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Concurrent cocaine and alcohol use is among the most frequent drug combination, and among the most dangerous in terms of deleterious outcomes. Cocaine increases extracellular monoamines by blocking dopamine (DA), norepinephrine (NE) and serotonin (5-HT) transporters (DAT, NET and SERT, respectively). Likewise, ethanol also increases extracellular monoamines, however evidence suggests that ethanol does so independently of DAT, NET and SERT. Organic cation transporter 3 (OCT3) is an emergent key player in the regulation of monoamine signaling. Using a battery of in vitro, in vivo electrochemical, and behavioral approaches, as well as wild-type and constitutive OCT3 knockout mice, we show that ethanol’s actions to inhibit monoamine uptake are dependent on OCT3. These findings provide a novel mechanistic basis whereby ethanol enhances the neurochemical and behavioral effects of cocaine and encourage further research into OCT3 as a target for therapeutic intervention in the treatment of ethanol and ethanol/cocaine use disorders.

Background and Purpose: A large proportion of ischemic stroke patients lack a definitive stroke etiology despite extensive diagnostic testing. Varicella-Zoster Virus (VZV) can directly invade blood vessels causing vasculitis and may be associated with cryptogenic stroke (CS).Methods: We conducted a retrospective cross-sectional study of CS patients tested for VZV. The following were considered evidence of VZV reactivation (VZV+): positive CSF VZV PCR, anti-VZV IgM in CSF, or anti-VZV IgG CSF/serum ratio of 1:10 or higher. We describe the cohort, report VZV+ proportion with 95% confidence intervals (CI) determined with the Wald method, and compare patient groups using standard statistical tests.Results: A total of 72 CS patients met full study inclusion criteria. Most of the patients were <65 years old, had few traditional vascular risk factors, and had multifocal infarcts. Mean age was 49 years (SD ±13) and 47% were women. A total of 14 patients (19.4%; CI: 11.4-30.8%) had evidence of CNS VZV reactivation. There was no difference in evaluated demographic or radiographic features between those with versus without evidence of VZV reactivation. History of ischemic stroke in the past year (11/14 vs 25/43, P<.05) and hypertension (13/14 vs 35/58 and P<.05) were associated with VZV+.Conclusion: We found a high proportion of CNS VZV reactivation in a cross-sectional cohort of CS patients selected for CSF testing. Testing for VZV might be reasonable in CS patients who are young, have multifocal infarcts, or had an ischemic stroke within the past year, but additional research is needed.

When the velocity shear between the two plasmas separated by Earth's magnetopause is locally super‐Alfvénic, the Kelvin‐Helmholtz (KH) instability can develop. A crucial role is played by the interplanetary magnetic field (IMF) orientation, which can stabilize the velocity shear. Although, in a linear regime, the instability threshold is equally satisfied during both northward and southward IMF orientations, in situ measurements show that KH instability is preferentially excited during the northward IMF orientation. We investigate this different behavior by means of a mixing parameter which we apply to two KH events to identify both boundaries and the center of waves/vortices. During the northward orientation, the waves/vortex boundaries have stronger electrons than ions mixing, while the opposite is observed at their center. During the southward orientation, instead, particle mixing is observed predominantly at the boundaries. In addition, stronger local ion and electron non‐thermal features are observed during the northward than the southward IMF orientation. Specifically, ion distribution functions are more distorted, due to field‐aligned beams, and electrons have a larger temperature anisotropy during the northward than the southward IMF orientation. The observed kinetic features provide an insight into both local and remote processes that affect the evolution of KH structures. Due to the velocity shear layer generated by the solar wind flowing past the Earth's magnetosphere, large surface Kelvin‐Helmholtz (KH) waves and vortices can be formed at the magnetopause. These waves and vortices play a crucial role in transporting the solar wind particles through the magnetopause into the magnetosphere, where the particles form a so‐called low‐latitude boundary layer (LLBL). The particle transport occurs due to stretching and twisting of the magnetic field lines by the KH waves/vortices, which result in plasma mixing and diffusion through the magnetopause. It appears that spacecraft observe the KH waves/vortices more often during northward orientations of the interplanetary magnetic field (IMF). During northward IMF, the induced high‐latitudes reconnection thicken the preexisting LLBL and lower the density gradient at the magnetopause, thus favoring KH instability. Conversely, higher density jump and dayside reconnection, during southward IMF, can suppress the instability development and disrupt the KH vortices. To clarify these differences in the KH wave/vortex appearance under different IMF directions, we compare the wave/vortex and particle properties during both IMF orientations. We employ a mixing parameter, which helps identify specific regions of KH waves/vortices and investigate their kinetic signatures, thus providing an insight into KH evolution. Two Kelvin‐Helmholtz events during northward and southward interplanetary magnetic field (IMF) orientations are compared using a mixing‐parameterHigher mixing and local non‐thermal features due to field‐aligned ion beams during the northward IMF are observedKinetic features of Kelvin‐Helmholtz structures can identify both local and remote processes affecting the instability evolution Two Kelvin‐Helmholtz events during northward and southward interplanetary magnetic field (IMF) orientations are compared using a mixing‐parameter Higher mixing and local non‐thermal features due to field‐aligned ion beams during the northward IMF are observed Kinetic features of Kelvin‐Helmholtz structures can identify both local and remote processes affecting the instability evolution

Crack cocaine smokers who have oral sores may have a greater risk of HIV transmission. Among 2,323 young adults aged 18 years to 29 years from inner-city neighborhoods in New York, Miami and San Francisco, 60% were crack smokers. Oral sores were about two times more likely to be seen in crack smokers than nonsmokers and on those who injected drugs than those who did not. Out of 429 cocaine smokers who reported having receptive oral sex, those with oral sores were more apt to have HIV infection than those who reported no sores.

