First Observation of Cyclotron Radiation from MeV-Scale e

We present an apparatus for detection of cyclotron radiation yielding a frequency-based ß^{±} kinetic energy determination in the 5 keV to 2.1 MeV range, characteristic of nuclear ß decays. The cyclotron frequency of the radiating ß particles in a magnetic field is used to determine the ß energy precisely. Our work establishes the foundation to apply the cyclotron radiation emission spectroscopy (CRES) technique, developed by the Project 8 Collaboration, far beyond the 18-keV tritium endpoint region. We report initial measurements of ß^{-}'s from ^{6}He and ß^{+}'s from ^{19}Ne decays to demonstrate the broadband response of our detection system and assess potential systematic uncertainties for ß spectroscopy over the full (MeV) energy range. To our knowledge, this is the first direct observation of cyclotron radiation from individual highly relativistic ß's in a waveguide. This work establishes the application of CRES to a variety of nuclei, opening its reach to searches for new physics beyond the TeV scale via precision ß-decay measurements.

Pediatric trauma mortality: an ecological analysis evaluating correlation between injury-related mortality and geographic access to trauma care in the United States in 2010.

BACKGROUND: Trauma is the leading cause of mortality in the pediatric population >1 year. Analyzing relationships between pediatric trauma-related mortality and geographic access to trauma centers (among other social covariates) elucidates the importance of cost and care effective regionalization of designated trauma facilities. METHODS: Pediatric crude injury mortality in 49 United States served as a dependent variable and state population within 45 minutes of trauma centers acted as the independent variable in four linear regression models. Multivariate analyses were performed using previously identified demographics as covariates. RESULTS: There is a favorable inverse relation between pediatric access to trauma centers and pediatric trauma-related mortality. Though research shows care is best at pediatric trauma centers, access to Adult Level 1 or 2 trauma centers held the most predictive power over mortality. A 4-year college degree attainment proved to be the most influential covariate, with predictive powers greater than the proximity variable. CONCLUSIONS: Increased access to adult or pediatric trauma facilities yields improved outcomes in pediatric trauma mortality. Implementation of qualified, designated trauma centers, with respect to regionalization, has the potential to further lower pediatric mortality. Additionally, the percentage of state populations holding 4-year degrees is a stronger predictor of mortality than proximity and warrants further investigation.

Adult and elderly population access to trauma centers: an ecological analysis evaluating the relationship between injury-related mortality and geographic proximity in the United States in 2010.

Background: Ongoing development and expansion of trauma centers in the United States necessitates empirical analysis of the effect of investment in such resources on population-level health outcomes. Methods: Multiple linear regressions were performed to predict state-level trauma-related mortality among adults and the elderly across 50 US states in 2010. The number of trauma centers per capita in each state and the percentage of each state's population living within 45-min of a trauma center served as the key independent variables and injury-related mortality served as the dependent variable. All analyses were stratified by age (adult versus elderly; elderly ≥ 65 years old) and were performed in SPSS. Results: The proportion of a population with geographic proximity to a trauma center demonstrates a consistent inverse linear relationship to injury-related mortality. The relationship reliably retains its significance in models including demographic covariates. Interestingly, access to Levels I and II trauma centers demonstrates a stronger correlation with mortality than was observed with Level III centers. Conclusion: Trauma center access is associated with reduced trauma-related mortality among both adults and the elderly as measured by state reported mortality rates. Ongoing efforts to designate and verify new trauma centers, particularly in poorly-served 'trauma deserts', could lead to lower mortality for large populations.

Comparison of 3 agar media in Fung double tubes and Petri plates to detect and enumerate Clostridium spp. in broiler chicken intestines.

