Comparative in vitro activities of trovafloxacin (CP-99,219) against 445 gram-positive isolates from patients with endocarditis and those with other bloodstream infections

The in vitro activity of trovafloxacin (CP-99,219), a new fluoroquinolone, was compared with the in vitro activities of other commonly used quinolones and other antimicrobial agents against 445 gram-positive microorganisms isolated between 1986 and 1995 from patients with endocarditis and those with other bloodstream infections. The MICs at which 90% of the isolates are inhibited (MIC90) of trovafloxacin for methicillin-susceptible staphylococci, viridans group streptococci, and enterococci were 0.06, 0.25, and 0.5 mg/liter, respectively. The MIC90 of trovafloxacin for vancomycin-resistant enterococci as well as for methicillin-resistant Staphylococcus aureus and methicillin-susceptible and ciprofloxacin-resistant S. aureus, isolated from sources other than blood, was 1 mg/liter. For the quinolones the rank order of activity was trovafloxacin > sparfloxacin > ciprofloxacin = ofloxacin > pefloxacin. Depending on the species tested, trovafloxacin was 4- to 64-fold more active than ciprofloxacin. Further experimental and in vivo studies are warranted to evaluate the efficacy of trovafloxacin in the treatment of bacterial endocarditis and other infections caused by gram-positive organisms

Technologies for restricting mould growth on baled silage

End of project reportSilage is made on approximately 86% of Irish farms, and 85% of these make some baled silage. Baled silage is particularly important as the primary silage making, storage and feeding system on many beef and smaller sized farms, but is also employed as a secondary system (often associated with facilitating grazing management during mid-summer) on many dairy and larger sized farms (O’Kiely et al., 2002). Previous surveys on farms indicated that the extent of visible fungal growth on baled silage was sometimes quite large, and could be a cause for concern. Whereas some improvements could come from applying existing knowledge and technologies, the circumstances surrounding the making and storage of baled silage suggested that environmental conditions within the bale differed from those in conventional silos, and that further knowledge was required in order to arrive at a secure set of recommendations for baled silage systems. This report deals with the final in a series (O’Kiely et al., 1999; O’Kiely et al., 2002) of three consecutive research projects investigating numerous aspect of the science and technology of baled silage. The success of each depended on extensive, integrated collaboration between the Teagasc research centres at Grange and Oak Park, and with University College Dublin. As the series progressed the multidisciplinary team needed to underpin the programme expanded, and this greatly improved the amount and detail of the research undertaken. The major objective of the project recorded in this report was to develop technologies to improve the “hygienic value” of baled silage

Phase I/II Clinical Trial-Based Early Economic Evaluation of Acalabrutinib for Relapsed Chronic Lymphocytic Leukaemia

Objectives: The objective of this study was to construct an early economic evaluation for acalabrutinib for relapsed chronic lymphocytic leukaemia (CLL) to assist early reimbursement decision making. Scenarios were assessed to find the relative impact of critical parameters on incremental costs and quality-adjusted life-years (QALYs). Methods: A partitioned survival model was constructed comparing acalabrutinib and ibrutinib from a UK national health service perspective. This model included states for progression-free survival (PFS), post-progression survival (PPS) and death. PFS and overall survival (OS) were parametrically extrapolated from ibrutinib publications and a preliminary hazard ratio based on phase I/II data was applied for acalabrutinib. Deterministic and probabilistic sensitivity analyses were performed, and 1296 scenarios were assessed. Results: The base-case inc

The Application and Implications of Novel Deterministic Sensitivity Analysis Methods

Deterministic sensitivity analyses (DSA) remain important to interpret the effect of uncertainties in individual parameters on results of cost-effectiveness analyses. Classic DSA methodologies may lead to wrong conclusions due to a lack of or misleading information regarding marginal effects, non-linearity, likelihood and correlations. In addition, tornado diagrams are misleading in some situations. Recent advances in DSA methods have the potential to provide decision makers with more reliable information regarding the effects of uncertainties in individual parameters. This practical application discusses advances to classic DSA methods and their implications. Three methods are discussed: stepwise DSA, distributional DSA and probabilistic DSA. For each method, the technical specifications, options for presenting results, and its implications for decision making are discussed. Options for visualizing DSA results in incremental cost-effectiveness ratios and in incremental net benefits are presented. The use of stepwise DSA increases interpretability of marginal effects and non-linearities in the model, which is especially relevant when arbitrary ranges are implemented. Using the probability distribution of each parameter in distributional DSA provides insight on the likelihood of model outcomes while probabilistic DSA also includes the effects of correlations between parameters. Probabilistic DSA, preferably expressed in incremental net benefit, is the most appropriate method for providing insight on the effect of uncertainty in individual parameters on the estimate of cost effectiveness. However, the opportunities provided by probabilistic DSA may not always be needed for decision making. Other DSA methods, in particular distributional DSA, can sometimes be sufficient depending on model features. Decision makers must determine to which extent they will accept and implement these new and improved DSA methodologies and adjust guidelines accordingly

