Elizabeth R. Lusczek

Observations of the Askaryan Effect in Ice

We report on observations of coherent, impulsive radio Cherenkov radiation from electromagnetic showers in solid ice. This is the first observation of the Askaryan effect in ice. As part of the complete validation process for the ANITA experiment, we performed an experiment at the Stanford Linear Accelerator Center in June 2006 using a 7.5 metric ton ice target. We measure for the first time the large-scale angular dependence of the radiation pattern, a major factor in determining the solid-angle acceptance of ultrahigh-energy neutrino detectors.

The Antarctic Impulsive Transient Antenna ultra-high energy neutrino detector: Design, performance, and sensitivity for the 2006–2007 balloon flight

Abstract We present a comprehensive report on the experimental details of the Antarctic Impulsive Transient Antenna (ANITA) long-duration balloon payload, including the design philosophy and realization, physics simulations, performance of the instrument during its first Antarctic flight completed in January of 2007, and expectations for the limiting neutrino detection sensitivity.

New Limits on the Ultrahigh Energy Cosmic Neutrino Flux from the ANITA Experiment

We report initial results of the first flight of the Antarctic Impulsive Transient Antenna (ANITA-1) 2006-2007 Long Duration Balloon flight, which searched for evidence of a diffuse flux of cosmic neutrinos above energies of E(nu) approximately 3 x 10(18) eV. ANITA-1 flew for 35 days looking for radio impulses due to the Askaryan effect in neutrino-induced electromagnetic showers within the Antarctic ice sheets. We report here on our initial analysis, which was performed as a blind search of the data. No neutrino candidates are seen, with no detected physics background. We set model-independent limits based on this result. Upper limits derived from our analysis rule out the highest cosmogenic neutrino models. In a background horizontal-polarization channel, we also detect six events consistent with radio impulses from ultrahigh energy extensive air showers.

Observation of ultrahigh-energy cosmic rays with the ANITA balloon-borne radio interferometer

We report the observation of 16 cosmic ray events with a mean energy of 1.5 × 10¹⁹ eV via radio pulses originating from the interaction of the cosmic ray air shower with the Antarctic geomagnetic field, a process known as geosynchrotron emission. We present measurements in the 300-900 MHz range, which are the first self-triggered, first ultrawide band, first far-field, and the highest energy sample of cosmic ray events collected with the radio technique. Their properties are inconsistent with current ground-based geosynchrotron models. The emission is 100% polarized in the plane perpendicular to the projected geomagnetic field. Fourteen events are seen to have a phase inversion due to reflection of the radio beam off the ice surface, and two additional events are seen directly from above the horizon. Based on a likelihood analysis, we estimate angular pointing precision of order 2° for the event arrival directions.

Chronic Alcohol Ingestion Increases Mortality and Organ Injury in a Murine Model of Septic Peritonitis

Background Patients admitted to the intensive care unit with alcohol use disorders have increased morbidity and mortality. The purpose of this study was to determine how chronic alcohol ingestion alters the host response to sepsis in mice. Methods Mice were randomized to receive either alcohol or water for 12 weeks and then subjected to cecal ligation and puncture. Mice were sacrificed 24 hours post-operatively or followed seven days for survival. Results Septic alcohol-fed mice had a significantly higher mortality than septic water-fed mice (74% vs. 41%, p = 0.01). This was associated with worsened gut integrity in alcohol-fed mice with elevated intestinal epithelial apoptosis, decreased crypt proliferation and shortened villus length. Further, alcohol-fed mice had higher intestinal permeability with decreased ZO-1 and occludin protein expression in the intestinal tight junction. The frequency of splenic and bone marrow CD4+ T cells was similar between groups; however, splenic CD4+ T cells in septic alcohol-fed mice had a marked increase in both TNF and IFN-γ production following ex vivo stimulation. Neither the frequency nor function of CD8+ T cells differed between alcohol-fed and water-fed septic mice. NK cells were decreased in both the spleen and bone marrow of alcohol-fed septic mice. Pulmonary myeloperoxidase levels and BAL levels of G-CSF and TFG-β were higher in alcohol-fed mice. Pancreatic metabolomics demonstrated increased acetate, adenosine, xanthine, acetoacetate, 3-hydroxybutyrate and betaine in alcohol-fed mice and decreased cytidine, uracil, fumarate, creatine phosphate, creatine, and choline. Serum and peritoneal cytokines were generally similar between alcohol-fed and water-fed mice, and there were no differences in bacteremia, lung wet to dry weight, or pulmonary, liver or splenic histology. Conclusions When subjected to the same septic insult, mice with chronic alcohol ingestion have increased mortality. Alterations in intestinal integrity, the host immune response, and pancreatic metabolomics may help explain this differential response.

