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Medical and Health Sciences Abstracts:

A Noninvasive Method to Assess Left and Right Ventricular Fractional Area Change in Genetically Altered Mice. MEAGAN GREEN (La Salle University, Philadelphia, PA, 19141) HELENE BENVENISTE (Brookhaven National Laboratory, Upton, NY, 11973)

The techniques which allow a comprehensive assessment of cardiovascular performance in small animals are still limited. The development of a noninvasive cardiac MRI- based method to facilitate the analysis of both right and left ventricular function in a mouse heart is essential in a cardiac study. The use of animals with genetic modifications, which lacks the ability to produce vasointestinal peptide (VIP), and important cardiovascular regulatory factor. The use of these animals with genetic modifications allows for a more precise assessment of cardiovascular failure development. Changes in myocardial VIP concentration or with alteration of physiological responsiveness of VIP receptors have been links to the development of severe cardiovascular disorders, such as myocardial fibrosis, heart failure, cardiomyopathy and pulmonary hypertension. The goal of this study was to compare the left and right ventricle to see if they are both equally involved in the development of cardiomyopathy in VIP-deficient mice. The cardiac imagine was performed in five anesthetized animals using several different Flash_movie sequences in a 9.4T MicroMRI system. Once the images were obtained Amira Imaging software was utilized to make outlines of the left and right ventricular cavities and areas for each ventricle were obtained during different phase of the cardiac cycle. A transactional view through the midpapillary level was used for analysis. Functional ventricular assessment was performed by calculating the fractional area change (FRAC) during systole. Data showed that there was not a significant difference between the left ventricle (53.87 +/- 13.66%) and the right ventricle (52.90 +/- 15.01%) FRAC. Both sides developed significant hypertrophy of the myocardial wall. In summary, the VIP- deficient mouse, the development of cariomyopathy was shown to similarly affect both the left and right ventricular function. We were able to develop a noninvasive method for advanced characterization of cardiac function in the murine model. This will help to facilitate longitudinal study of the heart disease process. The long term goal of this study is to map the development of heart disease.

An Examination of Perseveration in Cocaine Abusers. TANYA LUKASIK (Stony Brook University, Stony Brook, NY, 11794) RITA GOLDSTEIN, PH.D. & PATRICIA WOICIK, PH.D. (Brookhaven National Laboratory, Upton, NY, 11973)

Drug addiction is associated with executive deficits that are typically attributed to dysfunction in prefrontal brain regions (e.g., the ventromedial region of the orbitofrontal cortex and dorsolateral prefrontal cortex). Cocaine-addicted individuals exhibit mild performance deficits on neuropsychological tasks that require set shifting, instead, perseverating on previously rewarded behavior. However, the research reported is inconclusive possibly due to the heterogeneity among cocaine-abusing populations. In the current study, cocaine abusers were compared to healthy control subjects on the Wisconsin Card Sorting Task, (WCST); a classical neuropsychological task that assesses concept formation, cognitive flexibility and set shifting. Cocaine abusers were grouped according to their ability to complete all categories on the WCST (high functioning versus low functioning). Compared to higher functioning cocaine subjects, lower functioning cocaine abusers were associated with more positive urine screens. Lower functioning cocaine subjects also scored lower on indices of general intelligence and traditional indices (total scores) of the WCST as compared to higher functioning cocaine subjects and controls. In contrast, higher functioning cocaine abusers scored similarly to controls on total scores of the WCST, however, an examination of performances at the category level suggests a different pattern of learning, specifically a tendency to perseverate in the first sequence of the task. Results suggest two patterns of executive dysfunction in cocaine abusers; one associated with lower functioning cocaine abusers that is more severe and possibly related to acute withdrawal (recent cocaine use) and another associated with higher functioning cocaine abusers characterized by mild perseverative deficits.