Clostridium perfringens is an anaerobic, spore-forming bacterium that may lead to necrotic enteritis, resulting in poor feed efficiency and increased mortality in chickens. It is estimated that C. perfringens infects almost 1 million people in the United States every year. The objective of this research was to compare the Fung double tube (FDT) and conventional Petri plates using 3 different media to detect and enumerate Clostridium spp. in chicken intestines. Nine Cobb 500 broilers were randomly selected and euthanized at 21 and 42 d of age for a total of 18 samples. The jejunum and ileum from each broiler were harvested and studied in 2 methods and 3 media combinations, utilizing a 2 × 3 factorial totaling 6 treatments. The 2 methods were FDT and conventional Petri plates, and the 3 media were Shahidi-Ferguson Perfringens (SFP) with egg yolk supplement, polymyxin B, and kanamycin (E); SFP with polymyxin B and kanamycin (P); and SFP with d-cycloserine (C). Enumerations were performed after 24 h of incubation at 37°C. At 21 d, counts using medium C with FDT (4.51 log10 cfu/g) and plates (2.38 log10 cfu/g) were higher (P < 0.05) than using media E or P. On d 42, there were no differences among plate treatments and medium E had the highest counts (0.98 log10 cfu/g). Of all the FDT, medium C (5.35 log10 cfu/g) had the highest counts (P < 0.05), followed by medium P (3.54 log10 cfu/g). This study illustrates that the FDT method is able to enumerate Clostridium spp. at higher levels (P < 0.001) than the conventional Petri plate method; therefore, the FDT should be implemented and further explored.

Monitoring infection with Epstein-Barr virus among seromismatch adult renal transplant recipients.

Patients who undergo Epstein-Barr virus (EBV) seromismatch (D+/R-) transplants have a higher risk for the development of post-transplant lymphoproliferative disorder (PTLD). Adult renal transplant recipients at a single institution were prospectively monitored for EBV during the first year post-transplant. Over a 2-year period, 34 patients (7.78%) were identified as being EBV D+/R-recipients. Patients who developed symptoms or had persistent viremia were pre-emptively administered rituximab. Six recipients were discharged without monitoring on the protocol. Of those six, three (50%) developed PTLD and all three lost their grafts. Twenty (60.6%) of the 34 recipients developed viremia during the first year post-transplant. Of the recipients who became viremic, six (30%) received rituximab. None of the six who received rituximab-developed PTLD. We found that recipients who were not monitored on the protocol were more likely to have PTLD and graft loss compared to those who were (p = 0.008). Post-transplant monitoring of adults who undergo EBV D+/R-kidney transplants for viremia and symptoms associated with EBV infection may prompt intervention which reduces the incidence of PTLD within the first year. Use of rituximab in preventing PTLD among patients with primary EBV infection requires further prospective study to determine its overall safety and efficacy.

Effects of dry aging of bone-in and boneless strip loins using two aging processes for two aging times.

This experiment investigated the combined effects of two dry-aging methods (unpackaged and in a bag), two loin-cut styles (bone-in shell loins and boneless strip loins), and two aging times (21 and 28days) on the physical, chemical, sensory, and microbial properties of dry-aged beef. Sections from shell and strip loin were assigned randomly to be aged unpackaged or aged packaged in a bag with high moisture permeability. Weight losses increased with aging time. Shell loins lost more (P<0.05) weight during aging compared with strip loins; dry aging in a bag had less (P<0.05) weight loss than unpackaged aging. There were no differences (P>0.05) in any of the sensory traits between shell and strip loins or dry aging using a traditional method or in a bag. Dry aging in a bag creates positive effects on yields, no negative effects on product quality, and adds flexibility and control of the aging environment.

Relative potencies for barbiturate binding to the Torpedo acetylcholine receptor.

