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Auroral precipitation plays an important role in magnetosphere-ionosphere-thermosphere (MIT) coupling by enhancing ionospheric ionization and conductivity at high latitudes. Diffuse electron precipitation refers to scattered electrons from the plasma sheet that are lost in the ionosphere. Diffuse precipitation makes the largest contribution to the total precipitation energy flux and is expected to have substantial impacts on the ionospheric conductance and affect the electrodynamic coupling between the magnetosphere and ionosphere-thermosphere. Kinetic theory and observational analysis also demonstrate that diffuse precipitation is subject to multiple reflection effects, i.e. secondary electrons produced by the primary precipitation are reflected between the north and south hemispheres multiple times before they are fully lost in the atmosphere. In this study, we make use of the newly developed Multiscale Atmosphere-Geospace Environment (MAGE) model developed at the NASA DRIVE Science Center for Geospace Storms (CGS) to explore the role of diffuse electron precipitation in MIT coupling. Diffuse precipitation in MAGE is derived from the electron distribution in the Rice Convection Model (RCM), a ring current model that solves for energy dependent drifts of electrons and ions. Diffuse precipitation, together with mono-energetic electron precipitation based on parameterization of the magnetohydrodynamic (MHD) parameters from the Grid Agnostic MHD with Extended Research Applications (GAMERA) magnetosphere model, are input to the Thermosphere Ionosphere Electrodynamic General Circulation Model (TIEGCM) to calculate the ionospheric ionization rate and conductivity and height-integrated conductance. With controlled numerical experiments, we investigate 1. how the diffuse precipitation affects the location and structure of a mesoscale ionospheric convection process, i.e., subauroral polarization streams (SAPS); 2. How multiple reflection effects impact the ionosphere-thermosphere and their coupling with the magnetosphere. Our study demonstrates that diffuse electron precipitation plays a critical role in determining the location and structure of SAPS. The multiple reflection effects make diffuse precipitation number flux and energy flux a few times higher than the unmodified precipitation, resulting in a greatly enhanced auroral ionospheric conductance, lower cross polar cap potential, higher total field-aligned currents, and changes in global thermospheric winds and temperature. Therefore, diffuse electron precipitation has both local and global impacts on MIT coupling.

BACKGROUND It has long been well-established that Clostridiodes difficile infections (CDI) can cause severe morbidity and mortality. However, most of the literature to date has focused on hospital-diagnosed infections with less emphasis on clinic-based CDI cases. Guidelines from the 2010 IDSA/SHEA for CDI advocate for metronidazole as first-line therapy for mild to moderate CDI cases. However, the 2017 guidelines recommend oral vancomycin or fidaxomicin as first-line therapy due to their superior efficacy. Objective: The purpose of this study was to compare Clostriodes difficile infections in convenience samples of clinic vs. hospital patients. METHODS In 2019, a retrospective, case-controlled study was performed by the first six authors between 2015-2017 (i.e., prior to the 2017 IDSA/SHEA CDI guidelines) to compare ambulatory and hospital CDI treatment prescriptions. Analytic data included frequency of White blood cells (WBC) and creatinine collection, frequency of severe CDI cases, compliance with the 2010 guidelines, CDI recurrence, and mortality. RESULTS An eligible subgroup of N = 92 hospital patients at Spectrum Health Lakeland were more likely to have WBC (98.4% vs 32.6%, p

We have taken a key step in evaluating the importance of ionospheric outflows relative to electrodynamic coupling in the thermosphere’s impact on geospace dynamics. We isolated the thermosphere’s m...

Motivated by low-altitude cusp observations of small-scale (~ 1 km) field-aligned currents (SSFACs) interpreted as ionospheric Alfv\'en resonator modes, we investigated the effects of Alfv\'en wave energy deposition on thermospheric upwelling and the formation of air density enhancements in and near the cusp. Such density enhancements were commonly observed near 400 km altitude by the CHAMP satellite. They are not predicted by empirical thermosphere models, and they are well-correlated with the observed SSFACs. A parameterized model for the altitude dependence of the Alfv\'en wave electric field, constrained by CHAMP data, has been developed and embedded in the Joule heating module of the National Center for Atmospheric Research (NCAR) Coupled Magnetosphere-Ionosphere-Thermosphere (CMIT) model. The CMIT model was then used to simulate the geospace response to an interplanetary stream interaction region (SIR) that swept past Earth on 26-27 March 2003. CMIT diagnostics for the thermospheric mass density at 400 km altitude show: 1) CMIT without Alfv\'enic Joule heating usually underestimates CHAMP's orbit-average density; inclusion of Alfv\'enic heating modestly improves CMIT's orbit-average prediction of the density (by a few %), especially during the more active periods of the SIR event. 2) The improvement in CMIT's instantaneous density prediction with Alfv\'enic heating included is more significant (up to 15%) in the vicinity of the cusp heating region, a feature that the MSIS empirical thermosphere model misses for this event. Thermospheric density changes of 20-30% caused by the cusp-region Alfv\'enic heating sporadically populate the polar region through the action of corotation and neutral winds., Comment: 15 pages, 6 figures, Supporting Information (10 pages, 5 figures)

When solving hydrodynamic equations in spherical/cylindrical geometry using explicit finite difference schemes, a major difficulty is that the time step is greatly restricted by the clustering of azimuthal cells near the pole due to the Courant-Friedrichs-Lewy condition. This paper adapts the azimuthal averaging-reconstruction (Ring Average) technique to finite difference schemes in order to mitigate the time step constraint in spherical/cylindrical coordinates. The finite-difference Ring Average technique averages physical quantities based on an effective grid and then reconstructs the solution back to the original grid in a piece-wise, monotonic way. The algorithm is implemented in a community upper atmospheric model Thermosphere-Ionosphere Electrodynamics General Circulation Model (TIE-GCM), with horizontal resolution up to 0.625 × 0.625 in the geographic longitude-latitude coordinates, which enables the capability of resolving critical mesoscale structures within the TIE-GCM. Numerical experiments have shown that the Ring Average technique introduces minimal artifacts in the polar region of the GCM solutions, which is a significant improvement compared to the commonly used low-pass filtering techniques such as the fast Fourier transform method. Since the finite-difference adaption of the Ring Average technique is a post-solver type algorithm, which requires no changes to the original computational grid and numerical algorithms, it has also been implemented in much more complicated models with extended physical/chemical modules such as the coupled Magnetosphere Ionosphere Thermosphere (CMIT) model and the Whole Atmosphere Community Climate Model with thermosphere and ionosphere eXtension (WACCM-X). The implementation of the Ring Average techniques in both models enables CMIT and WACCM-X to perform global simulations with a much higher resolution than that used in the community versions. The new technique is not only a significant improvement in space weather modeling capability, but can also be adapted to more general finite difference solvers for hyperbolic equations in spherical/polar geometries.

