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.

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.

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.

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.

Rapid quality control analysis of (13)C-enriched substrate synthesis by isotope ratio mass spectrometry.

There is a growing interest in the use of (13)C-enriched substrates to investigate metabolic processes in humans. The non-invasive nature of (13)C breath tests makes them attractive to clinicians, particularly because they can be safely used in children. The availability of suitable (13)C-enriched substrates can limit the application of this biotechnology. We have used isotope ratio mass spectrometry to assay the chemical purity and isotopic enrichment of substrates that were synthesised to study gut transit and colonic fermentation. Lactose ureide and lactose [(13)C]ureide were synthesised by acid-catalysed condensation of lactose and urea or (13)C urea, respectively. Glucose ureide and glucose [(13)C]ureide were synthesised by similar methods but required an additional purification step to remove urea of crystallisation. Substrates were analysed by standard analytical techniques and combustion isotope ratio mass spectrometry for carbon and nitrogen content and (13)C-enrichment. Monitoring the C/N ratio proved to be a sensitive assay of chemical purity. Analysis of the percentage composition of C and N (and hence O + H) suggested that lactose ureide crystallises as the dihydrate. It was synthesised with approximately 99% chemical purity and with the theoretical enrichment. Glucose ureide was synthesised with approximately 98% chemical purity but with lower than theoretical enrichment.

(13)C natural abundance in the British diet: implications for (13)C breath tests.

Surprisingly little information is available on the natural abundance of the minor isotope of carbon, (13)C, in common foodstuffs in the British diet. This study therefore aimed to examine the (13)C natural abundance of foodstuffs from a small cross-section of the British diet. The isotopic abundance, delta per mil, was calculated by measurement of the isotope ratio (13)C:(12)C by isotope ratio mass spectrometry. Results from this study were also compared with results from a North American study to highlight the difference in isotopic abundance between Northern European foodstuffs and North American foodstuffs. Such data should prove useful to those planning tracer studies using the stable isotope (13)C where enrichment is measured against a large and variable natural abundance in the body. Minimisation of this basal variation, for example in breath CO(2), can be achieved by controlling dietary intake of foods naturally abundant in (13)C.

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.

Measurement of urinary total 13C and 13C urea by isotope ratio mass spectrometry after administration of lactose [13C]-ureide.

A method of measuring total 13C excreted in urine after oral administration of lactose [13C]-ureide was developed using isotope ratio mass spectrometry. Furthermore, a method to measure 13C urea excreted in the urine was developed. Each urine sample collected over a 24 hour period, after administration of the tracer dose, was analysed for both total 13C and 13C urea. Combustion of the dried urine samples allowed measurement of the total 13C content. Treatment of urine samples with urease (EC 3.5.1.5) and analysis by isotope ratio mass spectrometry of the CO2 evolved allowed measurement of 13C urea in the urine sample. The total 13C and 13C urea content of each urine sample, obtained throughout the protocol, were compared to total 13C and 13C urea contents of a urine sample taken before the test. This allowed calculation of the fraction of tracer incorporated into urea and the fraction of tracer excreted in total. Analyses showed that approximately 15% of the dose administered, in terms of 13C, was recovered in the urine over the sampling period. Further analysis for urinary 13C urea showed that less than 1% of the label was incorporated into urea excreted over the sampling period.

The effect of clonidine on cerebral blood flow velocity, carbon dioxide cerebral vasoreactivity, and response to increased arterial pressure in human volunteers.