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Lung transplant recipients are at high risk for herpes zoster and preventive measures are a significant unmet need. We investigated the safety and immunogenicity of two doses of a recombinant zoster vaccine (RZV) in lung transplant recipients (≥50 years). We enrolled 50 patients of which 49 received at least one vaccine dose. Anti‐glycoprotein E (gE) antibody levels (n = 43) increased significantly compared to baseline (median optical density [OD] 1.96; interquartile range [IQR]: 1.17–2.89) after the first (median OD 3.41, IQR 2.54–3.81, p< .0001) and second vaccine dose (median OD 3.63, IQR 3.39–3.86, p< .0001). gE‐specific polyfunctional CD4+ T cell frequencies (n = 38) also increased from baseline (median 85 per 106CD4+ T cells; IQR: 46–180) to the first (median 128 per 106CD4+ T cells; IQR: 82–353; p= .023) and after the second dose (median 361 per 106CD4+ T cells; IQR: 146–848; p< .0001). Tenderness (83.0%; 95%CI: 69.2–92.4%) and redness (31.9%; 95%CI: 19.1–47.1%) at injection site were common. One rejection episode within 3 weeks of vaccination was observed. This is the first study demonstrating that RZV was safe and elicited significant humoral and cell‐mediated immunity in lung transplant recipients. RZV is a new option for the prevention of shingles in this population. The inactivated shingles vaccine is safe and induces both antibody‐ and cell‐mediated responses in lung transplant recipients 50 years of age and older.

Mercury is the smallest and innermost planet of our solar system and has a dipole‐dominated internal magnetic field that is relatively weak, very axisymmetric and significantly offset toward north. Through the interaction with the solar wind, a magnetosphere is created. Compared to the magnetosphere of Earth, Mercury's magnetosphere is smaller and more dynamic. To understand the magnetospheric structures and processes we use in situ MESSENGER data to develop further a semi‐empiric model of the magnetospheric magnetic field, which can explain the observations and help to improve the mission planning for the BepiColombo mission en‐route to Mercury. We present this semi‐empiric KTH22‐model, a modular model to calculate the magnetic field inside the Hermean magnetosphere. Korth et al. (2015, https://doi.org/10.1002/2015JA021022, 2017, https://doi.org/10.1002/2017gl074699) published a model, which is the basis for the KTH22‐model. In this new version, the representation of the neutral sheet current magnetic field is more realistic, because it is now based on observations rather than ad‐hoc assumptions. Furthermore, a new module is added to depict the eastward ring shaped current magnetic field. These enhancements offer the possibility to improve the main field determination. In addition, analyzing the magnetic field residuals allows us to investigate the field‐aligned currents and their possible dependencies on external drivers. We see increasing currents under more disturbed conditions inside the magnetosphere, but no clear dependence on the z‐component of the interplanetary magnetic field nor on the magnetosheath plasma β. We present a revised model of Mercury's magnetospheric magnetic fieldThe model now includes an eastward ring shaped current and the neutral sheet current is calculated more precisely with Biot Savart's lawThe strength of the field‐aligned currents increases with higher magnetic activity We present a revised model of Mercury's magnetospheric magnetic field The model now includes an eastward ring shaped current and the neutral sheet current is calculated more precisely with Biot Savart's law The strength of the field‐aligned currents increases with higher magnetic activity

Magnetotail dipolarization fronts (DFs) are referred as the sharp increase of the northward magnetic field component, embedded in bursts of fast earthward moving plasma flows, so called bursty bulk flows. Earlier studies often considered DFs as tangential discontinuities (TDs), which can be understood as thin vertical current layers of earthward moving flux tubes, so called dipolarzing flux bundles (DFBs), which separate the ambient plasma sheet plasma from the low entropy plasma within the DFB. Here we present a statistical study of 23 DFs observed by the Magnetospheric Multiscale mission during 2017 and 2018 when the apogee was at 25 REin the magnetotail. We perform a test of the Walén relation to distinguish whether the observed DFs have rather a TD or rotational discontinuity character and evaluate the plasma flow across the DFs in detail. The results show that on MHD large scales, all 23 DFs can be considered as TD like, but sometimes may have a significant normal plasma flow across it: for 16 events (∼70%), the plasma flows mainly tangential to the DFs, while for seven events (∼30%), the plasma flows mainly across the DFs. Based on the findings present in this study, we further hypothesize that the DF structure becomes more distorted and unstable in a (locally) more dipolarized background magnetic field region, which may additionally facilitate the plasma flow across the front. Walén test shows that dipolarization fronts (DFs) can generally be classified as tangential discontinuity (TD)‐like structuresPlasma flow across DFs are observed, indicating that they can not be characterized as strict TDsPlasma flow across DFs is larger when background northward magnetic field is stronger

