Contributions to Loss Across the Magnetopause During an Electron Dropout Event.

Dropout events are dramatic decreases in radiation belt electron populations that can occur in as little as 30 minutes. Loss to magnetopause due to a combination of magnetopause shadowing and outward radial transport plays a significant role in these events. We examine the dropout of relativistic electron populations during the October 2012 geomagnetic storm using simulated electron phase space density, evaluating the contribution of different processes to losses across the magnetopause. We compare loss contribution from outward transport calculated using a standard empirical radial diffusion model that assumes a dipolar geomagnetic field to an event-specific radial diffusion model evaluated with a non-dipolar geomagnetic field. We additionally evaluate the contribution of Shabansky type 1 particles, which bounce along magnetic field lines with local equatorial maxima, to the loss calculated during this event. We find that the empirical radial diffusion model with a dipolar background field underestimates the contribution of radial diffusion to this dropout event by up to 10% when compared to the event-specific, non-dipolar radial diffusion model. We additionally find that including Shabansky type 1 particles in the initial electron phase space density, that is, allowing some magnetic field lines distorted from the typical single-minima configuration in drift shell construction, increases the calculated loss by an average of 0.75%. This shows that the treatment of the geomagnetic field significantly impacts the calculation of electron losses to the magnetopause during dropout events, with the non-dipolar treatment of radial diffusion being essential to accurately quantify the loss of outer radiation belt populations.

Fast Diffusion of Ultrarelativistic Electrons in the Outer Radiation Belt: 17 March 2015 Storm Event.

Inward radial diffusion driven by ULF waves has long been known to be capable of accelerating radiation belt electrons to very high energies within the heart of the belts, but more recent work has shown that radial diffusion values can be highly event-specific, and mean values or empirical models may not capture the full significance of radial diffusion to acceleration events. Here we present an event of fast inward radial diffusion, occurring during a period following the geomagnetic storm of 17 March 2015. Ultrarelativistic electrons up to ∼8 MeV are accelerated in the absence of intense higher-frequency plasma waves, indicating an acceleration event in the core of the outer belt driven primarily or entirely by ULF wave-driven diffusion. We examine this fast diffusion rate along with derived radial diffusion coefficients using particle and fields instruments on the Van Allen Probes spacecraft mission.

Highly relativistic radiation belt electron acceleration, transport, and loss: Large solar storm events of March and June 2015.

Two of the largest geomagnetic storms of the last decade were witnessed in 2015. On 17 March 2015, a coronal mass ejection-driven event occurred with a Dst (storm time ring current index) value reaching -223 nT. On 22 June 2015 another strong storm (Dst reaching -204 nT) was recorded. These two storms each produced almost total loss of radiation belt high-energy (E ≳ 1 MeV) electron fluxes. Following the dropouts of radiation belt fluxes there were complex and rather remarkable recoveries of the electrons extending up to nearly 10 MeV in kinetic energy. The energized outer zone electrons showed a rich variety of pitch angle features including strong "butterfly" distributions with deep minima in flux at α = 90°. However, despite strong driving of outer zone earthward radial diffusion in these storms, the previously reported "impenetrable barrier" at L ≈ 2.8 was pushed inward, but not significantly breached, and no E ≳ 2.0 MeV electrons were seen to pass through the radiation belt slot region to reach the inner Van Allen zone. Overall, these intense storms show a wealth of novel features of acceleration, transport, and loss that are demonstrated in the present detailed analysis.

Rapid local acceleration of relativistic radiation-belt electrons by magnetospheric chorus.

Recent analysis of satellite data obtained during the 9 October 2012 geomagnetic storm identified the development of peaks in electron phase space density, which are compelling evidence for local electron acceleration in the heart of the outer radiation belt, but are inconsistent with acceleration by inward radial diffusive transport. However, the precise physical mechanism responsible for the acceleration on 9 October was not identified. Previous modelling has indicated that a magnetospheric electromagnetic emission known as chorus could be a potential candidate for local electron acceleration, but a definitive resolution of the importance of chorus for radiation-belt acceleration was not possible because of limitations in the energy range and resolution of previous electron observations and the lack of a dynamic global wave model. Here we report high-resolution electron observations obtained during the 9 October storm and demonstrate, using a two-dimensional simulation performed with a recently developed time-varying data-driven model, that chorus scattering explains the temporal evolution of both the energy and angular distribution of the observed relativistic electron flux increase. Our detailed modelling demonstrates the remarkable efficiency of wave acceleration in the Earth's outer radiation belt, and the results presented have potential application to Jupiter, Saturn and other magnetized astrophysical objects.

