Low-Dose High-Resolution TOF-PET Using Ionization-activated Multi-State Low-Z Detector Media.

We propose PET scanners using low atomic number media that undergo a persistent local change of state along the paths of the Compton recoil electrons. Measurement of the individual scattering locations and angles, deposited energies, and recoil electron directions allows using the kinematical constraints of the 2-body Compton scattering process to perform a statistical time-ordering of the scatterings, with a high probability of precisely identifying where the gamma first interacted in the detector. In these cases the Line-of-Response is measured with high resolution, determined by the underlying physics processes and not the detector segmentation. There are multiple such media that act through different mechanisms. As an example in which the change of state is quantum-mechanical through a change in molecular configuration, rather than thermodynamic, as in a bubble chamber, we present simulations of a two-state photoswitchable organic dye, a 'Switchillator', that is activated to a fluorescent-capable state by the ionization of the recoil electrons. The activated state is persistent, and can be optically excited multiple times to image individual activated molecules. Energy resolution is provided by counting the activated molecules. Location along the LOR is implemented by large-area time-of-flight MCP-PMT photodetectors with single photon time resolution in the tens of ps and sub-mm spatial resolution. Simulations indicate a large reduction of dose.

Air-transfer production method for large-area picosecond photodetectors.

We have designed and prototyped the process steps for the batch production of large-area micro-channel-plate photomultipliers (MCP-PMT) using the "air-transfer" assembly process developed with single LAPPDTM modules. Results are presented addressing the challenges of designing a robust package that can transmit large numbers of electrical signals for pad or strip readout from inside the vacuum tube and of hermetically sealing the large-perimeter window-body interface. We have also synthesized a photocathode in a large-area low-aspect-ratio volume and have shown that the micro-channel plates recover their functionality after cathode synthesis. These steps inform a design for a multi-module batch facility employing dual nested low-vacuum and ultra-high-vacuum systems in a small-footprint. The facility design provides full access to multiple MCP-PMT modules prior to hermetic pinch-off for leak-checking and real-time photocathode optimization.

Pump-probe spectrometer for measuring x-ray induced strain.

A hard x-ray pump-probe spectrometer using a multi-crystal Bragg reflector is demonstrated at a third generation synchrotron source. This device derives both broadband pump and monochromatic probe pulses directly from a single intense, broadband x-ray pulse centered at 8.767 keV. We present a proof-of-concept experiment which directly measures x-ray induced crystalline lattice strain.

Femtosecond synchronism of x-rays and visible/infrared light in an x-ray free-electron laser.

A way is proposed to obtain ultrashort pulses of intense infrared/visible light in few-femtosecond synchronism with x-rays from an x-ray free-electron laser (XFEL). It makes use of the recently proposed emittance-slicing technique [Emma et al., Phys. Rev. Lett. 92, 074801 (2004)] to both restrict the duration of self-amplified spontaneous emission (SASE) to a few femtoseconds and to lead to a coherence enhancement of near-infrared transition undulator radiation (CTUR). The x-rays and the near-infrared light originate within the XFEL undulator from the same slice of electrons within a bunch and are therefore perfectly synchronized with each other. An example of realizing the scheme at the Linac Coherent Light Source is presented. A few side issues are explored briefly, such as the magnitude of the velocity term versus the acceleration term in the Lienard-Wiechert fields and the possible use of the CTUR as a diagnostic tool for the SASE process itself.

Effect of clozapine, haloperidol, or M100907 on phencyclidine-activated glutamate efflux in the prefrontal cortex.