During the first flyby of the BepiColombo composite spacecraft at Mercury in October 2021 ion spectrometers observed two intense spectral lines with energies between 10 and 70 eV. The spectral lines persisted also at larger distances from Mercury and were observed again at lower intensity during cruise phase in March 2022 and at the second and third Mercury flyby as a single band. The ion composition indicates that water is the dominant gas source. The outgassing causes the composite spacecraft to charge up to a negative potential of up to −50 V. The distribution and intensity of the lower energy signal depends on the intensity of low energy electron fluxes around the spacecraft which again depend on the magnetic field orientation. We interpret the observation as being caused by water outgassing from different source locations on the spacecraft being ionized in two different regions of the surrounding potential. The interpretation is confirmed by two dimensional particle‐in‐cell simulations. The BepiColombo spacecraft is on its way through the inner solar system in a composite configuration consisting of two satellites and a propulsion unit with two large solar arrays. This configuration will only be separated after orbit insertion in December 2025. During the cruise phase and planetary flybys in the years 2021–2023 the ion spectrometers onboard the two satellites observed strong fluxes of low energy positive ions. We interpret these observations as being caused by outgassing of water from the spacecraft and a negative charging of the spacecraft caused by a high electron density surrounding the spacecraft. Around the first Mercury flyby in October 2021 all ion spectrometers observed two separate peaks in the low energy ion spectra. We explain these as being caused by water molecules being ionized by strong photon and electron fluxes in different regions of the negative potential surrounding the spacecraft. From these different potential regions ions are accelerated back to the spacecraft. Strong outgassing from the BepiColombo spacecraft was observed during first Mercury Flyby in 2021 and later during interplanetary cruiseThe gas composition is dominated by water moleculesThe ion energy spectra sometimes show a double band structure which we interpret as being caused by different ionization locations within a negative spacecraft potential Strong outgassing from the BepiColombo spacecraft was observed during first Mercury Flyby in 2021 and later during interplanetary cruise The gas composition is dominated by water molecules The ion energy spectra sometimes show a double band structure which we interpret as being caused by different ionization locations within a negative spacecraft potential

We examine a Dipolarization Front (DF) event with an embedded electron diffusion region (EDR), observed by the Magnetospheric Multiscale (MMS) spacecraft on 08 September 2018 at 14:51:30 UT in the Earth's magnetotail by applying multi‐scale multipoint analysis methods. In order to study the large‐scale context of this DF, we use conjunction observations of the Cluster spacecraft together with MMS. A polynomial magnetic field reconstruction technique is applied to MMS data to characterize the embedded electron current sheet including its velocity and the X‐line exhaust opening angle. Our results show that the MMS and Cluster spacecraft were located in two counter‐rotating vortex flows, and such flows may distort a flux tube in a way that the local magnetic shear angle is increased and localized magnetic reconnection may be triggered. Using multi‐point data from MMS we further show that the local normalized reconnection rate is in the range of R∼ 0.16 to 0.18. We find a highly asymmetric electron in‐ and outflow structure, consistent with previous simulations on strong guide‐field reconnection events. This study shows that magnetic reconnection may not only take place at large‐scale stable magnetopause or magnetotail current sheets but also in transient localized current sheets, produced as a consequence of the interaction between the fast Earthward flows and the Earth's dipole field. Magnetic Reconnection is a key energy conversion process, where magnetic energy is converted into kinetic energy of plasma particles. During this process the magnetic field topology changes and the plasma particles decouple from the magnetic field in the so‐called diffusion region and get accelerated, forming a fast outflow jet. Over the last decades, hints arise that reconnection can take place at many different places in the magnetosphere and also very locally and intermittently. Fast plasma flows in the Magnetotail, moving toward the Earth, are assumed to be a consequence of magnetic reconnection, and are often accompanied by dipolar‐shaped magnetic flux bundles, embedded into them. The leading edges of such flux bundles are called dipolarization fronts (DF). In this work, we investigate a DF event, which hosts a diffusion region. First, we study the large‐scale characteristics of the DF, by utilizing data from both the Magnetospheric Multiscale (MMS) and the Cluster mission, that observe different regions of the event almost simultaneously. Second, we performed a 3D magnetic field reconstruction technique and compared the results to MMS data, to investigate the event on small scales. A thin current sheet inside a dipolarization front, embedded in a diverging flow is analyzed using a polynomial reconstruction techniqueTransient reconnection event is detected in a high magnetic shear region, where the magnetic field is deflected due to duskward fast plasma flowThe reconstructed current sheet has a guide field of ∼1.8 the reconnecting component with normalized reconnection rate between 0.16 and 0.18 A thin current sheet inside a dipolarization front, embedded in a diverging flow is analyzed using a polynomial reconstruction technique Transient reconnection event is detected in a high magnetic shear region, where the magnetic field is deflected due to duskward fast plasma flow The reconstructed current sheet has a guide field of ∼1.8 the reconnecting component with normalized reconnection rate between 0.16 and 0.18

Electromagnetic ion cyclotron (EMIC) waves are important for the loss of high‐energy electrons in the radiation belt. Based on the measurements of Van Allen Probes, two events during the same storm period are presented to study the propagation of EMIC waves. In the first event, left‐handed polarized EMIC waves were observed near the plasmapause, while right‐handed waves were observed in the inner plasmasphere. The Poynting flux of the right‐hand waves was mainly directed inward and equatorward, and no positive growth rates were obtained in the region of these right‐hand waves, indicating the inward propagation of the waves from a higher L‐shell. In the second event, the wave vectors were quasi‐perpendicular to the background magnetic field inside the plasmaspheric plume but became quasi‐parallel outside. This phenomenon can be explained by the refraction of the large density gradient, which qualitatively satisfies Snell's law. These observations provide indirect evidence of the inward propagation of the EMIC waves and give a new insight on how density gradients may modify wave properties. Right‐hand EMIC waves are observed in the plasmasphere with inward orientation of Poynting fluxNo positive growth rates are obtained in the region of the right‐hand waves, suggesting a source region in a higher L‐shellAbrupt changes of the wave vector are observed near the inner edge of the plasmaspheric plume