Analysis of Sharps Safety Procedures and Injury Prevention Methods at Lawrence Livermore National Laboratory. NICOLE SADLER (University of California, Davis, CA, 95616) LESLIE HOFHERR (Lawrence Livermore National Laboratory, Livermore, CA, 94550)

Today’s hazardous world demands safe work practices. An employee’s risk of injury and infection increases significantly when he handles sharps. To assess sharps use and compliance with correct safety controls and practices, the author generated a survey form. This form was based on current safety standards and used to conduct face-to-face interviews of Lawrence Livermore National Laboratory (LLNL) personnel who were using biological materials and sharps in research projects. At LLNL, current safety standards are summarized in what is known as the Environmental Safety and Health (ES&H) Manual. Close scrutinization of the ES&H manual confirmed consistency with the current sharps use standards. The Occupational Safety & Health Administration (OSHA) Bloodborne Pathogens Standard mandates that employers maintain a sharps injury log. The survey was designed to determine if any discrepancies between the number of sharps injuries sustained and those reported existed. However, the LLNL sharps injury log was not currently available but will be available in the future, and therefore such comparisons were not performed as part of this analysis. Twenty percent of the facilities using sharps at LLNL were evaluated. During the assessments, almost sixty percent of the labs had an observable sharps safety hazard. These safety breaches fell into one of the following three categories: improper recapping technique, presence of an exposed or improperly discarded sharp, or overfilled sharps container. Nearly twenty percent of the individuals interviewed either had injured himself with a sharp or knew of someone affiliated with his particular lab that had been injured. Seventy-five percent of the reported injuries occurred in a BSL-2 lab. Most researchers at LLNL use scalpels and needles. Half of the researchers reuse their sharps, a practice that should be avoided. The statistical results of the surveys alerted safety personnel to the need for sharps training and further evaluation of sharps use at LLNL.

Analyzing Intensive Care Unit (ICU) and Emergency Room (ER) Unit Records. LAKEISHA MELTON (Texas Southern University, Houston, TX, 77004) JONATHAN YOUNG (Pacific Northwest National Laboratory, Richland, WA, 99352)

By analyzing Intensive Care Unit (ICU) incident reports and Emergency Room (ER) Unit medical records using data analysis, data mining, and cluster analysis, a statistical representation and a data visualization of the analyzed data can support the discovery of complex and unanticipated relationships extant in the data. The primary focus of this project is to identify potential weaknesses and systematic problems throughout the datasets of patient medical records and potential unanticipated process behavior in order to potentially sustain improvements in the reduction of patient medical errors and the enhancement of healthcare facility performance. A tool called IN-SPIRE TM, is used to explore each type of data (incident reports and medical records) individually and thoroughly to find the complex relationships in the records. The analysis tools were also used to analyze clusters of records, categorize and group those records in order to potentially produce data visualizations and statistical representations of the analyzed data.

Detection of Cocaine-induced Cerebral Hemodynamic and Neuronal Function Changes in vivo Using Laser Doppler Flowmetry. MELISSA TULLY (Stony Brook University, Stony Brook, NY, 11794) CONGWU DU (Brookhaven National Laboratory, Upton, NY, 11973)

Cocaine abuse increases the risk of life-threatening neurological complications such as stroke, seizures and transient ischemic attacks. Further, chronic intake leads to long lasting cognitive and behavioral changes. Cocaine has vasoconstrictive properties and also decreases the cerebral metabolism. However, the exact pathophysiological mechanisms underlying cocaine’s neurotoxic effects remains incompletely understood. In this study, Laser-Doppler flowmetry (LDF) was used to characterize the effects of cocaine on the cerebral blood flow (CBF) in the rat brains in vivo and compare these changes with CBF changes elicited in the same animal in response to forepaw electrical stimulation before and after the acute cocaine challenge. The rats were anesthetized, intubated, mechanically ventilated, and catheterized to monitor the physiological parameters. The rats were then positioned in a stereotaxic frame and a craniotomy was preformed above the left somatosensory cortex. The LDF probe was then mounted upon the exposed brain surface in the somatosensory cortex area, and the changes in the local cerebral blood flow (LCBF) along with the changes in the red blood cell concentration and speed were recorded using the LDF. Electrical stimulations were then administered to the right forepaw subcutaneously to induce a neuronal activation in the left somatosensory cortex with the various stimulation frequencies (1, 2, 3, 5& 8Hz). Cocaine (1mg/kg) was then injected via the venous catheter and the series of stimulations was repeated 5 minutes after the injection until a neuronal response was obtained and LCBF was continually recorded during the experiment. Our preliminary results indicate that cocaine has different effects on the amplitude of response to forepaw electrical stimulation depending upon the stimulation frequency. There was a 25% increase in CBF immediately following the cocaine administration. The mean arterial blood pressure (MABP) also increased to 115 mm Hg from a baseline of approximately 95 mm Hg. The CBF as well as the MABP increase induced by cocaine were transient and recovered to baseline 5 minutes and 8 minutes, respectively after cocaine. However, a neurological response was not obtained until 40 min after the injection. After this time had elapsed, cocaine did not appear to affect the neuronal response at a stimulation frequency of 3 Hz. The present results elucidate the time course of cocaine’s acute cerebrovascular and neurological effects and provide a better understanding of the etiology of cocaine-related stroke and transient ischemic attacks.

