gathering data and biomaterials) should furthermore ensure the stable and sustainable optimisation of care. In the pilot phase (2012-2015) the focus of the ADAPTHERA network, required as a "regional key project" within the framework of the Initiative on Health Economy of Rheinland-Palatinate (RL-P), Germany, was placed on the optimisation of the early diagnosis of rheumatoid arthritis, where it is well-known that there is a significant care deficit.Through the intensive, stable, and coordinated cooperation of all health care partners in the field of rheumatology (registered general practitioners and orthopaedic specialists, registered core rheumatologists as well as the Association of Rheumatology of RL-P) a unique regional, comprehensive offer with verifiable care optimisation has been established in RL-P. The network is supported by outstanding collaboration with the Association of Statutory Health Insurance Physicians and the self-help organisation Rheumatology League.The aims that were established at the start of the project will be achieved by the end of the pilot phase:- significant improvement in the early diagnosis of rheumatoid arthritis (an average of 23.7 days until diagnosis by rheumatologists)- access covering all health insurance (regardless of the particular scheme the patients belong to)- comprehensive (verifiable participation of general practitioners from all over RL-P)- data and biomaterials collection, established as a basis for biomarker research, and a rheumatology register for RL-P.

The main pillar: Assessment of space weather observational asset performance supporting nowcasting, forecasting, and research to operations.

Space weather forecasting critically depends upon availability of timely and reliable observational data. It is therefore particularly important to understand how existing and newly planned observational assets perform during periods of severe space weather. Extreme space weather creates challenging conditions under which instrumentation and spacecraft may be impeded or in which parameters reach values that are outside the nominal observational range. This paper analyzes existing and upcoming observational capabilities for forecasting, and discusses how the findings may impact space weather research and its transition to operations. A single limitation to the assessment is lack of information provided to us on radiation monitor performance, which caused us not to fully assess (i.e., not assess short term) radiation storm forecasting. The assessment finds that at least two widely spaced coronagraphs including L4 would provide reliability for Earth-bound CMEs. Furthermore, all magnetic field measurements assessed fully meet requirements. However, with current or even with near term new assets in place, in the worst-case scenario there could be a near-complete lack of key near-real-time solar wind plasma data of severe disturbances heading toward and impacting Earth's magnetosphere. Models that attempt to simulate the effects of these disturbances in near real time or with archival data require solar wind plasma observations as input. Moreover, the study finds that near-future observational assets will be less capable of advancing the understanding of extreme geomagnetic disturbances at Earth, which might make the resulting space weather models unsuitable for transition to operations. KEY POINTS: Manuscript assesses current and near-future space weather assetsCurrent assets unreliable for forecasting of severe geomagnetic stormsNear-future assets will not improve the situation.

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.

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.

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.

Ameliorating spatial neglect with non-invasive brain stimulation: from pathophysiological concepts to novel treatment strategies.

Neglect is a multifaceted, complex syndrome, in which patients fail to detect or respond to stimuli or parts thereof located contralesionally. Non-invasive brain stimulation by means of transcranial magnetic stimulation (TMS) or transcranial direct current stimulation (tDCS) may not only be useful as diagnostic research tools to explore the pathophysiology of neglect, but also for ameliorating its symptoms. Current approaches for modulating neglect non-invasively are mainly based on the neurophysiological concept of interhemispheric inhibition, which suggests a pathological overactivation of the contralesional hemisphere due to reduced inhibitory influences from the lesioned one. Within this framework, non-invasive brain stimulation mainly aims to inhibit the contralesional hemisphere to allow for rebalancing the system. However, facilitatory protocols for enhancing the ipsilesional neural circuitry might also prove useful. In this review, we discuss the contribution of non-invasive brain stimulation to current pathological concepts of neglect, the promising results of the proof-of-principle studies currently available as well as the specific aspects to be systematically investigated before broader clinical trials may eventually suggest a routine clinical application.

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.

Bidirectional alterations of interhemispheric parietal balance by non-invasive cortical stimulation.

Transcranial direct current stimulation is a painless, non-invasive brain stimulation technique that allows one to induce polarity-specific excitability changes in the human brain. Here, we investigated, for the first time in a 'proof of principle' study, the behavioural effect of transcranial direct current stimulation on visuospatial attention in both healthy controls and stroke patients suffering from left visuospatial neglect. We applied anodal, cathoP:dal or sham transcranial direct current stimulation (57 microA/cm(2), 10 min) to the left or right posterior parietal cortex. Using a visual detection task in a group of right-handed healthy individuals (n = 20), we observed that transcranial direct current stimulation enhanced or impaired performance depending on stimulation parameters (i.e. current polarity) and stimulated hemisphere. These results are in good accordance with classic models of reciprocal interhemispheric competition ('rivalry'). In a second experiment, we investigated the potential of transcranial direct current stimulation to ameliorate left visuospatial neglect (n = 10). Interestingly, both the inhibitory effect of cathodal transcranial direct current stimulation applied over the unlesioned posterior parietal cortex and the facilitatory effect of anodal transcranial direct current stimulation applied over the lesioned posterior parietal cortex reduced symptoms of visuospatial neglect. Taken together, our findings suggest that transcranial direct current stimulation applied over the posterior parietal cortex can be used to modulate visuospatial processing and that this effect is exerted by influencing interhemispheric reciprocal networks. These novel findings also suggest that a transcranial direct current stimulation-induced modulation of interhemispheric parietal balance may be used clinically to ameliorate visuospatial attention deficits in neglect patients.

The use of tobacco and cannabis at an international music festival.

BACKGROUND: Music festivals are known to attract a high proportion of drug users. METHODS: Using a survey of 1,772 visitors at the Roskilde Festival in Denmark, we assessed substance use at the festival, the incidence of use of substances among never-users and the incidence of use among lifetime users who had not used a substance in the past 12 months. RESULTS: New onset of tobacco use was reported by 9.2% of never-smokers, and new onset of cannabis use was reported by 9.3% of never-smokers of cannabis. Resumption of tobacco use was reported by 24% of past year abstainers, and resumption of cannabis use was reported by 30% of past year abstainers. New onset of other types of substances was reported by less than 0.5% of subjects, but among past year abstainers, 5-10% reported resumption of amphetamine, ketamine, MDMA and cocaine use. New onset smokers of cannabis were significantly younger than never-smokers. CONCLUSION: Music festivals such as the Roskilde Festival may be important arenas for the prevention of onset of tobacco and cannabis use and for a return to substance use.