BACKGROUND: Because patients may be taking clonidine chronically or may be receiving it as a premedication before surgery, the authors investigated its effect on cerebral hemodynamics. METHODS: In nine volunteers, middle cerebral artery mean blood flow velocity (Vm) was measured using transcranial Doppler ultrasonography (TCD). CO2 vasoreactivity was measured before clonidine administration (preclonidine), 90 min after clonidine, 5 microg/kg orally, then following restoration of mean arterial pressure (MAP) to the preclonidine level. In addition, Vm was measured after a phenylephrine-induced 30-mmHg increase in MAP. RESULTS: After clonidine administration, Vm decreased from 62 +/- 9 to 48 +/- 8 cm/s (P < 0.01), and MAP decreased from 86 +/- 10 to 63 +/- 5 mmHg (P < 0.01; mean +/- SD). Clonidine decreased the CO2 vasoreactivity slope from 2.2 +/- 0.4 to 1.2 +/- 0.5 cm x s(-1) x mmHg(-1) (P < 0.05); restoring MAP to the preclonidine level increased the slope to 1.60 +/- 0.5 cm x s(-1) x mmHg(-1), still less than the preclonidine slope (P < 0.05). CO2 vasoreactivity expressed as a percentage change in Vm, decreased after clonidine, 3.5 +/- 0.8 versus 2.4 +/- 0.8 %/mmHg (P < 0.05); this difference disappeared after restoration of MAP, 3.1 +/- 1.2 %/mmHg. With a 30-mmHg increase in MAP, Vm increased by 13% before and after clonidine (P < 0.05). CONCLUSIONS: Clonidine, 5 microg/kg orally, decreases Vm and slightly attenuates cerebral CO2 vasoreactivity, therefore decreased cerebral blood flow and mildly attenuated CO2 vasoreactivity should be anticipated.

Venous bleeding during transsphenoidal surgery: its association with pre- and intraoperative factors and with cavernous sinus and central venous pressures.

Venous bleeding during transsphenoidal surgery for resection of pituitary tumors is a common problem that interferes with the performance of the surgical procedure. In this study, data were collected prospectively from 50 patients to determine whether there were pre- or intraoperative factors (e.g., patient demographics, type and grade of pituitary tumor, intraoperative hemodynamics) associated with venous bleeding which might be used to predict its occurrence. In addition, central venous pressure (CVP), and cavernous sinus pressure (CSP) were measured in 13 patients to evaluate the relationship of these pressures to each other and to the severity of venous bleeding. During resection of the pituitary tumor, the severity of venous bleeding was graded as minimal, moderate, or severe, the latter two grades requiring therapeutic intervention. Moderate bleeding requiring intervention occurred in 15 of the 50 patients, and resolved in all cases. Moderate bleeding was not related to CSP or CVP, and no specific associated factor was observed. CSP was not correlated with CVP, and was higher than that predicted from the CVP and the position of the patient or the hydrostatic gravitational pressure gradient. These results suggest that it is not possible to predict in advance which patients will have problems with venous bleeding, but that simple therapeutic maneuvers are effective.

Analysis of cloned cDNAs differentially expressed in adapting remnant small intestine after partial resection.

After partial resection, the remnant small intestine undergoes an adaptive response. Little is known about the molecular and cellular basis of intestinal adaptation. To identify genes transcriptionally regulated in response to loss of functional bowel surface area, we have isolated cDNAs differentially expressed in the adaptive ileum 48 h after 70% proximal small intestinal resection. A cDNA library constructed from the remnant ileum of rats subjected to resection was screened using subtractive hybridization techniques. Several groups of cDNA clones that were induced during intestinal adaptation were isolated. The first included liver fatty acid binding protein, apolipoprotein A-IV, cellular retinol binding protein II, and ileal lipid binding protein. These all encode proteins involved in the absorption, metabolism, and trafficking of nutrients. A second group included the catalytic subunit of protein phosphatase 1 delta, a 78-kDa glucose-regulated protein (grp 78; a glucose-regulated member of the 70-kDa heat-shock protein family), and several pancreatitis-associated proteins. A third group of induced genes contained novel cDNAs. To better characterize the adaptive response, the temporal, spatial, and cellular patterns of expression of several of these genes were analyzed with the use of immunohistochemical and in situ hybridization techniques. These studies indicate that during early adaptation, genes involved in nutrient trafficking, protein processing, and cell cycle regulation are transcriptionally regulated in the residual small intestine in distinct temporal and regional patterns consistent with a complex multifaceted response to intestinal resection.