Developmental Assesment of the D4 Receptor Mice: Part I -Locomotor Activity. NATALIA LONDONO (Stony Brook University, Stony Brook, NY, 11794) DR. PANAYOTIS (PETER) K. THANOS (Brookhaven National Laboratory, Upton, NY, 11973)

Dopamine, a neurotransmitter that regulates cognition, movement, pleasure, and motivation, is related to the physiological and behavioral changes that are important aspects of aging, such as the loss of independence because of the deterioration of motor functions. This study investigated the relationship between locomotor activity and development in dopamine D4 receptors mice that were either single or group housed. Wild-type, Heterozygous, and Knockout D4 mice were used for this experiment (from age 10 - 100 weeks). Group housed mice were provided with an enrichment environment and single housed were in standard conditions. Their locomotor activity was recorded weekly. While the results are still in progress, the study will examine the change (if any) in locomotor activity across D4 genotype and in single versus group housed mice. These results will also examine the interaction of the D4 genotype with environment and locomotor activity. Future experiments will compare these findings in other dopamine receptors in mice.

Effect of Inhibitors on bFGF Signal Transduction Pathways in Human Endothelial Cells. AMANDA VREELAND (State University of New York at Stony Brook, Stony Brook, NY, 11794) LOUIS A. PENA (Brookhaven National Laboratory, Upton, NY, 11973)

Ionizing radiation, such as that used in radiation therapy, causes cells to undergo apoptosis or programmed cell death. Basic Fibroblast Growth Factor (bFGF) has been shown to inhibit irradiated cells from undergoing apoptosis. bFGF promotes cell growth through several signal transduction cascades: Mitogen Activated Protein Kinase/Extracellular-Signal Regulated Kinase (MAPK/ERK), Protein Kinase C (PKC), and Protein Kinase B (AKT/PKB) pathways. Conversely, the p38 MAPK pathway, which signals for a cell to undergo apoptosis, is activated when cells are placed under stressful conditions such as those experienced after a dose of ionizing radiation. When bFGF is added to Human Umbilical Vein Endothelial Cells (HUVEC), the level of radiation-induced apoptosis is reduced. If inhibitors of these signaling pathways are added, they will block the protective bFGF effect and restore the high levels of radiation-induced apoptosis. However, before these experiments can be performed, the effective dose range of the inhibitors and bFGF in HUVECs must be established. To determine this, we employed a reliable bioassay in a convenient format: cell proliferation measured by XTT cleavage in a 96-well plate. Cells are seeded and changed to low serum medium. The AKT/PKB pathway can be blocked with LY294002 hydrochloride which inhibits the activity of Phosphatidylinositol 3-Kinase (PI3K). The PKC pathway can be inhibited with U73122, which blocks the activation of phospholipase C-gamma (PLC). SB202190 inhibits the alpha and beta isoforms of p38 and induces apoptosis. bFGF is effective in the range of 5-10 ng/mL for this cell type. The IC50 for LY294002, U73122, and SB202190 are 3.3 µM, 1.0 µM and 33.0 µM, respectively. The goal of this study was to optimize the dose of inhibitors that may block the proliferative and protective effects of bFGF in HUVECs. The results of this study are being used in ongoing radiation induced apoptosis assays, where the effects of inhibitors to bFGF radioprotection are being quantified.