Magnetic shielding concepts were investigated for the Reaction Wheel Assembly on the NASA Europa Clipper spacecraft. This investigation was performed in order to mitigate the magnetic incompatibility between the Reaction Wheel Assembly (RWA) and the two magnetically sensitive science instruments on the Europa Clipper spacecraft. Given the Reaction Wheel Assembly's mass and space design constraints, two magnetic shielding concepts were taken into consideration: (1) magnetic shielding of the internal magnet of the RWA Wheel Unit using Mu-metal material and (2) magnetic shielding of the entire RWA Wheel Unit using Metglas material.

BACKGROUND It has long been well-established that Clostridiodes difficile infections (CDI) can cause severe morbidity and mortality. However, most of the literature to date has focused on hospital-diagnosed infections with less emphasis on clinic-based CDI cases. Guidelines from the 2010 IDSA/SHEA for CDI advocate for metronidazole as first-line therapy for mild to moderate CDI cases. However, the 2017 guidelines recommend oral vancomycin or fidaxomicin as first-line therapy due to their superior efficacy. Objective: The purpose of this study was to compare Clostriodes difficile infections in convenience samples of clinic vs. hospital patients. METHODS In 2019, a retrospective, case-controlled study was performed by the first six authors between 2015-2017 (i.e., prior to the 2017 IDSA/SHEA CDI guidelines) to compare ambulatory and hospital CDI treatment prescriptions. Analytic data included frequency of White blood cells (WBC) and creatinine collection, frequency of severe CDI cases, compliance with the 2010 guidelines, CDI recurrence, and mortality. RESULTS An eligible subgroup of N = 92 hospital patients at Spectrum Health Lakeland were more likely to have WBC (98.4% vs 32.6%, p CONCLUSIONS Based on these results, assessment of CDI severity remains limited in the ambulatory population due to the lack of severity markers. It is unclear if this is due to lack of available laboratory resources or difference in clinical presentation. Of those sample patients who have available markers of severity, patients receiving clinic-based diagnoses were less likely assessed to have severe CDI. Keywords: Cloistriodes difficile infection, ambulatory, severity markers

Secretory phospholipase A2 group IIA (PLA2G2A) is a phospholipase which has a role in inflammation, atherogenesis, and host defense. Previously, we found that PLA2G2A protects mice on high-fat diets from weight gain and insulin resistance. Here, we examined the regulation of PLA2G2A and the metabolic changes that occur in response to variations in thyroid status. In particular, the impact of PLA2G2A on the brown adipose tissue (BAT) thermogenic gene expression was explored. We induced hypothyroidism in C57BL/6 and PLA2G2A-overexpressing (IIA+) mice over a 10 wk period or treated them with thyroid hormone (T3) for 5 wk. There were no significant changes in PLA2G2A abundance in response to thyroid status. The energy expenditure of hypothyroid IIA+ mice did not increase; however, the energy expenditure, substrate utilization, insulin sensitivity, and glucose tolerance were all elevated in the IIA+ mice given T3. Moreover, white adipocytes from IIA+ mice were much more prone to "beiging," including increased expression of brown adipose thermogenic markers such as uncoupling protein 1 (UCP1), PR domain containing 16, and early B cell factor 2. Finally, the BAT of IIA+ mice had increased UCP1 and other proteins indicative of mitochondrial uncoupling and nonshivering adaptive thermogenesis. These data reveal a novel role for PLA2G2A on adipose tissue thermogenesis depending on thyroid status.-Kuefner, M. S., Deng, X., Stephenson, E. J., Pham, K., Park, E. A. Secretory phospholipase A2 group IIA enhances the metabolic rate and increases glucose utilization in response to thyroid hormone.

Writing The History of the Sevarambians in the 1670s, the Huguenot Denis Veiras borrowed many ideas from Garcilaso de la Vega, also known as El Inca, whose Royal Commentaries of the Incas was published in 1609. Both works describe the history of an empire and justify it on the ground that it brought peace and unity. While Garcilaso’s book purported to be a history, his selection of facts reflected his goal of improving the treatment of the Incas by the Spanish. Veiras’s story also claimed to be a history, but it was transparently a fiction, even to the point of lifting many elements from Garcilaso’s book. What both works equally emphasized was that empires could aim at, and could be justified by, the benefits they provided their subjects. Both tell stories of benevolent and paternalistic rulers who founded nearly ideal societies in the countries they conquered. These were models of empire for peace and unity rather than merely promoting toleration of differences or concord among differing parties...

Background Diabetic cardiomyopathy develops in insulin-dependent diabetic patients who have no hypertension, cardiac hypertrophy or vascular disease. Diabetes increases cardiac fatty acid oxidation, but cardiac hypertrophy limits fatty acid oxidation. Here we examined effects of diabetes on gene expression in rat hearts. Methods We used oligonucleotide microarrays to examine effects of insulindependent diabetes in the rat heart. RTQ PCR confirmed results of microarrays. Specific antibodies were used to examine changes in the mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase 2 (HMGCS2). Results A surprising result of diabetes was increased mRNA encoding all enzymes of the ketone body synthesis pathway. Increased mRNA expression for these enzymes was confirmed by RTQ PCR. The mRNA encoding HMGCS2, the rate-controlling enzyme, was 27 times greater in diabetic hearts. Total HMGCS2 protein increased 8-fold in diabetic hearts, but no difference was found in HMGCS2 protein in control vs. diabetic liver. Conclusions Insulin-dependent diabetes induced the enzymes of ketone body synthesis in the heart, including HMGCS2, as well as increasing enzymes of fatty acid oxidation. General significance The mammalian heart does not export ketone bodies to other tissues, but rather is a major consumer of ketone bodies. Induction of HMGCS2, which is normally expressed only in the fetal and newborn heart, may indicate an adaptation by the heart to combat “metabolic inflexibility” by shifting the flux of excess intramitochondrial acetyl-CoA derived from elevated fatty acid oxidation into ketone bodies, liberating free CoA to balance the acetyl-CoA/CoA ratio in favor of increased glucose oxidation through the pyruvate dehydrogenase complex.