BACKGROUND: The increase in glutamate efflux in the prefrontal cortex by the psychotomimetic drugs phencyclidine (PCP) and ketamine may produce the dopaminergic and some of the behavioral effects of these drugs. Here, we examined whether antipsychotic drugs influence this increase. METHODS: The effect of haloperidol, clozapine or the 5-HT(2A) antagonist, M100907, on PCP-induced increase in cortical glutamate efflux was examined by microdialysis. Because previous studies had suggested that M100907 attenuates some behavioral effects of PCP, we also examined the effect of M100907 on PCP-induced cortical and accumbal dopamine activation while making concomitant measures of locomotion and stereotypy. RESULTS: Haloperidol, clozapine or M100907 did not significantly block hyperglutamatergic effects of PCP. M100907 was ineffective in inhibiting the dopaminergic and motoric effects of PCP. CONCLUSIONS: These results contrast previous findings with glutamatergic drugs, such as AMPA antagonists or group II metabotropic glutamate agonists, that blocked glutamatergic and motoric effects of PCP. Thus, the PCP glutamate activation model lacks predictive validity for conventional antipsychotics; however, this model may be useful for design of novel classes of drugs that target those symptoms of schizophrenia that are not generally treated with monoamine-based antipsychotics.

Tactile stimulation activates dopamine release in the lateral septum.

Little is known about the functional properties of the dopamine innervation of the lateral septum. In this study, the feasibility of using microdialysis to assess action-potential mediated release of dopamine in the lateral septum was established. A mild stressor, in the form of handling, significantly increased septal dopamine levels, implicating a role for dopamine in sensory-related processing associated with the septal complex.

Reversal of phencyclidine effects by a group II metabotropic glutamate receptor agonist in rats.

Glutamatergic abnormalities have been associated with several psychiatric disorders, including schizophrenia and addiction. Group II metabotropic glutamate receptors were targeted to normalize glutamatergic disruptions associated with an animal model of schizophrenia, the phencyclidine model. An agonist of this group of receptors, at a dose that was without effects on spontaneous activity and corticolimbic dopamine neurotransmission, attenuated the disruptive effects of phencyclidine on working memory, stereotypy, locomotion, and cortical glutamate efflux. This behavioral reversal occurred in spite of sustained dopamine hyperactivity. Thus, targeting this group of receptors may present a nondopaminergic therapeutic strategy for treatment of psychiatric disorders.

Thermoregulatory responses of febrile monkeys during microwave exposure.

We have examined experimentally the question of increased vulnerability to the thermalizing effects of MW exposure during febrile illness. In a controlled ambient temperature of 26 degrees C, autonomic mechanisms of heat production and heat loss were measured in febrile squirrel monkeys during 30-min exposures to 450 or 2450 MHz CW MW fields at different phases of the fever cycle (induction, plateau, defervescence). We have shown that MW energy absorbed during a febrile episode spares endogenous energy production, but may augment the fever if deposited deep in the body, as is the case during exposure at the resonant frequency. The fever may also be exacerbated if the MW exposure occurs late in the febrile episode, a condition that may put an organism at some risk, especially if the field strength exceeds safety guidelines.

Physiological interaction processes and radio-frequency energy absorption.

Because exposure to microwave fields at the resonant frequency may generate heat deep in the body, hyperthermia may result. This problem has been examined in an animal model to determine both the thresholds for response change and the steady-state thermoregulatory compensation for body heating during exposure at resonant (450 MHz) and supra-resonant (2,450 MHz) frequencies. Adult male squirrel monkeys, held in the far field of an antenna within an anechoic chamber, were exposed (10 min or 90 min) to either 450-MHz or 2,450-MHz CW fields (E polarization) in cool environments. Whole-body SARs ranged from 0-6 W/kg (450 MHz) and 0-9 W/kg (2,450 MHz). Colonic and several skin temperatures, metabolic heat production, and evaporative heat loss were monitored continuously. During brief RF exposures in the cold, the reduction of metabolic heat production was directly proportional to the SAR, but 2,450-MHz energy was a more efficient stimulus than was the resonant frequency. In the steady state, a regulated increase in deep body temperature accompanied exposure at resonance, not unlike that which occurs during exercise. Detailed analyses of the data indicate that temperature changes in the skin are the primary source of the neural signal for a change in physiological interaction processes during RF exposure in the cold.