We report on a flapping motion event near the substorm onset on 17 June 2017 using Magnetospheric Multiscale (MMS) mission data. A strong current density with a maximum value of ~190 nA/m2is observed during the flapping. The north‐to‐south (south‐to‐north) crossing of the neutral sheet corresponds to an increase (a decrease) of the ZGSMcomponent of the solar wind VZ, SW. The periods (~8 min) of the flapping and variations of VZ, SWare almost equal. In addition, dVZ, SW/dtand dBX/dtobserved by MMS exhibit a strong negative correlation. These observations suggest that the flapping motions are triggered by the solar wind directional change via creating a motion of the current sheet in the north‐south direction. The pressure difference between the northern and southern lobes caused by the solar wind is expected to be a possible contribution to the formation of the flapping. Flapping motions are large‐amplitude waves of the magnetotail current sheet in the north‐south direction. These waves are believed to be excited in the magnetotail center and then propagate to its flanks. However, their generation mechanisms are not fully understood so far. In this study, we investigate the relation between a flapping motion event and the solar wind parameters. We find that there is a one‐to‐one correspondence between temporal variations of the flapping and the ZGSMcomponent of the solar wind velocity VZ, SW. Moreover, the vertical movement of the ion flow is also in accordance with VZ, SW. These observations suggest that the flapping can be generated by the solar wind directional change. During the flapping, a strong current density with a maximum value of ~190 nA/m2is generated, much larger than the current reported by previous studies. The flapping motion of the current sheet is triggered by the solar wind directional changeVariations of the Zcomponent of the solar wind velocity and BXshow a strong negative correlationAn extremely strong current density with a maximum value of ~190 nA/m2is observed during the flapping

Magnetic reconnection in the magnetotail accelerates plasma in short‐duration bursts of fast flows, referred to as bursty bulk flows toward the Earth. These bursty bulk flows are typically accompanied by a sharp increase in the northward magnetic field component, the so‐called dipolarization front (DF). This rapid increase in northward magnetic field is often preceded by a decrease, the so called DF‐dip, where the northward magnetic field component sometimes even changes sign and turns southward. Here we present a statistical study of the DF‐dip of 43 events, using observations from the Magnetospheric Multiscale (MMS) mission during summer 2017, when MMS's apogee was located in the magnetotail around 25 RE. The 43 events are subdivided into two categories according to their DF‐dip: 20 events where the DF‐dip stays northward (positive DF‐dip category) and 23 events where the DF‐dip turns fully southward (negative DF‐dip category). We find that (1) the magnetic field depression ahead of the DF of the positive DF‐dip events correlates mainly with perpendicular currents and diamagnetic currents flowing ahead of the DF and (2) the magnetic field depression ahead of the DF of the negative DF‐dip events correlates mainly with field‐aligned currents and that this type of events might be (a) earthward moving flux rope‐like structures caused by multiple X‐line reconnection and/or (b) are a result of localized, single X‐line reconnection under a guide field. When magnetic field lines in the Earth's magnetotail reconnect, they shoot earthward like a stretched elastic band. The plasma, connected to the magnetic field, is thereby accelerated. This usually happens repeatedly on short timescales and is called a bursty bulk flow. The reconnected field lines have a more vertical direction, instead of the original horizontal orientation. When the bursty bulk flow crosses over the spacecraft, we see a rapid increase in the vertical (northward) magnetic field component, referred to as dipolarization front, which is usually preceded by a small decrease, the so‐called dipolarization front‐dip. This decrease comes in two categories, one where vertical magnetic field component remains positive (northward) and one where the vertical magnetic field component changes its sign and becomes negative (southward). It is shown that these are two separate categories with different origins. Size of the magnetic field depression ahead of DF correlates with field‐aligned currents if the depression is negative (negative DF‐dip)Size of the magnetic field depression ahead of DF correlates with perpendicular currents if the depression stays positive (positive DF‐dip)Positive DF‐dip events are found closer to flow braking region than negative DF‐dip events

We present Magnetospheric Multiscale observations of an electron‐scale reconnecting current sheet in the mixing region along the trailing edge of a Kelvin‐Helmholtz vortex during southward interplanetary magnetic field conditions. Within this region, we observe intense electrostatic wave activity, consistent with lower‐hybrid waves. These waves lead to the transport of high‐density magnetosheath plasma across the boundary layer into the magnetosphere and generate a mixing region with highly compressed magnetic field lines, leading to the formation of a thin current sheet associated with electron‐scale reconnection signatures. Consistencies between these reconnection signatures and a realistic, local, fully‐kinetic simulation modeling this current sheet indicate a temporal evolution of the observed electron‐scale reconnection current sheet. The multi‐scale and inter‐process character of this event can help us understand plasma mixing connected to the Kelvin‐Helmholtz instability and the temporal evolution of electron‐scale reconnection. Like wind blowing over water, the stream of ionized gas released from the Sun, called the solar wind, can lead to waves and rolled‐up vortex structures at the boundary of Earth's magnetosphere, called the magnetopause. These so‐called Kelvin‐Helmholtz waves have been shown to be connected to various different plasma processes on different scales. This multi‐scale and multi‐process character makes them an ideal candidate to study the relation between these processes from both spacecraft observations and simulations. By using spacecraft data from the Magnetospheric Multiscale mission, which was designed for the study of small‐scale plasma processes in Earth's magnetosphere, we show observations of electron‐scale magnetic reconnection, an explosive energy conversion process in plasmas, in a region along the trailing edge of these waves. These observations shed new light on the multi‐scale and multi‐process character of the Kelvin‐Helmholtz instability and the energy conversion processes along its boundary. A reconnecting electron‐scale current sheet is observed by Magnetospheric Multiscale (MMS) in mixing plasma along the trailing edge of a Kelvin‐Helmholtz vortexRealistic 2.5D fully‐kinetic simulation shows reasonable agreement with MMS dataConsistencies between the simulation and MMS indicate a temporal evolution of the reconnecting current sheet A reconnecting electron‐scale current sheet is observed by Magnetospheric Multiscale (MMS) in mixing plasma along the trailing edge of a Kelvin‐Helmholtz vortex Realistic 2.5D fully‐kinetic simulation shows reasonable agreement with MMS data Consistencies between the simulation and MMS indicate a temporal evolution of the reconnecting current sheet