Efficacy of sub-chronic low-dose S-Gamma-Vinyl GABA (GVG) in inhibiting methamphetamine-induced increases in [18F]fluoro-deoxyglucose uptake. JESSICA PAI (New York University, New York, NY, 10003) STEPHEN DEWEY (Brookhaven National Laboratory, Upton, NY, 11973)

In previous studies, gamma-vinyl-GABA (GVG, vigabatrin) has been shown to effectively inhibit methamphetamine-induced increases in nucleus accumbens dopamine, demonstrating that GVG could serve as a potential treatment for methamphetamine (METH) addiction. In this study, the effect of sub-chronic low-dose S-GVG was examined to determine if a sub-chronic treatment schedule could successfully reduce [18F]fluoro-deoxyglucose (18FDG) uptake in brain regions where elevated metabolic activity is due to METH administration. Male Sprague-Dawley rats (n=10) received a static scan following a 45 minute awake 18FDG uptake using an R4 microPET imaging (Concorde Microsystems). Animals received a baseline scan (scan 1; mean weight = 136.6 ± 10.8g) and then after two days (scan 2) following an acute METH challenge (1 mg/kg). Over the course of the next 11 days, rats received METH and/or saline (5 pairings) intraperitoneally (I.P.) on alternate days. Animals (206.5 ± 17.9g) were again imaged (scan 3) following a METH challenge. Next, a sub-chronic low-dose GVG (75 mg/kg) schedule was administered I.P. for five consecutive days, then animals (238.6 ± 20.2g) received their final scan (scan 4) following a METH challenge. Results show global increases (18.9 ± 2.7%) in 18FDG uptake in specific brain regions of the brain previously demonstrated to respond to an acute METH challenge. Following the sub-chronic METH administration, increases in 18FDG uptake appeared to be regionally specific, with the greatest increase in the primary motor cortex (5.6%) and decreases occurring in the thalamus (7.9%) and cerebellum (6.4%). Images obtained following the 5-day S-GVG treatment showed global decreases (13.2 ± 4.3%) in 18FDG uptake in specific brain regions. These results indicate that sub-chronic low dose S-GVG effectively inhibits METH-induced increases in 18FDG uptake as seen by the hypometabolism in brain regions activated by METH administration. These findings support the potential use of S-GVG for the treatment of METH addiction.

Functional Somatosensory Activation in Control and Wild Rats. JOEL URENA (State University of New York at Buffalo, Buffalo, NY, 14260) HELENE BENVENISTE (Brookhaven National Laboratory, Upton, NY, 11973)

For the past decade, scientists have studied rodent somatosensory (SS) function and have been able to localize external physical stimuli, such as electrical stimulation, to specific regions of the brain, particularly the SS cortex. One method of measuring SS activation is by using Blood-Oxygen-Level-Dependent (BOLD) functional Magnetic Resonance Imaging (fMRI). Neural activation corresponding to electrical stimulation results in a significant change in blood perfusion levels that can be measured via BOLD fMRI. The aim of this study is to measure and compare SS cortex activation elicited by forepaw and hind paw electrical stimulation between wild and laboratory Norway rats via BOLD fMRI. Because the common wild rat found in the North American region is of the Norway strain, SS activation in laboratory-housed Norway rats will be investigated to allow for comparison. It is hypothesized that SS activation in wild rats will be smaller and sharper because wild rats have to adapt to various environments, avoid predators and search for their own food. The rats were first anesthetized with isoflurane followed by a continuous IV infusion of a-chloralose. Electrodes were inserted in both forepaws and the left hind paw. One paw was stimulated at a time with the following paradigm: 69 seconds of rest, 30 seconds of stimulation, and 90 seconds of rest while MR images were acquired. Data was analyzed using the software STIMULATE. A Student’s t-test was used to construct statistical activation maps. The average increase in BOLD signal corresponding to left forepaw stimulation among six control rats was 4.7%. The average increase in BOLD signal corresponding to right forepaw stimulation among five control rats was 5.6 %. Recent attempts have been made to capture wild rats. However, the attempts were unsuccessful due to the small wild rat population on the Brookhaven National Laboratory campus. Plans will be made to capture wild rats off-campus.