1. The structural requirements of an allosteric barbiturate binding site on acetylcholine receptor-rich membranes isolated from Torpedo electroplaques have been characterized by the ability of fourteen barbiturates to displace [14C]-amobarbitone binding. 2. The barbiturates could be grouped into two classes with ten barbiturates producing a strong inhibition of [14C]-amobarbitone binding (class one) and with four exerting minimal effects (class two). 3. Eight of the ten class one barbiturates displaced essentially all of the [14C]-amobarbitone from its binding site, while, at their respective aqueous solubility limits, two of these barbiturates (thiopentone and dimethylbutylbarbitone (DMBB) inhibited [14C]-amobarbitone binding by nearly 80%. The apparent inhibition constants (KI) for the class one barbiturates ranged from 13 microM for amobarbitone to 2.8 mM for barbitone with the other eight agents lying in the range 100-600 microM, and having the rank order pentobarbitone approximately secobarbitone greater than thiopentone greater than DMBB greater than butabarbitone approximately phenobarbitone greater than aprobarbitone greater than allylbarbitone. 4. By contrast, the class two barbiturates had minimal effects even at close to saturating concentrations. [14C]-amobarbitone binding was reduced slightly (less than 30%) by hexobarbitone, mephobarbitone and methohexitone and was enhanced slightly (less than 20%) by metharbitone. 5. All of the class two, but none of the class one barbiturates, were N-methylated.

Identification of motor pathways during tumor surgery facilitated by multichannel electromyographic recording.

OBJECT: The goal of this study was to determine the usefulness of electromyographic (EMG) recording in locating motor pathways near the central sulcus or internal capsule during surgery. METHODS: Multichannel EMG recordings were compared with visual observation of contralateral body movement that was elicited by direct cortical or subcortical stimulation used to identify motor pathways before and during tumor resection. The EMG recordings were more sensitive than visual observation alone in identifying motor responses: in 30% of cases, responses were identified by EMG recording alone at some point during the operation and, in 9% of cases, EMG responses were the only responses observed. Additionally, EMG recordings often detected seizure activity resulting from electrical stimulation of the cortex that could not be appreciated on visual inspection. No new motor deficits were seen postoperatively in 88% of the patients in this series. CONCLUSIONS: Using EMG recording in addition to motor pathway mapping results in greater sensitivity, allowing the use of lower stimulation levels and facilitating detection of stimulation-induced seizure activity.

Gastrointestinal handling of glycosyl [13C]ureides.

OBJECTIVES: Lactose [(13)C]ureide has been proposed as a noninvasive marker for oro-caecal transit time in adults and children. The present study investigates the handling of lactose [(13)C]ureide ((13)C LU) and glucose [(13)C]ureide ((13)C GU) by the gastrointestinal tract and describes the metabolic fates of these substrates and describes the extent of tracer excretion by different routes. STUDY DESIGN AND SUBJECTS: Four subjects underwent five studies in which they ingested a test meal plus (1) no substrate, (2) (13)C LU, (3) (13)C GU, (4) (13)C LU after predosing with unlabelled lactose ureide and (5) (13)C LU after predosing with glucose ureide. Subjects were studied at home with at least 1 week between tests and they all completed the study. Breath was analysed for (13)CO(2) recovery and urine was analysed for total (13)C recovery, (13)C urea recovery and (13)C GU recovery. RESULTS: The profiles and extent of tracer recovery in breath and urine were similar when either (13)C GU or (13)C LU was used, suggesting similar handling of these substrates by the gut. (13)C GU was the major (13)C-enriched species recovered in the urine even when (13)C LU was consumed. Predosing with either lactose ureide or glucose ureide increased the rate of appearance of tracer, but did not alter transit times. CONCLUSIONS: (13)C LU is hydrolysed to (13)C GU in the small intestine with the fraction of (13)C GU appearing in the urine probably limited by small intestinal permeability. Either (13)C LU or (13)C GU can be used to measure oro-caecal transit time.

Interaction of Bacillus species and Salmonella enterica serovar Typhimurium in immune or inflammatory signaling from swine intestinal epithelial cells.