Background: Continuous glucose monitoring (CGM) is an emerging technology that provides real-time interstitial glucose levels through a sensor with a thin filament inserted under the skin. It is customary for patients to rotate sensor application sites between arms to minimize skin irritation. However, the degree of inter-arm differences with CGM technology remains unknown. Materials and Methods: Self-proclaimed right-handed (n=5) and left-handed (n=5) subjects, regardless of concurrent comorbidities, were enrolled for CGM. A FreeStyle Libre Pro Flash Glucose Monitoring System sensor was simultaneously placed on each arm for all subjects. The sensors were worn for a maximum of 14 days with measurements taken every 15 minutes. Muscle mass and body fat analysis was conducted using a multi-frequency segmental body composition analyzer. Glucose levels from the right and left arms were time-matched with the first 12 hours eliminated from analysis. Results: A total of 9830 paired glucose levels were included for analysis. Glucose levels were outside the euglycemic range (70-140 mg/dL) for 14.5% of the time in the right arm compared to 20.0% in the left arm (P10 mg/dL, >20 mg/dL, and >30 mg/dL, for 19.4%, 3.4%, and 0.32% of the time, respectively. The mean glucose level in the right arm was higher than the left arm by 3.75 mg/dL [SD, 8.51 mg/dL] in right-handed subjects, and by 3.84 mg/dL [SD, 7.09 mg/dL] in left-handed subjects (P=0.54). Conclusion: Time in euglycemic range could significantly differ based on arm selection when using a CGM. While the absolute difference in glucose levels between arms appears small, this degree of variability would have significant implications for clinical trial design using CGM technology. Arm dominance does not explain the inter-arm glucose level discordance. Disclosure N. Kim: None. K. Pham: None. A. Shek: None. J.J. Lim: Employee; Self; Genentech, Inc. Stock/Shareholder; Self; F. Hoffmann-La Roche Ltd. S.A. Shah: None. Funding University of the Pacific

We propose the use of projection mapping as a prototyping tool to create an experimentation environment to design, evaluate, and control immersion experience in future autonomous vehicles. As the first step, we conducted expert interviews with professionals in the automotive industry to understand the general implications of prototyping tools in future mobility solution development and their usefulness in concept test settings. The interview results reveal that projection mapping is one popular prototyping method for automotive professionals to demonstrate immersive future user scenarios. The paper includes additional insights from the interviews and current work-in-progress.

Molecular Mechanics Poisson-Boltzmann Surface Area (MMPBSA) methods have become widely adopted in estimating protein-ligand binding affinities due to their efficiency and high correlation with experiment. Here different computational alternatives were investigated to assess their impact to the agreement of MMPBSA calculations with experiment. Seven receptor families with both high-quality crystal structures and binding affinities were selected. First the performance of nonpolar solvation models was studied and it was found that the modern approach that separately models hydrophobic and dispersion interactions dramatically reduces RMSD's of computed relative binding affinities. The numerical setup of the Poisson-Boltzmann methods was analyzed next. The data shows that the impact of grid spacing to the quality of MMPBSA calculations is small: the numerical error at the grid spacing of 0.5 A is already small enough to be negligible. The impact of different atomic radius sets and different molecular surface definitions was further analyzed and weak influences were found on the agreement with experiment. The influence of solute dielectric constant was also analyzed: a higher dielectric constant generally improves the overall agreement with experiment, especially for highly charged binding pockets. The data also showed that the converged simulations caused slight reduction in the agreement with experiment. Finally the direction of estimating absolute binding free energies was briefly explored. Upon correction of the binding-induced rearrangement free energy and the binding entropy lost, the errors in absolute binding affinities were also reduced dramatically when the modern nonpolar solvent model was used, although further developments were apparently necessary to further improve the MMPBSA methods. © 2016 Wiley Periodicals, Inc.

In this paper we examine the response of the magnetosphere-ionopshere (M-I) system to a transient northward excursion in the interplanetary magnetic field (IMF) using the Lyon-Fedder-Mobarry (LFM) global MHD simulation. The simulated IMF transitions hold from a steady southward IMF to a steady northward IMF before suddenly transitioning back to southward IMF after 20 min. Once the IMF returns southward, the M-I system is in a state of reduced energy dissipation for approximately an hour as it reconfigures back into a standard southward IMF configuration. We find that the northward IMF excursion affects both the viscous and reconnection interactions with the solar wind. The flow of plasma in the magnetosphere is significantly disrupted by the reconnection cycle under northward IMF. This reduce the transfer of mechanical energy from the solar wind due to the viscous interaction, and the magnetosphere-ionosphere system is in a mixed topological configuration containing elements produced by both of southward IMF reconnection and the Dungey cycle, as well as northward IMF reconnection and the presence of reverse cell convection at high latitudes. The effects of the transient northward IMF must be completely cleared out before the system can return to an optimal state of energy transfer characteristic of steady southward IMF. As a result, a simple 20 min excursion of northward IMF can put the magnetosphere-ionosphere system into a reduced state of coupling to the solar wind for some time following the return to steady southward IMF; for LFM we saw a reduced state lasting an hour

The aim of this study was to develop a nanotechnology to formulate a fixed-dose combination of poorly water-soluble drugs in a children-friendly, flexible solid dosage form. For diseases like HIV, pediatric patients are taking multiple drugs for effective treatments. Fixed-dose combinations could reduce pill burdens and costs as well as improving patient adherence. However, development of fixed-dose combinations of poorly water-soluble drugs for pediatric formulations is very challenging. We discovered a novel nanotechnology that produced in situ self-assembly nanoparticles (ISNPs) when the ISNP granules were introduced to water. In this study, antiretroviral drug granules, including lopinavir (LPV) ISNP granules and a fixed-dose combination of LPV/ritonavir (RTV) ISNP granules, were prepared using the ISNP nanotechnology, which spontaneously produced drug-loaded ISNPs in contact with water. Drug-loaded ISNPs had particle size less than 158nm with mono-dispersed distribution, over 95% entrapment efficiency for both LPV and RTV and stability over 8h in simulated physiological conditions. Drug-loaded ISNP granules with about 16% of LPV and 4% of RTV were palatable and stable at room temperature over 6months. Furthermore, LPV/RTV ISNP granules displayed a 2.56-fold increase in bioavailability and significantly increased LPV concentrations in tested tissues, especially in HIV sanctuary sites, as compared to the commercial LPV/RTV tablet (Kaletra®) in rats. Overall, the results demonstrated that the novel ISNP nanotechnology is a promising platform to manufacture palatable, "heat" stable, and flexible pediatric granules for fixed-dose combinations that can be used as sachets and sprinkles. To the best of our knowledge, this is the first report on this kind of novel nanotechnology for pediatric fixed-dose combinations of poorly water-soluble drugs.