Image Analysis of PET Studies on the Norepinephrine Transporter with (S,S)-[11C]O-methylreboxetine (MRB). JOHN ZABROSKI (St. Joseph's College, Patchogue, NY, 11772) JEAN LOGAN (Brookhaven National Laboratory, Upton, NY, 11973)

The norepinephrine transporter (NET) is responsible for removing norepinephrine from the synaptic cleft. Studies have shown that blocking NETs can help normalize certain pathologies associated with attention deficit hyperactivity disorder, substance abuse and depression by controlling the transmission of neuronal signals. Visualizing the effectiveness of NET inhibitors has been difficult because most known Positron Emission Tomography (PET) radiotracers have high background (non-NET) binding. The radiotracer (S,S)-11C]O-methylreboxetine (MRB) has been identified as a potential NET ligand, and was used to determine if tracer binding predicts regional distribution of NETs in humans by administering the drug atomoxetine, a norepinephrine reuptake inhibitor, to one group. The data from this group and a control group was obtained by a high-resolution positron emission tomograph in three-dimensional mode. The dynamic images were normalized to a standard atlas using Statistical Parametric Mapping (SPM) software. Individual time frames for all the different subjects in each group were combined to form an average dynamic image for each group. Parametric images were formed for each group corresponding to the distribution volume using a one-compartment model. The caudate and putamen were selected as reference regions from the difference images (baseline - atomoxetine). From these images the relative distribution of NETs was determined corresponding to the known distribution of NETs. Results from the parametric image region of interest (ROI) analysis were compared to ROI analysis on individual subjects. Both averaged images and ROI analysis showed that maximum blocking of NETs occurred at 25 mg / kg, with no further effect seen for higher doses. The averaged DVR images allowed for a better visualization of the NET distribution than individual images. The averaged DVR images suggest (S,S)-MRB has greater specificity than other PET ligands for the NET, making it a promising ligand for visualizing the effectiveness of NET inhibitors in humans.

Imaging Nanoparticles in Living Systems. JOSEPH CARRION (The City College of New York, New York, NY, 10034) WYNNE SCHIFFER (Brookhaven National Laboratory, Upton, NY, 11973)

Nanotechnology and Quantum Dots in particular hold much promise for biomedical engineering since, by virtue of their size, nanomaterials can permeate many of the body’s natural barriers. It is not, however, known how these nanometer-sized particles will disperse within living systems, nor has it been established what physiochemical properties such as size, surface modification, and core material will alter this in-vivo dispersion. In this study we use in-vivo imaging to look at the effects of [11C] Cadmium Selenide/Zinc Sulfur (CdSe/ZnS) and [11C] Gold nanoparticles (Au). Ten Swiss-Webster (SW) mice were injected with an intravenous bolus of thiol conjugated [11C] Cadmium Selenide/Zinc Sulfur quantum dots (QDs) at two concentrations, both coated and uncoated with the surfactant Tween 80. Five of these mice were sacrificed immediately, and five were sacrificed after 6 weeks as part of the comprehensive imaging studies. All mice organs harvested were placed in a 4% Formaldehyde/1% glutaraldehyde in phosphate buffer with 5% Sucrose added for Transmission Electron Microscopy visualization. The kidney and liver of the mice were cryosectioned and nanoparticle distribution at a light microscope level was visualized using the fluorescent properties of QDs to estimate accumulation. There appears to be a concentration dependent distribution in the mouse kidney and liver: animals injected with smaller concentration of QDs show less fluorescence at 470nm in kidney compared to animals receiving higher concentrations. High Performance Liquid Chromatography (HPLC, computer automated BAS System) with electrochemical detection was used to estimate concentration of CdSe/ZnS nanoparticles of 2 nanometer and 10 nanometer sizes. These studies used in-vivo imaging together with light microscopy to explore the effect of variations in size and surfactant coating on the dispersion of these particles in living systems. Image-guided localization with Micro-PET allows the modeling of distribution of [11C] CdSe/ZnS nanoparticles of 2nm and 10nm size in a living system.

Parallel changes in behavior and neurochemistry resulting from surgical implantation into the brains of rats. DAVID FRUMBERG (Cornell University, Ithaca, NY, 14853) WYNNE SCHIFFER (Brookhaven National Laboratory, Upton, NY, 11973)