Electron acceleration in the heart of the Van Allen radiation belts.

The Van Allen radiation belts contain ultrarelativistic electrons trapped in Earth's magnetic field. Since their discovery in 1958, a fundamental unanswered question has been how electrons can be accelerated to such high energies. Two classes of processes have been proposed: transport and acceleration of electrons from a source population located outside the radiation belts (radial acceleration) or acceleration of lower-energy electrons to relativistic energies in situ in the heart of the radiation belts (local acceleration). We report measurements from NASA's Van Allen Radiation Belt Storm Probes that clearly distinguish between the two types of acceleration. The observed radial profiles of phase space density are characteristic of local acceleration in the heart of the radiation belts and are inconsistent with a predominantly radial acceleration process.

A long-lived relativistic electron storage ring embedded in Earth's outer Van Allen belt.

Since their discovery more than 50 years ago, Earth's Van Allen radiation belts have been considered to consist of two distinct zones of trapped, highly energetic charged particles. The outer zone is composed predominantly of megaelectron volt (MeV) electrons that wax and wane in intensity on time scales ranging from hours to days, depending primarily on external forcing by the solar wind. The spatially separated inner zone is composed of commingled high-energy electrons and very energetic positive ions (mostly protons), the latter being stable in intensity levels over years to decades. In situ energy-specific and temporally resolved spacecraft observations reveal an isolated third ring, or torus, of high-energy (>2 MeV) electrons that formed on 2 September 2012 and persisted largely unchanged in the geocentric radial range of 3.0 to ~3.5 Earth radii for more than 4 weeks before being disrupted (and virtually annihilated) by a powerful interplanetary shock wave passage.

Changes in dopamine, serotonin and their metabolites in discrete brain areas of rat offspring after in utero exposure to cocaine or related drugs.

The concentrations of dopamine (DA), serotonin (5HT) and their metabolites were quantified in 5 brain areas of rats exposed to saline, cocaine (15 mg/kg b.i.d.), amitriptyline (10 mg/kg), or amfonelic acid (AFA, 1.5 mg/kg) throughout gestation. Male pups from 3 similarly treated dams were fostered to 2 surrogate dams. The process of breeding and rearing was repeated 4 times with new dams to build the groups to 4-12, since only one pup per litter was used for any one measurement. AFA was used to mimic the dopamine (DA) uptake blockade and stimulant properties of cocaine and amitriptyline was used to mimic the other pharmacological effects of cocaine. At postnatal days (PND) 30, 60, and 180, one pup per litter was removed for HPLC analysis of monoamines. A second pup received 0.3 mg/kg haloperidol, catalepsy assessed after 1 hr, and the brain used for analysis. The cataleptic response to haloperidol was unaffected by any prenatal treatment. The striatum from PND 30 cocaine rats had decreased levels of DA without a decrease in DA metabolites. At PND 60 in cocaine exposed rats, DA and DOPAC concentrations were increased, and 5HT levels were decreased in the striatum. The amitriptyline-exposed group exhibited decreased 5HT and 5-HIAA levels in the striatum. The hypothalamus of the cocaine group had lower levels of 5-HIAA, and other brain areas had a trend for lower levels of 5HT and 5-HIAA. At PND 180, DOPAC was increased in the striatum and prefrontal cortex of the cocaine group. Haloperidol-induced altered monoamine metabolism was unaffected by any prenatal treatment at any age. These data suggest that age-related changes in the DA and 5HT neurotransmission systems occur in rats exposed prenatally to cocaine. However, the ability of the dopaminergic system to respond to a challenge by a DA receptor blocker is unaltered by these in utero treatments.