Previous research evaluated a laboratory strain of Bacillus licheniformis (BL) in a model swine epithelium and found it exerted antiinflammatory effects on Salmonella enterica serovar Typhimurium (Sal)-induced secretion of IL-8. The current investigation evaluated the antiinflammatory actions of Bacillus bacteria available commercially as feed additives for the swine industry. Three isolates were obtained from the product, 2 Bacillus subtilis (BS1 and BS3) and 1 BL (BL2). Swine jejunal epithelial IPEC-J2 cells were seeded into wells on permeable membrane supports and allowed to form confluent monolayers. Treatments included apical pretreatment with BL, BS1, BL2, or BS3 for 17 h without Sal, and the same Bacillus treatments but with 10(8) cfu of Sal added in the final hour of Bacillus incubation. Two additional treatments included negative control wells receiving no bacteria (control) and positive control wells receiving only Sal (10 total treatments). After bacterial incubation, wells were washed and fresh medium containing gentamicin was added. Cells were incubated for an additional 5 h, after which apical and basolateral media were recovered for determination of IL-8 and bacitracin. In addition, inserts with epithelial cells that had received Sal were lysed and lysates were cultured to determine treatment effects on Sal invasion. Exposure to Sal alone provoked an increase in IL-8 secretion from IPEC-J2 cells compared with control wells (P < 0.001 for both the apical and basolateral directions). Pretreatment with each Bacillus isolate followed by challenge with Sal reduced Sal-induced IL-8 secretion in both the apical and basolateral compartments compared with wells receiving only Sal (P < 0.001; except for BS3 apical, P < 0.01). The residual presence of bacitracin could be detected only in BL2 and BL2+Sal. Fewer Sal colonies could be cultured from lysates of BL2+Sal than from the Sal, BS1+Sal, and BS3+Sal treatments (P < 0.001). Results indicate that B. subtilis and BL have the ability to intervene in secretion of the neutrophil chemoattractant IL-8 from swine intestinal epithelial cells. This effect on chemokine secretion by gastrointestinal epithelial cells in vitro could not be explained solely by reduced invasion of epithelial cells by Sal.

Molecular mechanisms of action of general anesthetics.

While a plethora of information exists describing particular changes caused by anesthetics on the molecular architecture of membranes, it is clear that models for anesthetic action remain unproven by rigid scientific criteria. This article describes historical and contemporary theories of how anesthetics act on a molecular level, and examines the discrepancies between these hypotheses and current data.

Evidence for a dual mechanism in the anesthetic action of an opioid peptide.

Loss of righting reflex (LRR) produced by various concentrations of the leucine-enkephalin analog BW831c (TYR.D-ALA.GLY.PHE.D-LEU.NHEt.HCI) was determined in amphibia at 1 atm and 120 atm of helium. EC50 for LRR was 22.1 +/- 1.6 microM and 44 +/- 6.9 microM, respectively. The octanol/water partition coefficient (P) was 26 +/- 3.6, suggesting that this peptide is sufficiently lipid soluble for a classic Meyer-Overton type of anesthetic action. The ratio (EC50 at 120 atm)/(EC50 at 1 atm) for the peptide (2.0 +/- 0.31) was essentially the same as that for the long-chain alcohol, octanol (1.8 +/- 0.08), and similar to those reported for phenobarbital and the gaseous anesthetics. Thus, peptide-induced LRR was reversible by pressure. Peptide-induced LRR also was completely reversible by naloxone, whereas octanol-induced LRR was unaffected by up to 100 microM naloxone. These findings are consistent with a dual mechanism of anesthetic action for this peptide: one, an opiate receptor-specific mechanism, reversible with the specific opiate antagonist, naloxone; the other, a nonspecific mechanism, related to lipid solubility and reversible with the application of the physical agent, pressure.

Inhibition of the nicotinic acetylcholine receptor by barbiturates and by procaine: do they act at different sites?

1. The effects of three barbiturates and the local anesthetic procaine on the ion channel function of mouse nicotinic acetylcholine receptor (nAChR) muscle subtype expressed in Xenopus laevis oocytes were examined by whole-cell voltage-clamp technique. 2. A concentration-response curve for the specific nicotinic agonist dimethylphenylpiperazinium iodide (DMPP) was first determined. This agonist produced increasing whole-cell currents up to a concentration of 100 microM (EC50 = 13 microM), then decreased responses at higher concentrations. 3. The barbiturates (amobarbital, secobarbital, pentobarbital) and procaine produced reversible inhibition of DMPP-induced currents at clinically used concentrations. The two classes of drugs differed in the voltage dependence of the inhibition: procaine-induced inhibition was increased at more negative transmembrane holding potentials (-90 vs. -45 mV); whereas amobarbital-induced inhibition did not vary at different transmembrane potentials. 4. Mutant forms of the nAChR, containing single amino acid changes in the M2 regions of alpha and beta subunits, showed increased sensitivity to procaine but no change in sensitivity to amobarbital-induced inhibition. 5. These electrophysiologic studies provide further evidence that barbiturates and local anesthetics produce inhibition of the nAChR at different sites.