Human herpes virus 8 (HHV‐8), also known as Kaposi's sarcoma associated herpesvirus (KSHV), is an oncogenic virus that can cause Kaposi's sarcoma (KS). KScan develop following organ transplantation through reactivation of the recipient's latent HHV‐8 infection, or less commonly through donor‐derived infection which has higher risk for severe illness and mortality. We describe a case of probable donor‐derived KSin the recipient of a liver–kidney transplant. The donor had multiple risk factors for HHV‐8 infection. The KSwas successfully treated by switching immunosuppression from tacrolimus to sirolimus. With an increasing number of human immunodeficiency virus (HIV)‐positive persons seeking organ transplantation and serving as organ donors for HIV‐positive recipients, HHV‐8 prevalence among donors and recipients will likely increase and with that the risk for post‐transplant KS. Predetermination of HHV‐8 status can be useful when considering organ donors and recipients with risk factors, although there are currently no validated commercial tests for HHV‐8 antibody screening. With increasing numbers of human immunodeficiency virus–positive individuals receiving organ transplants, and in some cases serving as organ donors, greater awareness of the risk factors for posttransplant Kaposi's sarcoma and measures to reduce its occurrence may be warranted.

Using specific equipment for high temperature fast in-situ X-ray diffraction (iXRD) enables the collection of diffraction patterns over a range of 48 degrees in 2? within one second. In combination with a high-temperature furnace, modifications in the crystallographic structure under a thermal treatment like phase transformations in steel can be observed nearly in real-time. We demonstrate the usefulness of fast high temperature iXRD using the ball bearing steel (100Cr6), which is of high industrial importance for many applications. The specimens were austenitized at 860 °C. Various isothermal annealings were carried out to develop a bainitic steel structure. The transformation was interrupted by further cooling at different stages. The specimens were further investigated with SEM and light microscopy using different etching techniques to correlate the microstructure with the diffraction patterns. We will show that iXRD can help to optimize heat treatments, validate time transformation diagrams and increase the understanding of phase transformations in steels.

Post-licensure surveillance for adverse events following immunizations (AEFI) can identify rare complications of vaccinations and rigorous vaccine adverse event causality assessments can help to identify possible causal relationships. We report the development of arm paralysis after varicella vaccination in a 1-year-old child. Paralysis was initially presumed to be due to vOka because of the temporal relationship between vaccination and onset of arm weakness; however, molecular studies identified wild-type varicella zoster virus VZV (WT-VZV) in the CSF, leading the authors to conclude that WT-VZV was the probable cause. This case illustrates the complexity of assessing AEFI causality, and the importance of careful and complete evaluations when determining the most likely cause of an AEFI.

ABSTRACTInfections of the central nervous system (CNS) are often acute, with significant morbidity and mortality. Routine diagnosis of such infections is limited in developing countries and requires modern equipment in advanced laboratories that may be unavailable to a number of patients in sub-Saharan Africa. We developed a TaqMan array card (TAC) that detects multiple pathogens simultaneously from cerebrospinal fluid. The 21-pathogen CNS multiple-pathogen TAC (CNS-TAC) assay includes two parasites (Balamuthia mandrillarisand Acanthamoeba), six bacterial pathogens (Streptococcus pneumoniae, Haemophilus influenzae, Neisseria meningitidis, Mycoplasma pneumoniae, Mycobacterium tuberculosis, and Bartonella), and 13 viruses (parechovirus, dengue virus, Nipah virus, varicella-zoster virus, mumps virus, measles virus, lyssavirus, herpes simplex viruses 1 and 2, Epstein-Barr virus, enterovirus, cytomegalovirus, and chikungunya virus). The card also includes human RNase P as a nucleic acid extraction control and an internal manufacturer control, GAPDH (glyceraldehyde-3-phosphate dehydrogenase). This CNS-TAC assay can test up to eight samples for all 21 agents within 2.5 h following nucleic acid extraction. The assay was validated for linearity, limit of detection, sensitivity, and specificity by using either live viruses (dengue, mumps, and measles viruses) or nucleic acid material (Nipah and chikungunya viruses). Of 120 samples tested by individual real-time PCR, 35 were positive for eight different targets, whereas the CNS-TAC assay detected 37 positive samples across nine different targets. The CNS-TAC assays showed 85.6% sensitivity and 96.7% specificity. Therefore, the CNS-TAC assay may be useful for outbreak investigation and surveillance of suspected neurological disease.

A kink‐like neutral sheet oscillation event observed by Cluster between 1436 and 1445 UT on 15 October 2004 has been investigated. The oscillations with periods between 40 and 60 s, observed at (−13.1, 8.7, −0.5) RE, are dominant in BXand BY. And they propagate mainly duskward with a velocity of (86, 147, 46) km/s. Their periods and velocity can be explained by the magnetic double‐gradient instability. These oscillations are accompanied by strong field‐aligned currents (FACs), which prefer to occur near the strongly tilted current sheet, and local maximum FAC tends to occur near the neutral sheet. The FACs show one‐to‐one correlated with a high‐latitude Pi2 pulsation event recorded by KTN and TIK stations with a delay time of ~60 and 90 s, respectively. Both the Pi2 and oscillations propagate westward with a comparative conjunctive speed. These findings suggest a strong relation between the FACs and Pi2, and we infer that the Pi2 is caused by the FACs. The periods of the FACs are modulated by the oscillations but not exactly equal, which is one possible reason that the period of the Pi2 caused by the FACs could be different from the oscillations. We speculate that a current circuit between the plasma sheet and ionosphere can be formed during strongly tilted current sheet, and successive tilted current sheet could generate quasiperiodic multiple FAC systems, which can generate high‐latitude Pi2 pulsations and control their periods. Kink‐like neutral sheet oscillations are accompanied by strong field‐aligned currentsThe oscillations could drive high‐latitude Pi2 pulsations via field‐aligned currentsThe magnetic double‐gradient instability can explain these neutral sheet oscillations