Pseudoxanthoma elasticum is a heritable disease caused by ABCC6 deficiency. Patients develop ectopic calcification in skin, eyes, and vascular tissues. ABCC6, primarily found in liver and kidneys, mediates the cellular efflux of ATP, which is rapidly converted into inorganic pyrophosphate (PPi), a potent inhibitor of calcification. Pseudoxanthoma elasticum patients and Abcc6–/– mice display reduced PPi levels in plasma and peripheral tissues. Pseudoxanthoma elasticum is currently incurable, although some palliative treatments exist. In recent years, we have successfully developed therapeutic methodologies to compensate the PPi deficit in animal models and humans. Here, we inadvertently discovered that modulating dietary PPi can also be an effective approach to reducing calcification in Abcc6–/– mice. Our findings were prompted by a change in institutional rodent diet. The new chow was enriched in PPi, which increased plasma PPi, and significantly reduced mineralization in Abcc6–/– mice. We also found that dietary PPi is readily absorbed in humans. Our results suggest that the consumption of food naturally or artificially enriched in PPi represents a possible intervention to mitigate calcification progression in pseudoxanthoma elasticum, that dietary preferences of patients may explain pseudoxanthoma elasticum heterogeneous manifestations, and that animal chow has the potential to influence data reproducibility.

Secretory phospholipase A

Relativistic electron flux in the radiation belt can drop by orders of magnitude within the timespan of hours. In this study, we used the drift-diffusion model that includes azimuthal drift and pitch angle diffusion of electrons to simulate low-altitude electron distribution observed by POES/MetOp satellites for rapid radiation belt electron dropout event occurring on May 1, 2013. The event shows fast dropout of MeV energy electrons at L>4 over a few hours, observed by the Van Allen Probes mission. By simulating the electron distributions observed by multiple POES satellites, we resolve the precipitation loss with both high spatial and temporal resolution and a range of energies. We estimate the pitch angle diffusion coefficients as a function of energy, pitch angle, and L-shell, and calculate corresponding electron lifetimes during the event. The simulation results show fast electron precipitation loss at L>4 during the electron dropout, with estimated electron lifetimes on the order of half an hour for MeV energies. The electron loss rate show strong energy dependence with faster loss at higher energies, which suggest that this dropout event is dominated by quick and localized scattering process that prefers higher energy electrons. The improved temporal and spatial resolution of electron precipitation rates provided by multiple low-altitude observations can resolve fast-varying electron loss during rapid electron dropouts (over a few hours), which occur too fast for a single low-altitude satellite. The capability of estimating the fast-varying electron lifetimes during rapid dropout events is an important step in improving radiation belt model accuracy.

In this study we examine the recovery of relativistic radiation belt electrons on November 15-16, 2014, after a previous reduction in the electron flux resulting from the passage of a Corotating Interaction Region (CIR). Following the CIR, there was a period of high-speed streams characterized by large, nonlinear fluctuations in the interplanetary magnetic field (IMF) components. However, the outer radiation belt electron flux remained at a low level for several days before it increased in two major steps. The first increase is associated with the IMF background field turning from slightly northward on average, to slightly southward on average. The second major increase is associated with an increase in the solar wind velocity during a period of southward average IMF background field. We present evidence that when the IMF Bz is negative on average, the whistler mode chorus wave power is enhanced in the outer radiation belt, and the amplification of magnetic integrated power spectral density in the ULF frequency range, in the nightside magnetosphere, is more efficient as compared to cases in which the mean IMF Bz is positive. Preliminary analysis of the time evolution of phase space density radial profiles did not provide conclusive evidence on which electron acceleration mechanism is the dominant. We argue that the acceleration of radiation belt electrons requires (i) a seed population of keV electrons injected into the inner magnetosphere by substorms, and both (ii) enhanced whistler mode chorus waves activity as well as (iii) large-amplitude MHD waves.

This paper describes a sophomore-level ECE course that bridges the gap between the maker movement and typical engineering design courses. This course incorporates the practical skills of fabrication, assembly, and hardware integration found in makerspaces but deepens the perspective from one of getting it to work to designing it to work well and efficiently. This paper discusses mastery-based education in practical skills, an open-ended student-defined design project, and a logistics model that incorporates support staff as partners in the course. The relationship between this course and an ECE-themed makerspace is also discussed.

Soft tissue calcification occurs in several common acquired pathologies, such as diabetes and hypercholesterolemia, or can result from genetic disorders. ABCC6, a transmembrane transporter primarily expressed in liver and kidneys, initiates a molecular pathway inhibiting ectopic calcification. ABCC6 facilitates the cellular efflux of ATP, which is rapidly converted into pyrophosphate (PPi), a major calcification inhibitor. Heritable mutations in ABCC6 underlie the incurable calcification disorder pseudoxanthoma elasticum and some cases of generalized arterial calcification of infancy. Herein, we determined that the administration of PPi and the bisphosphonate etidronate to Abcc6 −/− mice fully inhibited the acute dystrophic cardiac calcification phenotype, whereas alendronate had no significant effect. We also found that daily injection of PPi to Abcc6 −/− mice over several months prevented the development of pseudoxanthoma elasticum–like spontaneous calcification, but failed to reverse already established lesions. Furthermore, we found that the expression of low amounts of the human ABCC6 in liver of transgenic Abcc6 −/− mice, resulting in only a 27% increase in plasma PPi levels, led to a major reduction in acute and chronic calcification phenotypes. This proof-of-concept study shows that the development of both acute and chronic calcification associated with ABCC6 deficiency can be prevented by compensating PPi deficits, even partially. Our work indicates that PPi substitution represents a promising strategy to treat ABCC6-dependent calcification disorders.

The general view is that the response of the magnetosphere-ionosphere system to a complex, variable solar wind input will be a complicated and nonlinear function of that input. We investigate this question using a global MHD code to simulate the interaction and determine the responses of the system to isolated aspects of the solar wind input. We present evidence from the simulations that the solar wind-geospace interaction can be linearly decomposed into component merging interactions for interplanetary magnetic field (IMF) By separate from Bz and a separate viscous interaction. One can run the global simulation (in our case, the Lyon-Fedder-Mobarry code) using just the solar wind plasma and Bz time series, do a second simulation using just the solar wind plasma and By time series, add the results of the two simulation outputs, then subtract the output from a simulation done with only the plasma input and no magnetic field, since the sum of the By and Bz runs has two viscous interactions (one for each run), and get an output that is very close to the result of a single run using the entire IMF merging field (By and Bz) along with the plasma time series. This demonstrates that the components of merging and viscous interactions between the solar wind and geospace are linearly separable to a very large degree.