Bubble Entrainment, Spray and Splashing at Hydraulic Jumps

The sudden transition from a high-velocity, supercritical open channel flow into a slow-moving sub-critical flow is a hydraulic jump. Such a flow is characterised by a sudden rise of the free-surface, with some strong energy dissipation and air entrainment, waves and spray. New two-phase flow measurements were performed in the developing flow region using a large-size facility operating at large Reynolds numbers. The experimental results demonstrated the complexity of the flow with a developing mixing layer in which entrained bubbles are advected in a high shear stress flow. The relationship between bubble count rates and void fractions was non-unique in the shear zone, supporting earlier observations of some form of double diffusion process between momentum and air bubbles. In the upper region, the flow consisted primarily of water drops and packets surrounded by air. Visually significant pray and splashing were significant above the jump roller. The present study is the first comprehensive study detailing the two-phase flow properties of both the bubbly and spray regions of hydraulic jumps, a first step towards understanding the interactions between bubble entrainment and droplet ejection processes

Development of a SERS strategy to overcome the nanoparticle stabilisation effect in serum-containing samples: Application to the quantification of dopamine in the culture medium of PC-12 cells

The analysis of serum samples by surface-enhanced Raman spectroscopy (SERS) has gained ground over the last years. However, the stabilisation of colloids by the proteins contained in these samples has restricted their use in common practice, unless antibodies or aptamers are used. Therefore, this work was dedicated to the development of a SERS methodology allowing the analysis of serum samples in a simple and easy-to-implement way. This approach was based on the pre-aggregation of the colloid with a salt solution. Gold nanoparticles (AuNPs) were used as the SERS substrate and, owing to its physiopathological importance, dopamine was chosen as a model to implement the SERS approach. The presence of this neurotransmitter could be determined in the concentration range 0.5 to 50 ppm (2.64 – 264 μM) in the culture medium of PC-12 cells, with a R2 of 0.9874, and even at lower concentrations (0.25 ppm, 1.32 μM) in another matrix containing fewer proteins. Moreover, the effect of calcium and potassium on the dopamine exocytosis from PC-12 cells was studied. Calcium was shown to have a predominant and dose-dependent effect. Finally, PC-12 cells were exposed to dexamethasone in order to increase their biosynthesis and release of dopamine. This increase was monitored with the developed SERS approach

On the selection of AGN neutrino source candidates for a source stacking analysis with neutrino telescopes

The sensitivity of a search for sources of TeV neutrinos can be improved by grouping potential sources together into generic classes in a procedure that is known as source stacking. In this paper, we define catalogs of Active Galactic Nuclei (AGN) and use them to perform a source stacking analysis. The grouping of AGN into classes is done in two steps: first, AGN classes are defined, then, sources to be stacked are selected assuming that a potential neutrino flux is linearly correlated with the photon luminosity in a certain energy band (radio, IR, optical, keV, GeV, TeV). Lacking any secure detailed knowledge on neutrino production in AGN, this correlation is motivated by hadronic AGN models, as briefly reviewed in this paper. The source stacking search for neutrinos from generic AGN classes is illustrated using the data collected by the AMANDA-II high energy neutrino detector during the year 2000. No significant excess for any of the suggested groups was found.Comment: 43 pages, 12 figures, accepted by Astroparticle Physic

Ebstein's anomaly may be caused by mutations in the sarcomere protein gene MYH7

Ebstein's anomaly is a rare congenital heart malformation characterised by adherence of the septal and posterior leaflets of the tricuspid valve to the underlying myocardium. Associated abnormalities of left ventricular morphology and function including left ventricular noncompaction (LVNC) have been observed. An association between Ebstein's anomaly with LVNC and mutations in the sarcomeric protein gene MYH7, encoding β -myosin heavy chain, has been shown by recent studies. This might represent a specific subtype of Ebstein's anomaly with a Mendelian inheritance pattern. In this review we discuss the association of MYH7 mutations with Ebstein's anomaly and LVNC and its implications for the clinical care for patients and their family members

Search for Neutrino-Induced Cascades with AMANDA

We report on a search for electro-magnetic and/or hadronic showers (cascades) induced by high energy neutrinos in the data collected with the AMANDA II detector during the year 2000. The observed event rates are consistent with the expectations for atmospheric neutrinos and muons. We place upper limits on a diffuse flux of extraterrestrial electron, tau and muon neutrinos. A flux of neutrinos with a spectrum $\Phi \propto E^{-2}$ which consists of an equal mix of all flavors, is limited to $E^2 \Phi(E)=8.6 x 10^{-7} GeV/(cm^{2} s sr)$ at a 90% confidence level for a neutrino energy range 50 TeV to 5 PeV. We present bounds for specific extraterrestrial neutrino flux predictions. Several of these models are ruled out.Comment: 18 pages, 12 figure

New results from the Antarctic Muon And Neutrino Detector Array

We present recent results from the Antarctic Muon And Neutrino Detector Array (AMANDA) on searches for high-energy neutrinos of extraterrestrial origin. We have searched for a diffuse flux of neutrinos, neutrino point sources and neutrinos from GRBs and from WIMP annihilations in the Sun or the center of the Earth. We also present a preliminary result on the first energy spectrum above a few TeV for atmospheric neutrinos.Comment: 8 pages, 8 figures, to be published in Nuclear Physics B (Proceedings Supplement): Proceedings of the XXIst International Conference on Neutrino Physics and Astrophysics, Paris, June 14-19, 200