We present multipoint observations of earthward moving dipolarization fronts and energetic particle injections from NASA's Magnetospheric Multiscale mission with a focus on electron acceleration. From a case study during a substorm on 02 August 2015, we find that electrons are only accelerated over a finite energy range, from a lower energy threshold at ~7–9 keV up to an upper energy cutoff in the hundreds of keV range. At energies lower than the threshold energy, electron fluxes decrease, potentially due to precipitation by strong parallel electrostatic wavefields or initial sources in the lobes. Electrons at energies higher than the threshold are accelerated cumulatively by a series of impulsive magnetic dipolarization events. This case demonstrates how the upper energy cutoff increases, in this case from ~130 keV to >500 keV, with each dipolarization/injection during sustained activity. We also present a simple model accounting for these energy limits that reveals that electron energization is dominated by betatron acceleration. Electron acceleration in substorm injections can be from a cumulative effect of a series of magnetic dipolarization eventsInjected electron acceleration is most consistent with betatron acceleration over only a finite energy range, from ~10 to a few 100 keVInjections of electrons between ~100 eV and ~10 keV result in a decrease in flux and phase space density as a function of energy

An active storm period in June 2015 showed that particle injection events seen sequentially by the four (Magnetospheric Multiscale) MMS spacecraft subsequently fed the enhancement of the outer radiation belt observed by Van Allen Probes mission sensors. Several episodes of significant southward interplanetary magnetic field along with a period of high solar wind speed (Vsw≳ 500 km/s) on 22 June occurred following strong interplanetary shock wave impacts on the magnetosphere. Key events on 22 June 2015 show that the magnetosphere progressed through a sequence of energy‐loading and stress‐developing states until the entire system suddenly reconfigured at 19:32 UT. Energetic electrons, plasma, and magnetic fields measured by the four MMS spacecraft revealed clear dipolarization front characteristics. It was seen that magnetospheric substorm activity provided a “seed” electron population as observed by MMS particle sensors as multiple injections and related enhancements in electron flux. New MMS data show that magnetic reconnection is a fundamental component of relativistic particle acceleration in Earth's magnetosphereThe composition and timing of substorm injection fronts that supply radiation belt seed particles can be well resolved using MMSCombined RBSP and MMS data demonstrate that magnetospheric substorms are an essential element in the near‐Earth radiation belt system

We present a statistical study of dipolarization fronts (DFs), using magnetic field data from MMS and Cluster, at radial distances below 12 REand 20 RE, respectively. Assuming that the DFs have a semicircular cross section and are propelled by the magnetic tension force, we used multispacecraft observations to determine the DF velocities. About three quarters of the DFs propagate earthward and about one quarter tailward. Generally, MMS is in a more dipolar magnetic field region and observes larger‐amplitude DFs than Cluster. The major findings obtained in this study are as follows: (1) At MMS ∼57 % of the DFs move faster than 150 km/s, while at Cluster only ∼35 %, indicating a variable flux transport rate inside the flow‐braking region. (2) Larger DF velocities correspond to higher Bzvalues directly ahead of the DFs. We interpret this as a snow plow‐like phenomenon, resulting from a higher magnetic flux pileup ahead of DFs with higher velocities. MMS is generally located in a more dipolar magnetic field region and observes larger‐amplitude DFs than Cluster farther down the tailA larger fraction of DFs move faster closer to Earth, suggesting variable flux transport rates in the flow‐braking regionLarger DF velocities correspond to a higher Bz directly ahead of DFs, suggesting a higher flux pileup ahead of DFs with higher velocities

We report on field‐aligned current observations by the four Magnetospheric Multiscale (MMS) spacecraft near the plasma sheet boundary layer (PSBL) during two major substorms on 23 June 2015. Small‐scale field‐aligned currents were found embedded in fluctuating PSBL flux tubes near the separatrix region. We resolve, for the first time, short‐lived earthward (downward) intense field‐aligned current sheets with thicknesses of a few tens of kilometers, which are well below the ion scale, on flux tubes moving equatorward/earthward during outward plasma sheet expansion. They coincide with upward field‐aligned electron beams with energies of a few hundred eV. These electrons are most likely due to acceleration associated with a reconnection jet or high‐energy ion beam‐produced disturbances. The observations highlight coupling of multiscale processes in PSBL as a consequence of magnetotail reconnection. Multipoint multiscale observations of field‐aligned currents during storm time substormsSmall‐scale intense field‐aligned currents are found embedded in PSBL flux tubes near separatrix regionField‐aligned low‐energy electron beams correlate with short‐lived localized field‐aligned currents