Background The aim of this study was to determine the minimum effective volume of lidocaine 1.5% with epinephrine 5 μg/mL in 90% of patients (MEV90) for double-injection ultrasound-guided axillary block (AXB). Methods All subjects received a double-injection ultrasound-guided AXB with lidocaine 1.5% and epinephrine 5 μg/mL. A 17-gauge, 8-cm Tuohy needle was initially advanced until its tip was positioned next to the musculocutaneous nerve. Volume assignment was carried out using a biased coin design up-and-down sequential method, where the volume of local anesthetic administered to each patient depended on the response of the previous one. In case of failure, the next subject received a higher volume (defined as the previous volume with an increment of 1.0 mL). If the previous patient had a successful block, the next subject was randomized to a lower volume (defined as the previous volume with a decrement of 1.0 mL), with a probability of b = 0.11, or the same volume, with a probability of 1 − b = 0.89. After injection of the musculocutaneous nerve, the needle was redirected toward the dorsal aspect of the axillary artery. For this second injection, volume assignment was carried out in a similar fashion; however, volume increments/decrements were 3.0 instead of 1.0 mL. Using a composite scale encompassing sensory and motor block, success was defined, at 30 minutes, as a composite score of 4 points (out of 4 points), and 10 points (out of 12 points) for the musculocutaneous and perivascular injection, respectively. Patients undergoing surgery of the forearm, wrist, or hand were prospectively enrolled until 45 successful musculocutaneous blocks or 45 successful perivascular injections were obtained. Results Fifty patients were included in the study. Using isotonic regression and bootstrap confidence interval (CI), the MEV90 was estimated to be 5.5 mL (95% CI, 3.0–6.7 mL) and 23.5 mL (95% CI, 23.1–23.9 mL) for the musculocutaneous and perivascular injection, respectively. Conclusions For double-injection ultrasound-guided AXB, the MEV90 of lidocaine 1.5% with epinephrine 5 μg/mL is 5.5 and 23.5 mL for the musculocutaneous nerve and perivascular injection, respectively. Further dose-finding studies are required for other concentrations of lidocaine, other local anesthetic agents, and other techniques for ultrasound-guided AXB.

Shujie Guo,1 Kevin Pham,2 Diana Li,2 Scott R Penzak,3 Xiaowei Dong2 1State Key Laboratory of Medical Genomics, Shanghai Key Laboratory of Hypertension, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 2Department of Pharmaceutical Sciences, 3Department of Pharmacotherapy, University of North Texas Health Science Center, Fort Worth, TX, USA Purpose: The purpose of this study was to develop a novel lipid-based nanotechnology to formulate poorly water-soluble drugs in oral solid granules to improve stability, palatability, and bioavailability. Materials and methods: In one method, we prepared ritonavir (RTV) nanoparticles (NPs) by a microemulsion-precursor method and then converted the RTV NPs to solid granules by wet granulation to produce RTV NP-containing granules. In the other innovative method, we did not use water in the formulation preparation, and discovered novel in situ self-assembly nanoparticles (ISNPs). We prepared RTV ISNP granules that did not initially contain NPs, but spontaneously produced RTV ISNPs when the granules were introduced to water with gentle agitation. We fully characterized these RTV nanoformulations. We also used rats to test the bioavailability of RTV ISNP granules. Finally, an Astree electronic tongue was used to assess the taste of the RTV ISNP granules. Results: RTV NP-containing granules only had about 1% drug loading of RTV in the solid granules. In contrast, RTV ISNP granules achieved over 16% drug loading and were stable at room temperature over 24 weeks. RTV ISNPs had particle size between 160 nm and 300 nm with narrow size distribution. RTV ISNPs were stable in simulated gastric fluid for 2 hours and in simulated intestinal fluid for another 6 hours. The data from the electronic tongue showed that the RTV ISNP granules were similar in taste to blank ISNP granules, but were much different from RTV solution. RTV ISNP granules increased RTV bioavailability over 2.5-fold compared to RTV solution. Conclusion: We successfully discovered and developed novel ISNPs to manufacture RTV ISNP granules that were reconstitutable, stable, and palatable, and improved RTV bioavailability. The novel ISNP nanotechnology is a platform to manufacture oral solid dosage forms for poorly water-soluble drugs, especially for pediatric formulation development. Keywords: ritonavir, pediatric formulation, taste, pharmacokinetics, lipid formulation, drug loading

The Whole Heliosphere Interval (WHI), comprising March 20–April 16, 2008 (DOY 80–107), is a single Carrington Rotation (2068) designated for intense study through observations and simulations. We used solar wind data from the WHI to run the Coupled Magnetosphere–Ionosphere–Thermosphere (CMIT) and stand-alone Lyon–Fedder–Mobarry (LFM) models. The LFM model was also run with the WHI solar wind plasma parameters but with zero interplanetary magnetic field (IMF). With no IMF, we expect that the cross-polar cap potential (CPCP) is due entirely to the viscous interaction. Comparing the LFM runs with and without the IMF, we found that during strong driving with southward IMF B z , the viscous potential could be a significant fraction of the total CPCP. During times of northward IMF B z , the CPCP was generally lower than the CPCP value from the IMF=0 run. LFM tends to produce high polar cap potentials, but by using the Bruntz et al. (2012) viscous potential formula ( Φ V = μn 0.439 V 1.33 , where μ =0.00431) and the IMF=0 LFM run, we calculated a scaling factor γ =1.54, which can be used to scale the LFM CPCP during the WHI down to realistic values. The Newell et al. (2008) viscous merging term can similarly be used to predict the viscous potential using the formula: Φ V = νn 1/2 V 2 , where the value ν =6.39×10 −5 was also found using the zero IMF run. Both formulas were found to perform better when V (solar wind)= V x , rather than V total , yielding similar, accurate predictions of the LFM viscous potential, with R 2 >0.91 for both formulas. The γ factor was also used to scale down the LFM CPCP from the full solar wind run, with most of the resultant values matching the CPCP from the Weimer05 model well, even though γ was derived independent of the Weimer05 model or the full LFM data. We interpret this to be an indication that the conductivity model in LFM is producing values that are too low, thus elevating the CPCP values.

