Emittance growth in linear induction accelerators

The Dual-Axis Radiographic Hydrotest (DARHT) facility uses bremsstrahlung radiation source spots produced by the focused electron beams from two linear induction accelerators (LIAs) to radiograph large hydrodynamic experiments driven by high explosives. Radiographic resolution is determined by the size of the source spot, and beam emittance is the ultimate limitation to spot size. On the DARHT Axis-II LIA we measure an emittance higher than predicted by theoretical simulations, and even though this axis produces sub-millimeter source spots, we are exploring ways to improve the emittance. Some of the possible causes for the discrepancy have been investigated using particle-in-cell (PIC) codes, although most of these are discounted based on beam measurements. The most likely source of emittance growth is a mismatch of the beam to the magnetic transport, which can cause beam halo.Comment: 20th Int. Conf. on High-Power Particle Beams, Washington, DC, May, 201

Occurrence of invasive pneumococcal disease and number of excess cases due to influenza

Abstract Background Influenza is characterized by seasonal outbreaks, often with a high rate of morbidity and mortality. It is also known to be a cause of significant amount secondary bacterial infections. Streptococcus pneumoniae is the main pathogen causing secondary bacterial pneumonia after influenza and subsequently, influenza could participate in acquiring Invasive Pneumococcal Disease (IPD). Methods In this study, we aim to investigate the relation between influenza and IPD by estimating the yearly excess of IPD cases due to influenza. For this purpose, we use influenza periods as an indicator for influenza activity as a risk factor in subsequent analysis. The statistical modeling has been made in two modes. First, we constructed two negative binomial regression models. For each model, we estimated the contribution of influenza in the models, and calculated number of excess number of IPD cases. Also, for each model, we investigated several lag time periods between influenza and IPD. Secondly, we constructed an "influenza free" baseline, and calculated differences in IPD data (observed cases) and baseline (expected cases), in order to estimate a yearly additional number of IPD cases due to influenza. Both modes were calculated using zero to four weeks lag time. Results The analysis shows a yearly increase of 72–118 IPD cases due to influenza, which corresponds to 6–10% per year or 12–20% per influenza season. Also, a lag time of one to three weeks appears to be of significant importance in the relation between IPD and influenza. Conclusion This epidemiological study confirms the association between influenza and IPD. Furthermore, negative binomial regression models can be used to calculate number of excess cases of IPD, related to influenza.</p

The Swedish version of OMAS is a reliable and valid outcome measure for patients with ankle fractures

BACKGROUND: The aim of this study was to evaluate the test-retest reliability and the validity of the self-reported questionnaire Olerud-Molander Ankle Score (OMAS) in subjects after an ankle fracture. METHODS: When evaluating the test-retest reliability of the OMAS, 42 subjects surgically treated due to an ankle fracture participated 12 months after injury. OMAS was completed by the patients on two occasions at one to two weeks’ interval. Concurrent criterion validity was evaluated using the five subscales of the Foot and Ankle Outcome Score (FAOS) and global self-rating function (GSRF), which is a five-grade Likert scale with the alternatives: “very good”, “good”, “fair”, “poor”, “very poor”. Forty-six patients participated in the validation against FAOS, and for GSRF 105 patients participated at 6 months and 99 at 12 months. Uni-, bi- and trimalleolar fractures were all included and both non-rigid and rigid surgical techniques were used. All fractures healed without complications. Before analysis of the results the five groups according to GSRF were reduced to three: “good”, “fair” and “poor”. Test-retest reliability was assessed using Spearman’s rank correlation, the intraclass correlation coefficient (ICC), the standard error of measurement (SEM and SEM%) and the smallest real difference (SRD and SRD%). The Cronbach’s alpha score and validity versus FAOS was assessed using Spearman’s rank correlation and validity versus GSRF using the Kruskal-Wallis Test and the Mann–Whitney U-Test as ad hoc analyses. RESULTS: The test-retest reliability correlation coefficient obtained was rho = 0.95 and ICC = 0.94. The SEM was 4.4 points and SEM% 5.8% and should be interpreted as the smallest change that indicates a real change of clinical interest for a group of subjects. The SRD was 12 points and SRD% 15.8% and should be interpreted as the smallest change that indicates a real change of clinical interest for a single subject. The correlation coefficients versus the five subscales of FAOS ranged from rho = 0.80 to 0.86. There were significant differences between GSRF groups “good”, “fair” and “poor” (p < 0.001) at both the six-month and the 12-month follow-up. The internal consistency for the OMAS was 0.76. The effect size between results from 6-month and 12-month follow-up turned out be 0.44 and should be considered as medium. CONCLUSION: The results showed that the test-retest reliability of the Swedish version of OMAS was very high in subjects after an ankle fracture and the standard error of measurement was low. Furthermore the OMAS was found to be valid using both the five subscales of FAOS and the GSRF. The OMAS can thus be used as an outcome measure after an ankle fracture