Remote observations by the Mariner 10 and MErcury Surface, Space ENvironment, GEophysics, and Ranging (MESSENGER) spacecraft have shown the existence of hydrogen in the exosphere of Mercury. However, to date the hydrogen number densities could only be estimated indirectly from exospheric models, based on the remotely observed Lyman‐α radiances for atomic H, and the detection threshold of the Mariner 10 occultation experiment for molecular H2. Here, we show the first on‐site determined altitude‐density profile of atomic H, derived from in situ magnetic field observations by MESSENGER. The results reveal an extended H exosphere with densities that are ∼1–2 orders of magnitude larger than previously predicted. Using an exospheric model that reproduces the H altitude‐density profile allows us to constrain the so far unknown H2density at the surface, which is ∼2–3 orders of magnitude smaller than previously assumed. These findings demonstrate the importance of (a) in situ measurements supporting remote observations of Mercury's exosphere that will be realized in the near future by the BepiColombo mission and (b) that dissociation processes play a crucial role in Mercury's exosphere. Mercury has an exosphere that contains a variety of species. So far, only two spacecraft have probed the space environment around Mercury: Mariner 10 in 1974–1975 and MErcury Surface, Space ENvironment, GEophysics, and Ranging (MESSENGER) four decades later. Optical observations by Mariner 10 and MESSENGER showed that Mercury has a thin collisionless atmosphere (exosphere) which is abundant in hydrogen. To date the hydrogen number density at Mercury could only be estimated from exospheric models that use the optical observations as constrains, since no in situ measurements of hydrogen are available to determine its exact number density. For the first time, we derive an altitude‐density profile of Mercury's H exosphere from in situ magnetic field measurements by MESSENGER. From the observations of so‐called pick‐up ion cyclotron waves in the magnetic field data, it is possible to derive the local H number density, necessary to excite these waves. The results reveal an extended atomic H exosphere with densities decreasing from ∼100 to 10 cm−3between 2,400 and 15,000 km above the surface. The unexpected large H densities can only be explained by dissociation processes of H2molecules. Here, we introduce an exospheric model that includes such dissociation processes, which allows us for the first time to constrain the H2number density. The results suggests that atomic H has additional sinks near the surface, most likely through chemical reactions with OH and O, and that the photochemistry of H2O in general play an important role for Mercury's exospheric composition. First on‐site determined hydrogen number density in Mercury's exosphereDemonstration that dissociation processes play an important role in Mercury's exosphereBased on the results, we can constrain the so far unknown and overestimated molecular surface number density of hydrogen First on‐site determined hydrogen number density in Mercury's exosphere Demonstration that dissociation processes play an important role in Mercury's exosphere Based on the results, we can constrain the so far unknown and overestimated molecular surface number density of hydrogen

Junction-EBIC is used to characterize minority carrier diffusion lengths in heterojunction thin films. Because the submicron diffusion lengths of our CuInSe2-(Zn,Cd)S film devices and the diameter of the generation volume are in the same range, EBIC interpretation taking the generation volume as a point source is difficult. In our model we use a finite size of the generation volume to fit the EBIC measurements. It is possible to measure with a higher accelerating voltage and for that reason effects caused by surface recombination and high injection can be avoided. In this paper the model is described and experimental results are presented.

We describe a death in a 15-mo-old girl who developed a varicella-like rash 20 d after varicella vaccination that lasted for 2 mo despite acyclovir treatment. The rash was confirmed to be due to vaccine-strain varicella-zoster virus (VZV). This is the first case of fatal varicella due to vaccine-strain VZV reported from the United States. The patient developed severe respiratory complications that worsened with each new crop of varicella lesions; vaccine-strain VZV was detected in the bronchial lavage specimen. Sepsis and multi-organ failure led to death. The patient did not have a previously diagnosed primary immune deficiency, but her failure to thrive and repeated hospitalizations early in life (starting at 5 mo) for presumed infections and respiratory compromise treated with corticosteroids were suggestive of a primary or acquired immune deficiency. Providers should monitor for adverse reactions after varicella vaccination. If severe adverse events develop, acyclovir should be administered as soon as possible. The possibility of acyclovir resistance and use of foscarnet should be considered if lesions do not improve after 10 d of treatment (or if they become atypical [e.g., verrucous]). Experience with use of varicella vaccine indicates that the vaccine has an excellent safety profile and that serious adverse events are very rare and mostly described in immunocompromised patients. The benefit of vaccination in preventing severe disease and mortality outweigh the low risk of severe events occurring after vaccination.

Objectives: To compare the epidemiologic pattern of HIV-1, a recently introduced sexually transmitted disease (STD) agent in Thailand, with the pattern of HSV-2, a well-established STD agent, so that future trends for both viruses can be better understood. Methods: We obtained questionnaire data and determined HSV-2 (by specific gG-2) and HIV-1 seroreactivity in a cohort of 1,115 young male army conscripts who entered service in northern Thailand in 1991. Results: Seroprevalence of HIV-1 and HSV-2 was 6.9% and 14.9 %, respectively. For HSV-2-seropositive men who reported previous genital ulcers, HIV-1 seroprevalence was 32%. For most variables, there was a close correspondence between the prevalence ratios for HIV-1 and for HSV-2, except that prevalence ratios for HIV-1 tended to be greater than the corresponding ratios for HSV-2. The seroprevalence of both viruses was strongly related to early and frequent contact with female sex workers (FSWs), infrequent use of condoms with FSWs, and residence in the upper north region of Thailand. When differences in sexual behavior between the upper north and lower north were controlled for, the seroprevalence of both viruses still differed significantly by region. Conclusions: Although the seroprevalence levels of HSV-2 and HIV-1 were quite different in this cohort of Thai army conscripts in 1991, the patterns of infection in terms of demographic, residential, and behavioral variables were similar. Seroprevalence studies of HSV-2 in other populations, particularly where the HIV-1 epidemic is just beginning, may be useful in predicting which subgroups might be most vulnerable to the epidemic and could therefore benefit the most from public health intervention. Where differences in the patterns of the two viruses have been noted, we hypothesize that the pattern for HIV-1 will evolve toward that seen for HSV-2., Sexual practices substantially influence the risk of herpes simplex virus infection and HIV infection among young men in Thailand. Researchers tested 1,115 young army recruits, and found that 7% were infected with HIV and 15% were infected with herpes. One-third of young men with herpes were also infected with HIV. Infection with these sexually transmitted diseases was closely associated with early and frequent sexual contact with prostitutes, failure to use condoms during sex with prostitutes, and residence in the northern region of Thailand.