In this paper we examine the role of dayside merging between the interplanetary magnetic field (IMF) and the geomagnetic field in the generation of the polar cap potential in the ionosphere during the Whole Heliospheric Interval using the Coupled Magnetosphere Ionosphere Thermosphere (CMIT) and Lyon–Fedder–Mobarry (LFM) global simulations of the geospace system from the Center for Integrated Space Weather Modeling (CISM). We isolate the portion of the total ionospheric potential due to the viscous interaction by simulating the interval with a zero IMF, but with the same solar wind plasma conditions. For southward IMF, the cross polar cap potential is the sum of the merging potential and the viscous potential, so we can determine the merging potential by subtracting the viscous potential from the total potential. From the dependence of the merging potential on southward IMF we calculate a geoeffective length of 5 R E . For northward IMF the situation is more complicated since the cross polar cap potential, defined as the peak to peak potential, will be almost always either the value of the viscous potential or of the merging potential, whichever is larger. We find that during periods of northward IMF the cross polar cap potential can be less than what the viscous interaction would produce with no IMF present. This means that the viscous interaction is weakened by the cycle of merging and reconnection for northward IMF. Our results also indicate that current representations of merging rates or electric fields are flawed in the manner in which they describe northward IMF. Typical representations simply produce a weak reconnection rate when the IMF is northward that adds to the viscous potential to create a cross polar cap potential that is larger than the viscous potential, whereas the effect of merging for northward IMF reduces the viscous interaction so that the cross polar cap potential for moderate northward IMF values is smaller than the value that would be expected from solar wind plasma conditions of the viscous potential in isolation.

Background This prospective, randomized, observer-blinded study compared double-, triple-, and quadruple-injection ultrasound (US)–guided axillary brachial plexus block (AXB) for upper-extremity surgery. Methods One hundred twenty patients were randomly allocated to receive a double- (n = 40), triple- (n = 40), or quadruple-injection (n = 40) US-guided AXB. The local anesthetic agent (lidocaine 1.5% with epinephrine 5 μg/mL) and total volume (35 mL) were identical in all subjects. For all 3 groups, the musculocutaneous nerve was identified and anesthetized first. Subsequently, a perivascular technique was performed. Lidocaine was deposited at the 6-o’clock position of the axillary artery for the 2-injection group. For the 3- and 4-injection groups, injections were carried out at the 12-/6-o’clock and 2-/10-/6-o’clock positions, respectively. During the performance of the block, the performance time, number of needle passes, and complications (vascular puncture, paresthesia) were recorded. Subsequently, a blinded observer assessed the onset time, block-related pain scores, and success rate (surgical anesthesia). The main outcome variable was the total anesthesia-related time (sum of performance and onset times). Results No differences were observed among the 3 groups in terms of total anesthesia-related time (29.2–31.4 mins), success rate (90.0%–97.5%), block-related pain scores, vascular puncture, and paresthesia. Compared with its 3- and 4-injection counterparts, the double-injection technique required fewer needle passes (4.0 ± 1.6 vs 5.2–6.0 ± 1.7–2.8; both P ⩽ 0.001). Conclusions Double-, triple-, and quadruple-injection US-guided perivascular AXB result in comparable success rates and total anesthesia-related times. Because it requires fewer needle passes, the double-injection technique provides a simple alternative for US-guided AXB.

Obesity is a chronic condition resulting from a long-term pattern of poor diet and lifestyle. Long-term consumption of high-fat diet (HFD) leads to persistent activation and leptin resistance in AgRP neurons in the arcuate nucleus of the hypothalamus (ARH). Here, for the first time, we demonstrate acute effects of HFD on AgRP neuronal excitability and highlight a critical role for diet composition. In parallel with our earlier finding in obese, long-term HFD mice, we found that even brief HFD feeding results in persistent activation of ARH AgRP neurons. However, unlike long-term HFD-fed mice, AgRP neurons from short-term HFD-fed mice were still leptin-sensitive, indicating that the development of leptin-insensitivity is not a prerequisite for the increased firing rate of AgRP neurons. To distinguish between diet composition, caloric intake and body weight, we compared acute and long-term effects of HFD and CD in pair-fed mice on AgRP neuronal spiking. HFD consumption in pair-fed mice resulted in a significant increase in AgRP neuronal spiking despite controls for weight gain and caloric intake. Taken together, our results suggest that diet composition may be more important than either calorie intake or body weight for electrically remodeling arcuate AgRP/NPY neurons.

Background: This prospective, randomized, observer-blinded trial compared a subepineural sciatic injection at the neural bifurcation (SUB group) and separate postbifurcation injections around the tibial and peroneal nerves. Methods: Ultrasound-guided posterior popliteal sciatic nerve block was carried out in 50 patients. In the group that had separate postbifurcation injections around the tibial and peroneal nerves, the volume of local anesthetic (LA) (30 mL of lidocaine 1%-bupivacaine 0.25%-epinephrine 5 μg/mL) was divided equally between the tibial and peroneal nerves. In the SUB group, the 2 divisions were identified exactly at the neural bifurcation. In this location, both nerves can still be found inside a common epineural sheath. The entire volume of LA was injected between the 2 branches, inside the common sheath. A blinded observer recorded the success rate (complete sensory block at 30 mins) and onset time. The performance time, number of needle passes, and adverse events were also recorded. Total anesthesia-related time was defined as the sum of performance and onset times. Results: Compared with targeted injections around the tibial and peroneal divisions, a subepineural injection resulted in a higher success rate (84% vs 56%; P = 0.032) as well as improved efficiency (decreased performance/onset/total anesthesia-related times and fewer needle passes; all P ≤ 0.028). In the SUB group, we observed no instance of neural swelling. In 3 subjects randomized to separate injections, sonographic swelling of the tibial nerve occurred after the injection of 2 mL of LA. The needle was carefully withdrawn, and the injection completed uneventfully. In 45 patients, follow-up 1 week after the surgery revealed no sensory or motor deficit. Five subjects were lost to follow-up. Conclusions: Compared with separate injections around the tibial and peroneal divisions, a single subepineural injection at the neural bifurcation provides a higher success rate and requires shorter performance, onset, and total anesthesia-related times. Further studies are required to validate the safety of the subepineural technique.

The photoproduction of the Λ 0 and K + from circularly polarized photons on protons is discussed in a simple quark model; we compare the results to experiments.