Surgical implants into the brain can cause long-term behavioral and functional deficits in vivo. Using a routine surgical procedure, intracerebral stylets were stereotaxically inserted into the right striatum of anesthetized rats. Novel object recognition (NOR) tests were administered to subjects 3 days prior to and 3, 7, 14, and 56 days after surgery to assess intellectual performance. Metabolic imaging with 18F-fluorodeoxyglucose (18FDG) occurred 28 and 57 days after surgery. Behavioral deficits significantly appear 3 days post-injury, where performance has decreased by 17.3%; performance decreased by 24.3% after 7 days, 38.0% after 14 days, and 41.7% after 56 days. Subjects that did not receive implants devoted a mean of 57.1% of their investigation time with the novel object, while the mean for subjects that received implants was 50.2%. This observation suggests that animals with implants failed to recognize the familiar object as such. Normalized PET analyses demonstrated a significant decrease in glucose uptake after surgery in the entire hemisphere ipsilateral to the implant relative to the contralateral hemisphere. Greatest metabolic deficits occurred in the motor cortex (-16.4%; p=.0005), sensory cortex (-10.3%; p=.009), dorsal striatum (-13.7%; p=.007), and thalamus (-9.2%; p=.006) of the side of implantation compared to the intact side. Metabolic deficits in the motor cortex significantly correlated with a decline in general locomotion observed three days following the surgical implant (R2=0.63). No metabolic recovery was observed over the two-month period. These results imply that the window for treatment of open head injury in humans is much shorter than previously believed.

Qualitative Analysis. CARMELITA ROSALES (Idaho State University, Pocatello, ID, 83209) ROBERT RICHARDS (Idaho National Laboratory, Idaho Falls, ID, 83415)

Qualitative analysis is research that focuses on how individuals and groups view and understand the world. Qualitative research is one of the two major approaches to research methodology in social science and involves investigating opinions, behaviors and experiences from the informants' points of view and constructing meaning out of their experiences. Three methods of gathering qualitative data include: participant observation, interview, and document analysis. The Center for Human Performance Improvement (HPI) administered a baseline survey to three separate organizations within the INL. The purpose of the baseline was to measure the strengths or weaknesses of specific organizational attributes. After researching and studying the qualitative analysis processes, we developed our own methodology for analyzing the survey comments. We conducted a qualitative analysis of the comments that were gathered by these surveys; we received over 5,500 comments from the three organizations. We read through each section, came up with themes that appeared in each area, and then found themes that represented the entire survey, we then wrote a report of our findings. Each organization was given its report and improvement actions are being pursued. As the report for one of the organizations was a strong indication of a problem, we decided to study the safety culture for that organization in an attempt to discover what factors contributed to this organization’s view on current safety programs.

Rehabilitation and Implementation of Scintimammography Gamma Camera Integrated into a Stereotactic Core Biopsy Digital X-ray System. CLARISSA FREEMAN (Hampton University, Hampton, VA, 23606) STAN MAJEWSKI (Thomas Jefferson National Accelerator Facility, Newport News, VA, 23606)

Biopsies are used to accurately confirm the presence of breast cancer when suspicious lesions are found. A biopsy is a small sampling of tissue that can be tested to determine whether there is malignancy. Approximately three out of every four women still have unnecessary biopsies. A scintimmamography gamma camera integrated into a stereotactic core biopsy digital x-ray system may be used to reduce unnecessary biopsies. The scintimmamography gamma camera is a custom-built mini gamma camera with an active area of 5.3 cm by 5.3 cm. It is based upon a 2 by 2 array of position-sensitive photomultiplier tubes made by Hamamatsu. The system obtains dynamic scintimammographic data by performing dynamic radiopharmaceutical uptake studies; these images can confirm or negate the need for a biopsy, leading to fewer unnecessary procedures. The objective of the project was to remove the system out of its clinical setting for repair and calibration. It has a primary detector head for most clinical settings, as well as a second detector to be used as an auxiliary. A new crystal map was created for the system, detector head energies were calibrated, and corrected images were taken. In addition, electrical components were replaced and appropriately labeled. For optimal stability, calibrations were performed using Kmax Sparrows NT development package. A dynamic energy range for detector head one was found to be 540 volts, and the second detector range was found to be 580 volts. The system was tested once all repairs were complete and calibrations were finalized. In the coming months, the system will be put into a clinical environment so that its performance can be tested against traditional detector systems.