Down syndrome complicated by hemoglobin S/beta+ thalassemia. Atypical expression of coexistent disease.

The chance occurrence of Down syndrome and sickle cell disease is an extremely rare event. The patient presented in this article is the only reported case, based on medical literature review, of Down syndrome coexisting with sickle cell disease due to hemoglobin S/beta+ thalassemia. He had multiple recurrent aplastic crises and severe psychomotor and growth retardation. The physiologic basis for the atypical manifestations of both of his disorders is the subject of this report.

Use of plasmid profiles to detect changes in strains of Staphylococcus aureus during poultry processing.

The plasmid profiles of Staphylococcus aureus strains isolated at different stages in three poultry processing plants have been examined. Changes in profiles were seen in two plants after the plucking stage and the appearance of these new profiles correlated with the presence of an endemic strain, as suggested previously by increases in bacterial counts and changes in biotypes at the same stage. A third plant in which such changes did not occur showed no change in profiles. Plasmid profiles are therefore a rapid and sensitive method for distinguishing endemic strains within a plant from the flora of the incoming birds. Certain profiles also appeared to correspond with particular biotypes and certain phage types.

Thermoregulatory adjustments in squirrel monkeys exposed to microwaves at high power densities.

The present study was undertaken to investigate the thermal adjustments of squirrel monkeys exposed in a cold environment to relatively high energy levels of microwave fields. The animals (Saimiri sciureus) were equilibrated for 90 min to a cool environment (Ta = 20 degrees C) to elevate metabolic heat production (M). They were then exposed for brief (10-min) or long (30-min) periods to 2,450-MHz continuous-wave microwaves. Power densities (MPD) were 10, 14, 19, and 25 mW/cm2 during brief exposures and 30, 35, 40, and 45 mW/cm2 during long exposures (rate of energy absorption: SAR = 0.15 [W/kg]/[mW/cm2]). Individual exposures were separated by enough time to allow physiological variables to return to baseline levels. The results confirm that each microwave exposure induced a rapid decrease in M. In a 20 degree C environment, the power density of a 10-min exposure required to lower M to approximate the resting level was 35 mW/cm2 (SAR = 5.3 W/kg). During the long exposures, 20 min was needed to decrease M to its lowest level. Cessation of irradiation was associated with persistence of low levels of M for periods that depended on the power density of the preceding microwave exposure. Vasodilation, as indexed by changes in local skin temperature, occurred at a high rate of energy absorption (SAR = 4.5 W/kg) and was sufficient to prevent a dramatic increase in storage of thermal energy by the body; vasoconstriction was reinstated after termination of irradiation. Patterns of thermophysiological responses confirm the influence both of peripheral and of internal inputs to thermoregulation in squirrel monkeys exposed to microwaves in a cool environment.

Thermoregulatory consequences of long-term microwave exposure at controlled ambient temperatures.

This study was designed to identify and measure changes in thermoregulatory responses, both behavioral and physiological, that may occur when squirrel monkeys are exposed to 2450-MHz continuous wave microwaves 40 hr/week for 15 weeks. Power densities of 1 or 5 mW/cm2 (specific absorption rate = 0.16 W/kg per mW/cm2) were presented at controlled environmental temperatures of 25, 30, or 35 degrees C. Standardized tests, conducted periodically, before, during, and after treatment, assessed changes in thermoregulatory responses. Dependent variables that were measured included body mass, certain blood properties, metabolic heat production, sweating, skin temperatures, deep body temperature, and behavioral responses by which the monkeys selected a preferred environmental temperature. Results showed no reliable alteration of metabolic rate, internal body temperature, blood indices, or thermoregulatory behavior by microwave exposure, although the ambient temperature prevailing during chronic exposure could exert an effect. An increase in sweating rate occurred in the 35 degrees C environment, but sweating was not reliably enhanced by microwave exposure. Skin temperature, reflecting vasomotor state, was reliably influenced by both ambient temperature and microwaves. The most robust consequence of microwave exposure was a reduction in body mass, which appeared to be a function of microwave power density.