Obesity is an independent risk factor for troublesome activity-related dyspnea. The mechanisms of increased exertional dyspnea in obesity remain poorly understood and represented the primary focus of our study. To this end, ventilation (VE), breathing pattern, dynamic operating lung volume, diaphragm EMG activity expressed as a percentage of maximum (EMGdi%max; an index measure of neural respiratory drive) and dyspnea responses to symptom-limited incremental cycle exercise testing were compared between 30 obese (OB; 15M:15W; mean±SE BMI=33.6±0.8 kg/m2; 43±1% fat mass; 137±3% ideal body mass) and 30 non-obese (NOB; 15M:15W; BMI=21.8±0.3 kg/m2; 28±1% fat mass; 89±1% ideal body mass) adults aged 18-40 yrs. After adjusting for differences in lean body mass (OB, 56±2 vs. NOB, 46±2 kg), VE, breathing frequency, EMGdi%max and dyspnea were higher at any standardized submaximal work rate during exercise in OB vs. NOB. Mean values of inspiratory capacity (IC) and inspiratory reserve volume (IRV) were higher (by ∼260 mL and ∼400 mL, respectively) at rest and at any VE during exercise in OB vs. NOB. Interestingly, EMGdi%max-IRV and dyspnea-IRV relationships were parallel shifted to the left during exercise in OB vs. NOB. By contrast, EMGdi%max-VE, dyspnea-VEand dyspnea-EMGdi%max relationships were similar throughout much of exercise in OB vs. NOB. In conclusion, mechanical adaptations of the respiratory system, including recruitment of resting (pre-exercise) IC and IRV, helped to preserve EMGdi%max-VE relationships during exercise in OB vs. NOB. Under these circumstances, the increased perception of exertional dyspnea in OB likely reflected the awareness of increased neural respiratory drive.

Non-steroidal anti-inflammatory drugs (NSAIDs) and selective cyclooxygenase-2 inhibitors (Coxibs) are commonly used for minor pain treatment and chronically in the management of rheumatoid arthritis and osteoarthritis. Three areas of safety concerns are shared by both groups of drugs: Gastrointestinal complications (upper gastrointestinal bleeding, perforations or obstruction), cardiovascular safety (mainly myocardial infarction) and renal safety (acute renal failure, hypertension and electrolyte abnormalities). The incidence of renal complications may be increased two-fold with NSAIDs or coxibs, and there is no evidence for a major difference between the two groups of drugs. Coxibs are clearly associated with improved gastrointestinal safety compared to NSAIDs, but this benefit is reduced and may be lost completely with concurrent low-dose aspirin use. In contrast, coxibs may be associated with a greater incidence of cardiovascular complications, mainly myocardial infarction, especially in comparison to certain NSAIDs such as naproxen. Thus, coxibs are not generally safer than NSAIDs. Rather, their long-term use should be customized to individual patients and their intrinsic baseline risks and other medications required in their management.

Background This prospective, randomized, observer-blinded study compared 3 combinations of volume and concentration using the same total dose of lidocaine for ultrasound-guided infraclavicular block. Methods Ninety patients were randomized to 1 of 3 combinations of volume and concentration for lidocaine: (1) 52.5 mL of lidocaine 1%, (2) 35 mL of lidocaine 1.5%, and (3) 26.25 mL of lidocaine 2%. In all 3 groups, the total dose administered (525 mg) was the same. In addition, epinephrine 5 fg/mL was used in all subjects. The main outcome variable was onset time. The performance time, number of needle passes, block-related pain scores, success rate (surgical anesthesia), and the incidence of vascular puncture and paresthesia were also recorded. The total anesthesia-related time was defined as the sum of the performance and onset times. Results The onset times, which were 18.8 ± 5.6 minutes (95% confidence interval [CI], 16.4–21.1 minutes), 20.7 ± 7.0 minutes (95% CI, 18.0–23.5 minutes), and 21.7 ± 6.0 minutes (95% CI, 19.1–24.2 minutes) for the 1%, 1.5%, and 2% groups, respectively, were not statistically different. Furthermore, the performance times (4.4–4.7 minutes), total anesthesia-related times (23.7–26.3 minutes), and rates of surgical anesthesia (90.0%–96.7%) were comparable among the 3 groups. The number of needle passes and procedural discomfort, as well as the incidence of paresthesia and vascular puncture, were also similar. There were minor differences in the patterns of block for individual nerves. In terms of sensory block, compared with the 2% group, more patients in the 1.5% group displayed a complete block of the ulnar and radial nerves at 10 and 20 minutes, respectively. In terms of motor block, the 2% group yielded the lowest of rate of complete block of the musculocutaneous nerve from 15 minutes onward. Conclusions Using an identical dose (525 mg) of adrenalized lidocaine for ultrasound-guided infraclavicular block, we found no differences in onset time among 3 commonly used concentrations (1%, 1.5%, and 2%). Further studies are required to determine the optimal combination of volume and concentration of lidocaine for other ultrasound-guided approaches to the brachial plexus.

BACKGROUND: In this prospective, randomized, observer-blinded trial, we compared ultrasound-guided subparaneural popliteal sciatic nerve blocks performed either at or proximal to the neural bifurcation (B). We hypothesized that the total anesthesia-related time (sum of performance and onset times) would be decreased with the prebifurcation (PB) technique. METHODS: Ultrasound-guided posterior popliteal sciatic nerve block was performed in 68 patients. All subjects received an identical volume (30 mL) and mix of local anesthetic agent (1% lidocaine–0.25% bupivacaine–5 µg/mL epinephrine). In the PB group, the local anesthetic solution was deposited at the level of the common sciatic trunk, just distal to the intersection between its circular and elliptical sonographic appearances, inside the paraneural sheath. In the B group, the injection was performed inside the sheath between the tibial and peroneal divisions. A blinded observer recorded the success rate (complete tibial and peroneal sensory block at 30 minutes) and onset time. The performance time, number of needle passes, and adverse events (paresthesia, neural edema) were also recorded. All subjects were contacted 7 days after the surgery to enquire about the presence of persistent numbness or motor deficit. RESULTS: Both techniques resulted in comparable success rates (85%–88%; 95% confidence interval [CI] of the intergroup difference, −14% to 19%) and required similar performance times (8.1 minutes; 95% CI of the difference, −1.65 to 1.71 minutes), onset times (15.0–17.7 minutes; 95% CI of the difference, −7.65 to 2.31 minutes), and total anesthesia-related times (23.4–26.0 minutes; 95% CI of the difference, −7.83 to 2.74 minutes). The number of needle passes and incidence of paresthesia (25%–34%) were also similar between the 2 groups. Sonographic neural swelling was detected in 2 and 3 subjects in the PB and B groups, respectively. In all 5 cases, the needle was carefully withdrawn and the injection completed uneventfully. Patient follow-up 1 week after the surgery revealed 2 patients with residual numbness. In both instances, the latter had resolved by 1 month. CONCLUSION: When local anesthetic is injected inside the paraneural sheath, B and PB posterior popliteal sciatic nerve blocks result in comparable success and total anesthesia-related times. However, in light of the 95% CIs, we cannot exclude the possibility that an intergroup difference of 19% and 7.83 minutes might have gone undetected for success rate and total time, respectively.