Possible involvement of dopamine in the long-term serotonin depletion by p-chloroamphetamine and beta,beta-difluoro-p-chloroamphetamine in rats.

The role of dopamine in the long-term depletion of serotonin in rat brain by p-chloroamphetamine (PCA) and related compounds was investigated by comparing effects of beta,beta-difluoro-p-chloroamphetamine (beta,beta-difluoro-PCA) and 4-methyl-alpha-ethyl-meta-tyramine (H75/12), reported to cause only short-term serotonin depletion, with those of PCA. A single dose of beta,beta-difluoro-PCA had no long-term effects on serotonin in whole rat brain, even after pretreatment with proadifen which decreased the rate at which beta,beta-difluoro-PCA disappeared from brain. The possibility that proadifen might antagonize serotonin depletion was ruled out; proadifen did not prevent long-term serotonin depletion by PCA. Long-term depletion of brain serotonin was found after repeated injections of beta,beta-difluoro-PCA (five injections 4 hr apart) and was prevented by fluoxetine pretreatment. beta,beta-Difluoro-PCA given after the monoamine oxidase inhibitor pargyline or after carbidopa/L-dopa also caused long-term serotonin depletion, although H75/12 did not. At early times after single doses producing the same initial depletion of serotonin, PCA caused a large increase in dopamine and a large decrease in the metabolite 3,4-dihydroxyphenylacetic acid in whole brain, thereby increasing the ratio dopamine/3,4-dihydroxyphenylacetic, and the other two drugs caused smaller effects. Extracellular dopamine was increased markedly by PCA, less by beta,beta-difluoro-PCA, and not at all by H75/12. These results suggest an association between dopamine release and long-term depletion of serotonin and add to evidence that dopamine release by PCA may be essential to its neurotoxic actions on brain serotonin neurons.

Dextromethorphan antagonizes the acute depletion of brain serotonin by p-chloroamphetamine and H75/12 in rats.

A role for calcium in p-chloroamphetamine-induced neurotoxicity has been inferred previously from protective effects of dextromethorphan. We found that dextromethorphan reduces rat brain concentrations of 5-hydroxyindoleacetic acid and blocks the acute, non-neurotoxic depletion of brain serotonin by p-chloroamphetamine and by H75/12. Inhibition of the membrane transporter on brain serotonin neurons by dextromethorphan in vivo might explain its protective effect against p-chloroamphetamine neurotoxicity.

Comparative brain levels of phenylpropanolamine and amphetamine in rats.

The CNS penetration by phenylpropanolamine (PPA) [(+/-)-norephedrine] was examined and compared to that of (+/-)-amphetamine in the rat. Brain and blood levels of the drugs were measured 1 hr after injection of 0.025, 0.05 or 0.1 mmol/kg doses. Brain levels of both drugs were proportional to dose and were several-fold higher than blood levels. Phenylpropanolamine levels in brain and brain:blood concentration ratios were only slightly lower than those of amphetamine at equimolar doses. The results suggest that phenylpropanolamine penetrates the blood:brain barrier almost as well as amphetamine and that different central actions of the two drugs are probably related to pharmacodynamic differences since they could not be accounted for by the small differences in drug concentrations in brain.

MK801 antagonism of the prolonged depletion of striatal dopamine by amphetamine in iprindole-treated rats.

The administration of amphetamine to rats pretreated with iprindole to inhibit the metabolism of amphetamine results in a long-lasting depletion of striatal dopamine and its metabolites, DOPAC and HVA. Pretreatment with MK801, a noncompetitive antagonist of the NMDA (N-methyl-D-aspartate) subclass of excitatory amino acid receptors, antagonized the depletion of striatal dopamine, DOPAC and HVA 3 days after a single dose of amphetamine in iprindole-treated rats. MK801 pretreatment was effective up to 4 hours but not at 8 or 24 hours in preventing amphetamine effects on striatal dopamine, DOPAC and HVA.

Purpose of admission and resource use during cancer hospitalizations.