Minimal changes in hypothalamic temperature accompany microwave-induced alteration of thermoregulatory behavior.

This study probed the mechanisms underlying microwave-induced alterations of thermoregulatory behavior. Adult male squirrel monkeys (Saimiri sciureus), trained to regulate the temperature of their immediate environment (Ta) behaviorally, were chronically implanted with Teflon reentrant tubes in the medical preoptic/anterior hypothalamic area (PO/AH), the brainstem region considered to control normal thermoregulatory processes. A Vitek temperature probe inserted into the tube measured PO/AH temperature continuously while changes in thermoregulatory behavior were induced by either brief (10-min) or prolonged (2.5-h) unilateral exposures to planewave 2,450-MHz continuous wave (CW) microwaves (E polarization). Power densities explored ranged from 4 to 20 mW/cm2 (rate of energy absorption [SAR] = 0.05 [W/kg]/cm2]). Rectal temperature and four representative skin temperatures were also monitored, as was the Ta selected by the animal. When the power density was high enough to induce a monkey to select a cooler Ta (8 mW/cm2 and above), PO/AH temperature rose approximately 0.3 degrees C but seldom more. Lower power densities usually produced smaller increases in PO/AH temperature and no reliable change in thermoregulatory behavior. Rectal temperature remained constant while PO/AH temperature rose only 0.2-0.3 degrees C during 2.5-h exposures at 20 mW/cm2 because the Ta selected was 2-3 degrees C cooler than normally preferred. Sometimes PO/AH temperature increments greater than 0.3 degrees C were recorded, but they always accompanied inadequate thermoregulatory behavior. Thus, a PO/AH temperature rise of 0.2-0.3 degrees C, accompanying microwave exposure, appears to be necessary and sufficient to alter thermoregulatory behavior, which ensures in turn that no greater temperature excursions occur in this hypothalamic thermoregulatory center.

Incidence and properties of Staphylococcus aureus associated with turkeys during processing and further-processing operations.

The incidence of Staphylococcus aureus on turkeys sampled at various stages of processing and further-processing was determined on four occasions at each of three different processing plants. For freshly-slaughtered birds, counts from neck skin varied from plant to plant over the range less than 10(2) to greater than 10(5)/g but in all cases the corresponding counts obtained from carcasses sampled after chilling rarely exceeded 10(3)/g and the same was true for samples of mechanically recovered meat (MRM), the final raw product examined. Despite the limited susceptibility of isolates from the different factories to typing by means of either standard human or poultry bacteriophages (55-94% untypable), evidence was obtained with the aid of biotyping for the presence of both human and animal-derived strains. However, some biotypes isolated from MRM were not detected at earlier stages of processing. At one processing plant, an "indigenous' type of S. aureus was clearly demonstrated. It occurred in high numbers in the defeathering machines (up to 10(5)/swab), was found on carcasses at all subsequent stages of processing over the survey period and was shown to survive routine cleaning and disinfection procedures. Isolates of this type produced unusually large amounts of extracellular "slime' in artificial culture. Two of the three processing plants yielded isolates which were enterotoxigenic. Of 55 strains from Plant 1, 60% produced enterotoxin C and all were of the "indigenous' type. In the case of Plant 2, only two type D- and one type F-producing strain were found.

Behavioral thermoregulation in the squirrel monkey: adaptation processes during prolonged microwave exposure.