In situ radioglaciological measurements near Taylor Dome, Antarctica and implications for ultra-high energy (UHE) neutrino astronomy

Radiowave detection of the Cherenkov radiation produced by neutrino-ice collisions requires an understanding of the radiofrequency (RF) response of cold polar ice. We herein report on a series of radioglaciological measurements performed approximately 10 km north of Taylor Dome Station, Antarctica from Dec. 6, 2006 - Dec. 16, 2006. Using RF signals broadcast from: a) an englacial discone, submerged to a depth of 100 meters and broadcasting to a surface dual polarization horn receiver, and b) a dual-polarization horn antenna on the surface transmitting signals which reflect off the underlying bed and back up to the surface receiver, we have made time-domain estimates of both the real (index-of-refraction) and imaginary (attenuation length) components of the complex ice dielectric constant. We have also measured the uniformity of ice response along two orthogonal axes in the horizontal plane. We observe a wavespeed asymmetry of order 0.1%, projected onto the vertical propagation axis, consistent with some previous measurements, but somewhat lower than others.

Metabolomics classifies phase of care and identifies risk for mortality in a porcine model of multiple injuries and hemorrhagic shock.

BACKGROUND Early recognition and intervention in hemorrhagic shock is essential to improved outcomes. However, the lack of robust diagnostic tools readily available to identify patients in the field inhibits the ability to provide timely intervention. Therefore, the development of a reliable prognostic indicator, such as a serum biomarker or a metabolic profile, has significant potential to improve far-forward trauma care. In this study, we used metabolomics as a tool to identify a metabolic state associated with the hemorrhagic shock and outcome in our porcine model of multiple injuries, shock, and resuscitation. METHODS Proton nuclear magnetic resonance spectroscopy was used to evaluate serum metabolites from 23 animals that underwent multiple injuries, controlled hemorrhage, and 20 hours of a standard resuscitation protocol. Serum samples were collected from the animals at baseline (before hemorrhage), at shock (after 45 minutes of shock), and at 8 hours of full resuscitation. RESULTS We were able to demonstrate shifts in the metabolome throughout different time points and construct a metabolic profile associated with mortality using partial least squares discriminate analysis. The metabolites most responsible for the classification of hemorrhagic shock in our model serve as markers for ischemia, changes in energy production, and cellular damage. Hemorrhagic shock was characterized by marked increases in tricarboxylic acid cycle intermediates, glycolytic-gluconeogenic by-products, purine-pyrimidine catabolism, and fatty acid oxidation. CONCLUSION The results of this study demonstrate the potential for metabolomics as a tool to classify the metabolic flux, to identify relevant biochemical pathways, and to identify clinically useful biomarkers.