The Efficacy of the National Ignitions Facility's Ergonomic Program. NAOMI SHAH (University of California San Diego, La Jolla, CA, 92092) STEVEN MCCONNELL (Lawrence Livermore National Laboratory, Livermore, CA, 94550)

Ergonomic injuries have become an increasing concern for office workers and their employers due to the rise in computer-based work. These injuries, as with all chronic injuries, are most prevalent in the older members of the work force due to a longer exposure to chronic insults to their bodies. In 2005, over half of the recorded illness/injury cases at the National Ignitions Facility (NIF) at Lawrence Livermore National Laboratory (LLNL) were ergonomic cases. In order to reduce the number of such cases and their associated costs, NIF has implemented an ergonomic program in which the goal is to evaluate their 1,200 employees. The current process of creating a list of employees who need an evaluation, making an appointment with the employees, performing the evaluation, and following up afterwards proved to have some problems which inhibit efficiency. To enhance the process of forming a list of employees for evaluations, a new database has been developed and is being tested. This allows the evaluator to receive daily updated lists. In order to easily set up appointments and yield a larger response rate, it was found that a Meeting Maker proposal followed by an Email works the best. The evaluator uses the NIF Comfort Survey to help asses the employee’s work space; this survey proves to be sufficient in identifying the needs of the employee. Overall, the ergonomic program has made a good start in preventing further ergonomic injuries, and with implementation of the new recommendations, will prove to be an efficacious program.

Tolerance of Rat’s Spinal Cord to Dose-Fractionated Irradiation with Arrays of Parallel X-ray Microbeams. SASHEEN FERGUSON (Stony Brook University, Stony Brook, NY, 11794) AVRAHAM DILMANIAN (Brookhaven National Laboratory, Upton, NY, 11973)

It has been shown that single-exposure to arrays of parallel, synchrotron-generated x-ray microbeams is well tolerated by normal tissues in laboratory animals at doses up to several hundred Gy. The tissues studied include the brain and spinal cord of the rats. We examined such a tolerance to dose-fractionated irradiations with microbeam arrays. Rats were irradiated daily for four days with microbeam arrays made of 27-µm beams spaced 200 µm on-center.   The daily in-beam incident dose was 400 Gy. The angles of the irradiations were 45º apart from each other. The animals were monitored by weighing and the behavioral test of "Open Field" to evaluate any potential loss of sensorimotor performance, and the results were compared to those in unirradiated controls. As of 15 days after the last irradiation the rats are gaining weight and performing normally in the Open Field test. They will be kept for one year. Afterwards these animals will be euthanized for histology.

Uncovering the neurobiological underpinnings of aggression. OLGA YELIOSOF (State University of New York at Stony Brook, Stony Brook, NY, 11794) RITA GOLDSTEIN/NELLY KLEIN (Brookhaven National Laboratory, Upton, NY, 11973)

Recently, a polymorphism in Monoamine Oxidase A (MAOA) genotype (high vs. low) was found to modulate inhibitory control of behavior. As an enzyme responsible for the metabolism of catecholamines, MAOA is a relevant target for the study of potential risk for violent behavior that these neurotransmitters modulate. Indeed, functional brain differences were found between the MAOA genotype groups in brain regions associated with inhibitory control in recent studies. Specifically, significant differences in functional brain reactivity to emotional challenges in frontolimbic brain regions were noted between the two groups. Based on these findings, this study examines whether these functional brain differences reflect differential brain MAOA activity and glucose consumption at resting baseline in the anterior cingulate gyrus (ACG) by postulating that the activity of the ACG, which plays a key role in inhibitory control, will differ as a function of MAO-A genotype. Specifically, individuals with low MAOA are expected to have diminished MAO-A levels and baseline metabolism in the ACG, as well as compromised scores on the conflict subscale of the Attention Network Test (ANT), a test of efficiency of conflict resolution. Thirty-eight healthy, non-smoking males were genotyped (high vs. low MAO-A) and their brain MAO-A levels were examined utilizing Positron Emission Tomography (PET) with [11C]clorgyline. Brain glucose metabolism was examined as a baseline brain functioning measure with fluorodeoxyglucose (FDG). ACG was traced on PET images as a region of interest. This neuroimaging data was correlated with the results of the ANT administered as part of a comprehensive neuropsychological battery. Results showed that compared to the high MAO-A group, the low MAO-A group displayed the following: (1) more cognitive conflict on the ANT task (p=0.056) as revealed by an independent sample t-test (2 tailed), (2) marginally increased cognitive conflict correlated with increased metabolism in absolute bilateral ACG (r=0.86 p<0.0001), (3) increased metabolism in bilateral ACG was related to lower relative MAO-A in that region (r=-0.70, p=0.012). These findings suggest possible associations between genetic predisposition, brain functioning, and potential risk for aggressive behavior.