Nitric oxide from inflammatory origin impairs neural stem cell proliferation by inhibiting epidermal growth factor receptor signaling

Neuroinflammation is characterized by activation of microglial cells, followed by production of nitric oxide (NO), which may have different outcomes on neurogenesis, favoring or inhibiting this process. In the present study, we investigated how the inflammatory mediator NO can affect proliferation of neural stem cells (NSCs), and explored possible mechanisms underlying this effect. We investigated which mechanisms are involved in the regulation of NSC proliferation following treatment with an inflammatory stimulus (lipopolysaccharide plus IFN-gamma), using a culture system of subventricular zone (SVZ)-derived NSCs mixed with microglia cells obtained from wild-type mice (iNOS(+/+)) or from iNOS knockout mice (iNOS(-/-)). We found an impairment of NSC cell proliferation in iNOS(+/+) mixed cultures, which was not observed in iNOS(-/-) mixed cultures. Furthermore, the increased release of NO by activated iNOS(+/+) microglial cells decreased the activation of the ERK/MAPK signaling pathway, which was concomitant with an enhanced nitration of the EGF receptor. Preventing nitrogen reactive species formation with MnTBAP, a scavenger of peroxynitrite (ONOO-), or using the ONOO- degradation catalyst FeTMPyP cell proliferation and ERK signaling were restored to basal levels in iNOS(+/+) mixed cultures. Moreover, exposure to the NO donor NOC-18 (100 mu M), for 48 h, inhibited SVZ-derived NSC proliferation. Regarding the antiproliferative effect of NO, we found that NOC-18 caused the impairment of signaling through the ERK/MAPK pathway, which may be related to increased nitration of the EGF receptor in NSC. Using MnTBAP nitration was prevented, maintaining ERK signaling, rescuing NSC proliferation. We show that NO from inflammatory origin leads to a decreased function of the EGF receptor, which compromised proliferation of NSC. We also demonstrated that NO-mediated nitration of the EGF receptor caused a decrease in its phosphorylation, thus preventing regular proliferation signaling through the ERK/MAPK pathway.Foundation for Science and Technology, (FCT, Portugal); COMPETE; FEDER [PEst-C/SAU/LA0001/2013-2014, PEst-OE/EQB/LA0023/2013-2014, PTDC/SAU-NEU/102612/2008, PTDC/NEU-OSD/0473/2012]; FCT, Portugal [SERH/BPD/78901/2011, SERH/BD/38127/2007, SFRH/BD/77903/2011, SFRH/BD/79308/2011]info:eu-repo/semantics/publishedVersio

Differential Activity of the Combination of Vancomycin and Amikacin on Planktonic vs. Biofilm-Growing Staphylococcus aureus Bacteria in a Hollow Fiber Infection Model

Combining currently available antibiotics to optimize their use is a promising strategy to reduce treatment failures against biofilm-associated infections. Nevertheless, most assays of such combinations have been performed in vitro on planktonic bacteria exposed to constant concentrations of antibiotics over only 24 h and the synergistic effects obtained under these conditions do not necessarily predict the behavior of chronic clinical infections associated with biofilms. To improve the predictivity of in vitro combination assays for bacterial biofilms, we first adapted a previously described Hollow-fiber (HF) infection model by allowing a Staphylococcus aureus biofilm to form before drug exposure. We then mimicked different concentration profiles of amikacin and vancomycin, similar to the free plasma concentration profiles that would be observed in patients treated daily over 5 days. We assessed the ability of the two drugs, alone or in combination, to reduce planktonic and biofilm-embedded bacterial populations, and to prevent the selection of resistance within these populations. Although neither amikacin nor vancomycin exhibited any bactericidal activity on S. aureus in monotherapy, the combination had a synergistic effect and significantly reduced the planktonic bacterial population by -3.0 to -6.0 log10 CFU/mL. In parallel, no obvious advantage of the combination, as compared to amikacin alone, was demonstrated on biofilm-embedded bacteria for which the addition of vancomycin to amikacin only conferred a further maximum reduction of 0.3 log10 CFU/mL. No resistance to vancomycin was ever found whereas a few bacteria less-susceptible to amikacin were systematically detected before treatment. These resistant bacteria, which were rapidly amplified by exposure to amikacin alone, could be maintained at a low level in the biofilm population and even suppressed in the planktonic population by adding vancomycin. In conclusion, by adapting the HF model, we were able to demonstrate the different bactericidal activities of the vancomycin and amikacin combination on planktonic and biofilm-embedded bacterial populations, suggesting that, for biofilm-associated infections, the efficacy of this combination would not be much greater than with amikacin monotherapy. However, adding vancomycin could reduce possible resistance to amikacin and provide a relevant strategy to prevent the selection of antibiotic-resistant bacteria during treatments