Liver Metabolomic Changes Identify Biochemical Pathways in Hemorrhagic Shock

BACKGROUND Despite ongoing advances in treatment, thousands of patients still die annually from complications due to hemorrhagic shock, a condition causing dramatic physiologic and metabolic changes as cells switch to anaerobic metabolism in response to oxygen deprivation. As the shift from aerobic to anaerobic metabolism occurs in the peripheral tissues during shock, the liver must increase production of endogenous glucose as well as process excess lactate produced in the periphery. This places the liver at the center of metabolic regulation in the body during hemorrhagic shock. Therefore, we hypothesized that liver tissue from pigs during an in vivo model of hemorrhagic shock (n = 6) would reflect resultant metabolic changes. MATERIALS AND METHODS The in vivo model of shock consisted of 45 min of shock followed by 8 h of hypotensive resuscitation (80 mmHg) and subsequent normotensive resuscitation (90 mmHg) ending 48 h after the shock period. Control groups of pigs (n = 3) (1) shock with no resuscitation, and (2) only anesthesia and instrumentation, also were included. Metabolic changes within the liver after shock and during resuscitation were investigated using both proton ((1)H) and phosphorous ((31)P) nuclear magnetic resonance (NMR) spectroscopy. RESULTS Concentrations of glycerylphosphorylcholine (GPC) and glycerylphosphorylethanolamine (GPE) were significantly lower at 8 h after shock, with recovery to baseline by 23 and 48 h after shock. Uridine diphosphate-glucose (UDP-glucose), and phosphoenolpyruvate (PEP) were elevated 23 h after shock. CONCLUSIONS These results indicate that (1)H and (31)P NMR spectroscopy can be used to identify differences in liver metabolites in an in vivo model of hemorrhagic shock, indicating that metabolomic analysis can be used to elucidate biochemical events occurring during this complex disease process.

Urine Metabolomics in Hemorrhagic Shock: Normalization of Urine in the Face of Changing Intravascular Fluid Volume and Perturbations in Metabolism

There are many ways to normalize biofluid metabolomics data to account for changes in dilution, all of which have been thoroughly examined in model systems. Here, urine metabolomics data was examined under relevant physiological conditions obtained from a porcine model of hemorrhagic shock and resuscitation. This includes highly variable intravascular fluid volume and urine output coupled with large perturbations in the abundance of endogenous metabolites. Seven different normalization techniques and raw data were evaluated to determine an appropriate normalization technique in this setting, including spectral post-processing methods and physiological measures of concentration. Relationships between normalization constants for each urine sample were examined, as well as relationships between urinary and serum creatinine concentrations. Principal components analysis was used to examine clustering of metabolomics data. The set of normalization constants associated with each sample were reflective of urine concentration, with a trend toward concentration decreases during late resuscitation timepoints. Urinary creatinine normalized to urine output was most reflective of serum creatinine levels. Principal components analysis showed that urine samples clustered according to experimental timepoint for all normalization methods examined. Little separation was seen in raw data. Urine output-normalized data stands out from the six other normalization methods studied because it is reflective of renal clearance and should be used when comparing urine and serum metabolomics data.

Carbohydrate fed state alters the metabolomic response to hemorrhagic shock and resuscitation in liver

Hemorrhagic shock with injury results in alterations of the metabolic state of an organism, which contribute to organ dysfunction and death. Previous investigations have explored the effects of carbohydrate prefeed in murine models but few in clinically relevant large animal models. We performed carbohydrate prefeed in pigs undergoing simulated polytrauma and hemorrhagic shock with resuscitation to determine if carbohydrate prefeeding if the metabolic response to shock is dependent on fed state. Sixty-four Yorkshire pigs were divided into two experimental groups: fasted (32) and prefed (32). Experimental animals were subjected to a standardized hemorrhagic shock protocol, including pulmonary contusion and liver crush injury. To determine molecular alterations in response to trauma as a result of prefeeding, liver biopsies were obtained at set timepoints throughout the procedure. Fifty-one metabolites were profiled for each sample via proton nuclear magnetic resonance spectroscopy (1H NMR). Partial-Least Squared Discriminant Analysis (PLS-DA) was used to examine clustering of the data with respect to fed state. Cross-validated models separated the fed from fasted animals. Metabolites contributing to the separation have known relationships to alternate carbon energy sources, amino acid metabolism, oxidative stress response, and membrane maintenance. In conclusion, metabolomic techniques allowed identification of an alternate response to shock and resuscitation, dependent upon fed state, through the use of metabolomics.