Enterocytic gene expression in intestinal adaptation: evidence for a specific cellular response.

After massive small bowel resection, the remnant gut epithelium undergoes an adaptive response marked by an increase in villus height, crypt depth, and crypt cell production rate. Although morphological features of gut adaptation have been well characterized, the differentiation status and response of epithelial cells populating the adaptive villus is unclear. To address these issues, cell-specific and spatial patterns of expression of a set of enterocytic genes were characterized in rats after 70% small bowel resection. The liver and intestinal (I) fatty acid binding protein (FABP) and apolipoprotein A-I (apo A-I) and apo A-IV genes were studied because they exhibit unique regional and cell-specific patterns of expression in the developing and adult gut. At 48 h after surgery, apo A-IV and I-FABP mRNA levels were increased up to 3.5-fold in adaptive remnant ileum compared with sham-operated or sham-resected control ileum. In situ hybridization and immunohistochemical analyses revealed a marked increase in enterocytic apo A-IV mRNA and protein expression in the adaptive ileum, from villus base to tip but not in crypts. By 1 wk after resection, apo A-IV, but not I-FABP, mRNA levels remained elevated in remnant ileum, although duodenal I-FABP mRNA levels were still increased. In contrast, apo A-I mRNA levels were not significantly induced. These results indicate that the enterocyte can respond acutely to loss of small bowel surface area by increasing expression of several genes. This compensatory enterocytic response is spatially (from duodenum to ileum) and temporally regulated. These results suggest initiation of the adaptive response occurs by way of a complex set of molecular pathways involving villus and crypt cells.

Changes in acetylcholine receptor number in muscle from critically ill patients receiving muscle relaxants: an investigation of the molecular mechanism of prolonged paralysis.

OBJECTIVE: Previous reports have described prolonged paralysis after the administration of muscle relaxants in critically ill patients. The purpose of this study was to examine possible pathophysiologic causes for this paralysis by measuring muscle-type, nicotinic acetylcholine receptor number in necropsy muscle specimens from patients who had received muscle relaxants to facilitate mechanical ventilation before death. DESIGN: Prospective laboratory study of human muscle collected at autopsy. SETTING: Medical and surgical intensive care units (ICUs) at a university hospital and a research laboratory. PATIENTS: Fourteen critically ill patients, with a variety of diagnoses, all of whom required mechanical ventilatory support before their deaths in the ICU and who underwent post mortem examination. Patients were arbitrarily divided into three groups, according to their total vecuronium dose and number of days mechanically ventilated before death. Three patients were in the control group (defined as dying within 72 hrs of initiation of ventilatory support and receiving a total dose of < 5 mg of vecuronium). Six patients were in the low-dose group (defined as requiring ventilatory support for > 3 days before death and receiving a total vecuronium dose of < or = 200 mg). Five patients were in the high-dose group (defined as requiring ventilatory support for > 3 days before death and receiving a total vecuronium dose of > 200 mg). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Nicotinic acetylcholine receptor numbers as measured by specific 125I-alpha-bungarotoxin binding to human rectus abdominis muscle obtained at autopsy were determined. In general, receptor number reflected the clinical requirements for the muscle relaxants of each patient. Patients who had increasing requirements for muscle relaxants before death had increases in receptor number, as compared with control values. CONCLUSIONS: The increase in nicotinic acetylcholine receptor number in muscle from patients with an increasing requirement for muscle relaxants before death suggests that nicotinic acetylcholine receptor up-regulation may underlie the increased requirements for muscle relaxants seen in some patients. Furthermore, these findings suggest that muscle relaxant-induced, denervation-like changes may at least be partially responsible for prolonged muscle paralysis after the long-term administration of muscle relaxants. This study may provide the first information into the molecular mechanisms underlying prolonged paralysis.

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.