The occurrence and characterization of Campylobacter jejuni and C. coli in organic pigs and their outdoor environment

The occurrence and species distribution of thermophilic Campylobacter was investigated in organic outdoor pigs. An increased exposure of outdoor pigs to C. jejuni from the environment may cause a shift from a normal dominance of C. coli to more C. jejuni, which may imply a concern of reduced food safety. Bacteriological methods for determination of Campylobacter excretion level were combined with colony-blot hybridization and real-time PCR for specific detection of C. jejuni in pigs. Campylobacter was isolated from pigs (n = 47), paddock environment (n = 126) and wildlife (n = 44), identified to species by real-time PCR and sub-typed by serotyping (Penner) and pulse-field gel electrophorsis (PFGE) genotyping. All pigs excreted Campylobacter (103–107 CFU g1 faeces) from the age of 8–13-weeks old. C. jejuni was found in 29% of pigs in three consecutive trials and always in minority to C. coli (0.3–46%). C. jejuni and C. coli were isolated from 10% and 29% of the environmental samples, respectively, while crow-birds and rats harboured C. jejuni. Individual pigs hosted several strains (up to nine serotypes). The paddock environment was contaminated with C. coli serotypes similar to pig isolates, while most of the C. jejuni serotypes differed. C. jejuni isolates of different origin comprised few similar serotypes, just one identical genotype was common between pigs, environment and birds. In conclusion, the occurrence of C. jejuni varied considerably between the three groups of outdoor pigs. Furthermore, transfer of C. jejuni to the outdoor pigs from the nearby environment was not predominant according to the subtype dissimilarities of the obtained isolates

Heparin molecularly imprinted surfaces for the attenuation of complement activation in blood

Heparin-imprinted synthetic polymer surfaces with the ability to attenuate activation of both the complement and the coagulation system in whole blood were successfully produced. Imprinting was achieved using a template coated with heparin, a highly sulfated glycosaminoglycan known for its anticoagulant properties. The N,N'-diacryloylpiperazine-methacrylic acid copolymers were characterized using goniometry, AFM and XPS. The influence of the molecular imprinting process on morphology and template rebinding was demonstrated by radioligand binding assays. Surface hemocompatibility was evaluated using human whole blood without anticoagulants followed by measurement of complement activation markers C3a and sC5b-9 and platelet consumption as a surrogate coagulation activation marker. The observed low thrombogenicity of this copolymer combined with the attenuation of complement activation induced by the molecular imprint offer potential for the development of self-regulating surfaces with important potential clinical applications. We propose a mechanism for the observed phenomena based upon the recruitment of endogenous sulfated glycosaminoglycans with heparin-like activities

Are there new models of computation? Reply to Wegner and Eberbach

Wegner and Eberbach[Weg04b] have argued that there are fundamental limitations to Turing Machines as a foundation of computability and that these can be overcome by so-called superTuring models such as interaction machines, the [pi]calculus and the $-calculus. In this paper we contest Weger and Eberbach claims

TLR7-mediated skin inflammation remotely triggers chemokine expression and leukocyte accumulation in the brain

Background: The relationship between the brain and the immune system has become increasingly topical as, although it is immune-specialised, the CNS is not free from the influences of the immune system. Recent data indicate that peripheral immune stimulation can significantly affect the CNS. But the mechanisms underpinning this relationship remain unclear. The standard approach to understanding this relationship has relied on systemic immune activation using bacterial components, finding that immune mediators, such as cytokines, can have a significant effect on brain function and behaviour. More rarely have studies used disease models that are representative of human disorders. Methods: Here we use a well-characterised animal model of psoriasis-like skin inflammation—imiquimod—to investigate the effects of tissue-specific peripheral inflammation on the brain. We used full genome array, flow cytometry analysis of immune cell infiltration, doublecortin staining for neural precursor cells and a behavioural read-out exploiting natural burrowing behaviour. Results: We found that a number of genes are upregulated in the brain following treatment, amongst which is a subset of inflammatory chemokines (CCL3, CCL5, CCL9, CXCL10, CXCL13, CXCL16 and CCR5). Strikingly, this model induced the infiltration of a number of immune cell subsets into the brain parenchyma, including T cells, NK cells and myeloid cells, along with a reduction in neurogenesis and a suppression of burrowing activity. Conclusions: These findings demonstrate that cutaneous, peripheral immune stimulation is associated with significant leukocyte infiltration into the brain and suggest that chemokines may be amongst the key mediators driving this response