BACKGROUND AND OBJECTIVE Lasers are used for caries removal in enamel and dentin, but are currently limited in their ability to remove sound tooth structure. In this study plasma interaction regimes are investigated as the principal factor determining the ablation characteristics. STUDY DESIGN/MATERIALS AND METHODS Three ablation parameters are considered: ablation rates (AR), surface temperatures (ST), and surface morphological characteristics. The three lasers investigated were Er:YSGG with wavelength (WL) of 2.94 mu m and pulse duration (PD) of 250 mu s, Ho:YSGG at 2.1 mu m and 250 mu s and an Nd:YAG with WL of 1.06 mu M and PD of 15ns. RESULTS The highest surface temperatures were observed during Er:YSGG treatment (> 300 degrees C), moderate temperatures with the Ho:YSGG (150 degrees C), and lowest with the Nd:YAG (with highest surface temperature generally lower than 80 degrees C). Ablation rates were also compared and were shown to be highest with the Er:YSGG and Ho:YSGG, and lower with the Nd:YAG (< 3 mu m). In all systems, efficient ablation was observed only in the presence of plasma. In spite of their different wavelengths, for similar spot sizes, energy, and pulse duration, ablation rates of Ho:YSGG and Er:YSGG were found to be comparable. These were an order of magnitude larger than the ablation rates observed with the nanosecond system. CONCLUSION Possible explanation for these observations is given in terms of plasma characteristics.

A tissue equivalent phantom (TEQ) was designed and constructed for in vivo biocompatible communication systems operating from 902-928 MHZ (Industrial, Scientific and Medical (ISM) band). The tissue equivalent phantom was designed by first noting the permittivity and conductivity of various tissues in the human torso using the FCC website http://www.fcc.gov/oet/rfsafety/dielectric.html, then by mixing the appropriate amounts of TX-151 (a polysaccharide gel), distilled water, sodium chloride and sucrose until the different regions of the phantom matched the parameters of the human torso Initial values were recorded based on previous work at lower frequencies and determined empirically at 915MHz. Computer modeling studies of human tissue were performed over the 902-928MHz band using a finite difference time domain computer modeling program (xFDTD, RECOM). Comparative analysis was conducted to determine the performance of the phantom. The phantom allows for testing and evaluation of very small antenna devices designed for in vivo diagnostics and monitoring.

We report on a pilot study demonstrating a proof of concept for the passive delivery of nanoshells to an orthotopic tumor where they induce a local, confined therapeutic response distinct from that of normal brain resulting in the photo-thermal ablation of canine Transmissible Venereal Tumor (cTVT) in a canine brain model. cTVT fragments grown in SCID mice were successfully inoculated in the parietal lobe of immuno-suppressed, mixed-breed hound dogs. A single dose of near-infrared absorbing, 150 nm nanoshells was infused intravenously and allowed time to passively accumulate in the intracranial tumors which served as a proxy for an orthotopic brain metastasis. The nanoshells accumulated within the intracranial cTVT suggesting that its neo-vasculature represented an interruption of the normal blood-brain barrier. Tumors were thermally ablated by percutaneous, optical fiber-delivered, near-infrared radiation using a 3.5 W average, 3-minute laser dose at 808 nm that selectively elevated the temperature of tumor tissue to 65.8±4.1oC. Identical laser doses applied to normal white and gray matter on the contralateral side of the brain yielded sub-lethal temperatures of 48.6±1.1oC. The laser dose was designed to minimize thermal damage to normal brain tissue in the absence of nanoshells and compensate for variability in the accumulation of nanoshells in tumor. Post-mortem histopathology of treated brain sections demonstrated the effectiveness and selectivity of the nanoshell-assisted thermal ablation.

We report on a pilot study showing a proof of concept for the passive delivery of nanoshells to an orthotopic tumor where they induce a local, confined therapeutic response distinct from that of normal brain resulting in the photothermal ablation of canine transmissible venereal tumor (cTVT) in a canine brain model. cTVT fragments grown in severe combined immunodeficient mice were successfully inoculated in the parietal lobe of immunosuppressed, mixed-breed hound dogs. A single dose of near-IR (NIR)–absorbing, 150-nm nanoshells was infused i.v. and allowed time to passively accumulate in the intracranial tumors, which served as a proxy for an orthotopic brain metastasis. The nanoshells accumulated within the intracranial cTVT, suggesting that its neovasculature represented an interruption of the normal blood-brain barrier. Tumors were thermally ablated by percutaneous, optical fiber–delivered, NIR radiation using a 3.5-W average, 3-minute laser dose at 808 nm that selectively elevated the temperature of tumor tissue to 65.8 ± 4.1°C. Identical laser doses applied to normal white and gray matter on the contralateral side of the brain yielded sublethal temperatures of 48.6 ± 1.1°C. The laser dose was designed to minimize thermal damage to normal brain tissue in the absence of nanoshells and compensate for variability in the accumulation of nanoshells in tumor. Postmortem histopathology of treated brain sections showed the effectiveness and selectivity of the nanoshell-assisted thermal ablation. [Cancer Res 2009;69(4):1659–67]

Oral feeding of renal tubular antigen abrogates interstitial nephritis and renal failure in Brown Norway rats. We have examined whether oral feeding of antigen can regulate the expression of autoimmune interstitial nephritis induced by antigen-in-adjuvant (RTA/CFA) immunization of Brown Norway rats. Male rats were divided into six experimental groups: Group I, RTA/CFA immunization alone; Groups II, III, and IV were pretreated with 1mg (Group II), 5mg (Group III), and 25mg (Group IV) of oral tubular antigen every other day for ten days, followed by RTA/CFA immunization; Group V was pretreated with a control antigen, followed by RTA/CFA immunization; and Group VI was immunized with CFA alone. Renal histology, inulin clearance, DTH responses to RTA, and IgG antibody responses to RTA were monitored as endpoints of the study. Our results demonstrated that Group III and IV animals had significantly less severe renal injury, as assessed by inulin clearance and extent of renal cortical involvement by mononuclear cells. Group II and IV animals had suppressed DTH responses, and only Group IV animals had significantly depressed antigen-specific IgG serum titers. Group III animals had neither suppressed DTH responses or IgG titers. We conclude that oral administration of tubular antigen can modulate the intensity of interstitial nephritis produced by immunization, but that the regulatory mechanism is not dependent (at all doses of fed antigen) on suppressed DTH reactivity to RTA or suppressed antigen-specific IgG.