Background: A varicella diagnosis or verification of disease history by any healthcare provider is currently accepted for determining evidence of immunity by the Advisory Committee on Immunization Practices (ACIP).Objective: To examine the accuracy of medical record (MR) documented varicella history as a measure of varicella-zoster virus (VZV) immunity among unvaccinated individuals born after 1980. We also assessed methods to practically implement ACIP guidelines to verify varicella history using medical records.Study Design: As part of a larger cross-sectional study conducted at three Philadelphia clinics from 2004–2006, we recruited 536 unvaccinated patients aged 5–19 y (birth years: 1985–2001). Varicella history was obtained from three sources: parent/patient interview, any MR documentation (sick and well visits) and MR documentation of a sick visit for varicella. All participants were tested for VZV IgG. For each source and three age groups (5–9, 10–14, 15–19 y old), positive predictive value (PPV) was calculated. Specificity of varicella history was compared between different sources using McNemar’s Chi-square.Results: Among participants aged 5–9, 10–14 and 15–19 y the PPV for any MR documentation and sick visit diagnosis were 96% and 100%, 92% and 97%, and 99% and 100%, respectively. The specificity for sick visit documentation was higher than any MR documentation and patient/parent recall among all age groups; however, these differences were only statistically significant when comparing sick visit documentation to parent/patient recall for 10-14 y olds.Conclusion: Sick visit documentation of varicella in the MR is an accurate predictor of varicella seropositivity and useful for confirming disease history among unvaccinated persons (birth years: 1985–2001). This method is a practical way to verify varicella history using the ACIP guidelines.

ABSTRACTThe live attenuated Oka varicella vaccine (vOka), derived from clade 2 wild-type (wt) virus pOka, is used for routine childhood immunization in several countries, including the United States, which has caused dramatic declines in the incidence of varicella. vOka can cause varicella, establish latency, and reactivate to cause herpes zoster (HZ). Three loci in varicella-zoster virus (VZV) open reading frame 62 (ORF62) (106262, 107252, and 108111) are used to distinguish vOka from wt VZV. A fourth position (105705) is also fixed for the vOka allele in nearly all vaccine batches. These 4 positions and two vOka mutations (106710 and 107599) reportedly absent from Varivax were analyzed on Varivax-derived ORF62 TOPO TA clones. The wt allele was detected at positions 105705 and 107252 on 3% and 2% of clones, respectively, but was absent at positions 106262 and 108111. Position 106710 was fixed for the wt allele, whereas the vOka allele was present on 18.4% of clones at position 107599. We also evaluated the 4 vOka markers in an isolate obtained from a case of vaccine-caused HZ. The isolate carried the vOka allele at positions 105705, 106262, and 108111. However, at position 107252, the wt allele was present. Thus, all of the ORF62 vOka markers previously regarded as fixed occur as the wt allele in a small percentage of vOka strains. Characterization of all four vOka markers in ORF62 and of the clade 2 subtype marker in ORF38 is now necessary to confirm vOka adverse events.

ABSTRACTPrimary cytomegalovirus (CMV) infection of the mother during pregnancy presents risk of CMV infection of the fetus with resulting permanent disability. CMV IgM antibody is generated following primary CMV infection but also can appear during nonprimary CMV infection and is thus of limited diagnostic use by itself. In contrast, the presence of low CMV IgG avidity has been shown to be a unique and reliable serologic indicator of primary CMV infection. We measured CMV IgG and IgM antibody levels and IgG avidity in sera from a population sample of 6,067 U.S. women aged 12 to 49 years from NHANES (National Health and Nutrition Examination Survey). The CMV IgG prevalence was 58% overall and increased strongly with age. The CMV IgM prevalence was 3.0% overall and remained relatively flat across age groups. The prevalence of low IgG avidity was 2.0% overall, decreased sharply with age, and was seen mainly among IgM-positive sera. Fourteen to 18% of the CMV IgM-positive sera were low IgG avidity, presumably representing primary CMV infection. High CMV IgM antibody titer was a strong predictor of low IgG avidity. The ability to reliably identify primary CMV infection during pregnancy is important for management of the pregnancy, including possible treatment options for the fetus. Both IgM and IgG avidity measurements provide useful clinical information for evaluating primary CMV infection, although commercial tests for CMV IgG avidity are not yet widely available in the United States.

OBJECTIVE To demonstrate varicella zoster virus (VZV) infection in an asymptomatic extracranial (temporal) artery in a patient with ischemic optic neuropathy produced by VZV vasculopathy in whom the pathological changes were mistakenly identified as giant cell arteritis. DESIGN Case report. SETTING Teaching hospital, pathology and virology laboratory. PATIENT An 80-year-old man with left ophthalmic distribution zoster who developed left ischemic optic neuropathy. INTERVENTION An ipsilateral temporal artery biopsy revealed inflammation that was mistakenly identified as giant cell arteritis. The patient was initially treated with steroids but his condition did not improve. When the diagnosis of VZV vasculopathy was confirmed virologically and the patient was treated with intravenous acyclovir, his vision improved. RESULTS Pathological and virological studies provided proof of VZV vasculopathy in the asymptomatic temporal artery. Varicella zoster virus antigen was abundant in arterial adventitia and scattered throughout the media. With intravenous antiviral therapy, the patient's vision improved. CONCLUSION Although in previously studied patients who died of chronic VZV vasculopathy after 10 to 12 months, VZV antigen was present exclusively in the intima, collective analyses of chronic cases and the asymptomatic VZV-infected temporal artery suggest that virus enters arteries through the adventitia and spreads transmurally to the intima.Arch Neurol. 2011;68(4):517-520--