During 10-min exposures to 2450-MHz microwaves at a power density of 6-8 m W/cm2, squirrel monkeys reliably select a cooler environment. Exposure duration, at power densities above and below this threshold, was the parameter investigated in these experiments. Monkeys were restrained in the far field of a horn antenna inside a 1.8 x 1.8 x 2.5 m anechoic chamber which was heated and cooled by forced convection. The animals learned to control the temperature of the circulating chamber air by selecting between cold (10-15 degrees C) and warm (50-55 degrees C) air sources. During the experiments, they were exposed to 12.4-cm (2450-MHz) continuous-wave microwaves for periods from 5 to 150 min. Microwave power densities explored were 4, 10, and 20 mW/cm2 which represent rates of whole-body energy absorption that range from approximately, .6 to 3.0 W/kg. No microwaves were present during 4-hr control experiments. The 4 mW/cm2 microwave exposure did not modify thermoregulatory behavior, no matter how long it lasted. The 10 and 20 mW/cm2 exposures stimulated the monkeys to select ambient temperatures 1.5 and 3.0 degrees C cooler than control levels, respectively. Except during the first microwave presentation of a series, or during the early minutes of a single long exposure, duration had no significant effect on selection of air temperature or on the body temperatures achieved thereby.

Adjustments in metabolic heat production by squirrel monkeys exposed to microwaves.

Squirrel monkeys (Saimiri sciureus) were exposed in the far field of a horn antenna to both brief (10-min) and prolonged (90-min) periods of 2,450-MHz continuous microwaves. Ambient temperature (Ta) was constant at 15, 20, or 25 degrees C. Microwave power density ranged from 2.5 to 10 mW/cm2, representing a range of whole-body energy absorption from 0.4 to 1.5 W/kg. Reliable reductions in metabolic heat production (M), calculated from oxygen deficit in the monkey's expired air, were initiated at all Ta by 10-min whole-body exposures to power densities of 4 mW/cm2 (2 monkeys) or 6 mW/cm2 (1 monkey) and above. The magnitude of M reduction was linearly related to microwave intensity above the threshold level. Termination of microwaves was followed by a rapid M rebound. The change in M produced by a given power density was nearly the same in Ta = 15 and 20 degrees C. During 90-min exposures at Ta = 20 degrees C, the vigorous M reduction to microwave onset adapted slowly, ensuring continual precise regulation of internal body temperature. Thus cold-exposed endotherms readily compensate for microwave-induced body heating by reducing endogenous heat production.

Microwaves induce peripheral vasodilation squirrel monkeys.

Vasomotor activity in cutaneous tail veins was indexed by changes in local skin temperature during exposure of the whole body to 12.3-centimeter continuous microwaves. At an ambient temperature (26 degrees C) just below that at which tail vessels normally vasodilate, criterion dilation was initiated by 5-minute exposures to a microwave power density of 8 milliwatts per square centimeter. This intensity deposits energy equivalent to approximately 20 percent of the monkey's resting metabolic rate but produces no observable change in deep body temperature. Intensity increments of 3 to 4 milliwatts per square centimeter for 1 degree C reductions in ambient temperature below 26 degrees C produced identical responses. That no vasodilation occurred during infrared exposures of equivalent power density suggests that noncutaneous thermosensitive structures may mediate microwave activation of thermoregulatory responses in the peripheral vasomotor system.

Comparison of media and methods for counting Clostridium perfringens in poultry meat and further-processed products.

A Most Probable Number (MPN) method involving Differential Reinforced Clostridial Medium followed by streaking on Willis & Hobbs medium was compared with direct plating of samples on Tryptose-Sulphite-Cycloserine agar without egg yolk, and two forms of Oleandomycin-Polymyxin-Sulphadiazine-Perfringens agar, one being prepared from a commercial, dehydrated product. With skin samples taken from chicken carcasses at different stages of processing, the three direct plating media gave similar counts of Cl. perfringens whereas results obtained with the MPN method were consistently lower. Although counts of Cl. perfringens from various further processed products were usually less than 10/g, the three plating media showed similar specificity for this organism. All media supported good growth of reference strains of Clostridium perfringens but it was found that physiologically similar species, including Cl. absonum, Cl. paraperfringens and Cl. perenne also grew uninhibited in these media and produced colonies identical with those of Cl. perfringens, thus indicating the need for confirmatory tests for Cl. perfringens when examining natural samples.