Barbiturates bind to an allosteric regulatory site on nicotinic acetylcholine receptor-rich membranes.

The ability of barbiturates to bind to acetylcholine receptor-rich membranes purified from the electroplaques of Torpedo nobiliana was examined by centrifugation assay. [14C]Amobarbital both partitioned into the membrane and bound displaceably to a site with an equilibrium dissociation constant of 12 microM. This low affinity made the stoichiometry difficult to obtain despite the high specific activity of acetylcholine receptors in this membrane preparation. However, the data are not inconsistent with a stoichiometry of one barbiturate-binding site per acetylcholine-binding site. Displaceable [14C]amobarbital binding was completely inhibited by barbiturates (IC50: amobarbital, 28 microM; secobarbital, 110 microM; pentobarbital, 400 microM; phenobarbital, 690 microM; butabarbital, 690 microM; and barbital, 5.1 mM. alpha-Bungarotoxin had no effect, but cholinergic ligands that convert the acetylcholine receptor to the desensitized state (acetylcholine, carbamylcholine, and, to a lesser extent, d-tubocurarine) partially inhibited displaceable [14C]amobarbital binding. This cholinergic inhibition was prevented by preincubation with alpha-bungarotoxin, implying an allosteric mediation through the classical cholinergic site. This negative interaction between the cholinergic and the barbiturate sites was mutual with barbiturates partially decreasing equilibrium [3H]acetylcholine binding in a saturable fashion with relative affinities that parallel those for inhibiting [14C]amobarbital binding (IC50). These data establish a mutual negative heterotropic interaction between barbiturate-binding sites and cholinergic binding sites on the nicotinic acetylcholine receptor from Torpedo.

The interactions between pressure and anaesthetics.

Compression of animals causes excitation, which has recently posed a barrier to deeper diving. The broad question addressed here is how far the inert gas breathed modifies the excitatory effects of hydrostatic pressure. By using aquatic animals we first show that helium postpones the onset of pressure-induced paralysis by some 35 atm. Next we show that in mammals compressed with helium, five anaesthetic gases (nitrogen, argon, nitrous oxide, carbon tetrafluoride, sulphur hexafluoride) all elevated dose-dependently the median pressure of four distinct phases of the high pressure neurological syndrome (h.p.n.s.) (complete spasms, clonic convulsions, tonic convulsions and non-tonic death). All the gases were equally efficacious relative to their anaesthetic potency. However, the sensitivity of each phase of the h.p.n.s. to anaesthetic gases differed. Most notably, the median pressure for tonic convulsions was elevated about three times more by a given partial pressure of anaesthetic gas than were the median pressures for complete spasms or non-tonic death. These observations can be fitted remarkably well by the hypothesis that a given phase of the h.p.n.s. is activated when some hydrophobic region is compressed beyond a certain critical amount by the application of pressure. Absorption of an inert gas in this region will cause it to expand, tending to elevate the median pressure for that phase of the h.p.n.s. Our data and analysis allow the following conclusions relevant to diving practice. All gases protect against the h.p.n.s. but some phases of this complex syndrome are more effectively controlled than others. Although addition of a second inert gas to helium allows substantial increases in the pressure at which h.p.n.s. occurs, the onset of anaesthesia (or inert gas narcosis) will limit the ultimate gain. The composition of therapeutic gas mixtures becomes more narrowly defined as the pressure increases. The optimum mixture may be different for each phase of the h.p.n.s., and the order of presentation of the h.p.n.s. symptoms may be changed by the second inert gas. We may also predict that physiological sites may exist where helium acts like an anaesthetic. If such sites resulted in physiological dysfunction, addition of a second gas would exacerbate the situation.