This study examined the role of purpose of admission (POA) in hospitalizations for lung, colon, and breast cancers, using the 1985 20-percent Medicare provider analysis and review file. Six POA categories were created from discharge abstract data. Average hospitalization charges, per diem charges, length of stay, and rates of death varied significantly by POA (p < .001). Rural and small hospitals were more likely to admit patients for palliation, while urban and large hospitals admitted relatively more patients for active interventions (p < .0001). POA and indicators of case complexity added only modestly to the ability of diagnosis-related groups to predict hospitalization charges.

Long-term consequences of prenatal exposure to cocaine or related drugs: effects on rat brain monoaminergic receptors.

Reports from both this laboratory and others indicate that prenatal exposure of rats to cocaine can produce alterations in development, activity and responses to environmental stimuli. In order to determine a biochemical basis for these effects, radioligand receptor-binding assays for different monoaminergic receptors were performed on rat brain tissues obtained from offspring of dams treated SC with saline, cocaine (15 mg/kg b.i.d.), amitriptyline (10 mg/kg) or amfonelic acid (AFA, 1.5 mg/kg). Male rat pups were fostered by surrogate dams and one rat per litter taken at 30, 60 or 180 days postnatal for determination of striatal and prefrontal cortical D2 receptors, prefrontal cortical 5HT2 receptors, cortical alpha 1-, alpha 2-, beta 1- and beta 2-adrenoceptors. Across all drug treatments and times, the only significant change was at 30 days of age when beta 1-adrenoceptors were increased 68% in the cocaine exposed pups--a time when these rats show hyperactivity--and at 180 days postnatal when a 20% decrease in DA2 receptor Bmax was observed. Also, cortical membrane Mg(2+)-dependent Na+, K(+)-ATPase activities and basal ATPase activities were unaltered by any of the treatments at any of the times. These results suggest that few changes have occurred in monoaminergic receptor sensitivity as a result of the exposure to these drugs during gestation. The behavioral changes that are known to occur following prenatal exposure to cocaine may be due to presynaptic alterations in neurotransmitter function rather than changes in postsynaptic receptors.

Effects of prenatal exposure to cocaine or related drugs on rat developmental and neurological indices.

Although increasing numbers of infants born to cocaine abusing mothers are of grave concern, little is known of the long term development of these children. To determine the long term effects of cocaine on a developing fetus, gravid rats were dosed SC throughout pregnancy with either saline, amfonelic acid (AFA, 1.5 mg/kg), amitriptyline (10 mg/kg) or cocaine (15 mg/kg b.i.d.) and the male pups fostered by surrogate rats. Compared to saline offspring, cocaine- and amitriptyline-exposed litters were underweight at birth, but there were no differences between groups at 15 or 30 days of age. There were more birth defects and stillbirths in cocaine-exposed offspring, however, there were no differences in male/female sex ratios or litter size in any group. Number of days to righting reflex was delayed in the cocaine-exposed group, but there were no changes in time to eye opening. Cocaine- and amitriptyline-exposed pups were hyperactive at 30 days of age, though no differences were found in an initial 15-min exploration period. Only the AFA-exposed offspring were hyperactive at 60 days postnatal. Since cocaine and amitriptyline decreased birth weights, this effect may be related to the nondopaminergic effects of cocaine. These data demonstrate that cocaine exposure in utero at relevant doses can affect neonatal outcome and long term development in rat offspring.

Private sector initiatives in case management.

Case management for high-cost patients is offered by virtually all private insurers and many health management firms. Despite the proliferation of the service, little is known about the process of case management, how it varies among vendors, what its impact is on short- and long-run patient costs, and what its effects are on quality. In this article, the authors present the results of a survey of insurance-based programs that reveal some process variations that could lead to differences in program effectiveness and cost.

Measuring quality in medical case management programs.

Private insurers and health care providers alike currently offer medical case management programs as a means of containing costs and enhancing the quality of care for patients with high-cost illnesses or injuries. Since 1986, Brandeis University's Bigel Institute for Health Policy has been involved in a project to evaluate medical case management programs. The study found that such programs have become popular because of the perception that high-cost patients are typically handled inefficiently. The study also found that greater attention needs to be given to developing systematic ways to measure and monitor the quality of the case management process and its effect on outcomes.