Cost-Effectiveness Analyses of an Absorbable Antibacterial Envelope for Use in Patients at Increased Risk of Cardiac Implantable Electronic Device Infection in Germany, Italy, and England

Objectives: To model the cost-effectiveness of the TYRX Absorbable Antibacterial Envelope when used in patients at increased risk of cardiac implantable electronic device (CIED) infection in the context of 3 European healthcare systems: Germany, Italy, and England. Methods: A decision tree model with a lifetime horizon was populated using data from the Worldwide Randomized Antibiotic Envelope Infection Prevention Trial, a large multicenter randomized controlled trial. Use of the antibacterial envelope adjunctive to standard of care was compared to standard of care infection prevention alone. Patients in the model were divided into subgroups based on presence of factors known to increase infection risk. Results: The antibacterial envelope had the most favorable cost-effectiveness profile when patients had previously experienced CIED infection, had a history of immunosuppressive therapy, or had a Prevention of Arrhythmia Device Infection Trial (PADIT) score indicating high risk of infection (scores ≥6) at cost-effectiveness thresholds of €50 000 in Germany (assumed in the absence of an official threshold), €40 000 in Italy, and £30 000 in England. Probabilistic sensitivity analysis indicated that the antibacterial envelope was likely to be cost-effective in patients with other risk factors (including replacement of high power CIEDs, generator replacement with lead modification, and PADIT scores indicating intermediate risk of infection) when used with some device types and in some countries. Conclusions: The absorbable antibacterial envelope was associated with cost-effectiveness ratios below European benchmarks in selected patients at increased risk of infection, suggesting the envelope provides value for European healthcare systems by reducing CIED infections

Characterisation of the Fusarium graminearum-Wheat Floral Interaction

Fusarium Ear Blight is a destructive fungal disease of cereals including wheat and can contaminate the crop with various trichothecene mycotoxins. This investigation has produced a new β-glucuronidase (GUS) reporter strain that facilitates the quick and easy assessment of plant infection. The constitutively expressed gpdA:GUS strain of Fusarium graminearum was used to quantify the overall colonisation pattern. Histochemical and biochemical approaches confirmed, in susceptible wheat ear infections, the presence of a substantial phase of symptomless fungal growth. Separate analyses demonstrated that there was a reduction in the quantity of physiologically active hyphae as the wheat ear infection proceeded. A simplified linear system of rachis infection was then utilised to evaluate the expression of several TRI genes by RT-qPCR. Fungal gene expression at the advancing front of symptomless infection was compared with the origin of infection in the rachis. This revealed that TRI gene expression was maximal at the advancing front and supports the hypothesis that the mycotoxin deoxynivalenol plays a role in inhibiting plant defences in advance of the invading intercellular hyphae. This study has also demonstrated that there are transcriptional differences between the various phases of fungal infection and that these differences are maintained as the infection proceeds

Quantum dot loaded immunomicelles for tumor imaging

<p>Abstract</p> <p>Background</p> <p>Optical imaging is a promising method for the detection of tumors in animals, with speed and minimal invasiveness. We have previously developed a lipid coated quantum dot system that doubles the fluorescence of PEG-grafted quantum dots at half the dose. Here, we describe a tumor-targeted near infrared imaging agent composed of cancer-specific monoclonal anti-nucleosome antibody 2C5, coupled to quantum dot (QD)-containing polymeric micelles, prepared from a polyethylene glycol/phosphatidylethanolamine (PEG-PE) conjugate. Its production is simple and involves no special equipment. Its imaging potential is great since the fluorescence intensity in the tumor is twofold that of non-targeted QD-loaded PEG-PE micelles at one hour after injection.</p> <p>Methods</p> <p>Para-nitrophenol-containing (5%) PEG-PE quantum dot micelles were produced by the thin layer method. Following hydration, 2C5 antibody was attached to the PEG-PE micelles and the QD-micelles were purified using dialysis. 4T1 breast tumors were inoculated subcutaneously in the flank of the animals. A lung pseudometastatic B16F10 melanoma model was developed using tail vein injection. The contrast agents were injected via the tail vein and mice were depilated, anesthetized and imaged on a Kodak Image Station. Images were taken at one, two, and four hours and analyzed using a methodology that produces normalized signal-to-noise data. This allowed for the comparison between different subjects and time points. For the pseudometastatic model, lungs were removed and imaged <it>ex vivo </it>at one and twenty four hours.</p> <p>Results</p> <p>The contrast agent signal intensity at the tumor was double that of the passively targeted QD-micelles with equally fast and sharply contrasted images. With the side views of the animals only tumor is visible, while in the dorsal view internal organs including liver and kidney are visible. <it>Ex vivo </it>results demonstrated that the agent detects melanoma nodes in a lung pseudometastatic model after a 24 hours wash-out period, while at one hour, only a uniform signal is detected.</p> <p>Conclusions</p> <p>The targeted agent produces ultrabright tumor images and double the fluorescence intensity, as rapidly and at the same low dose as the passively targeted agents. It represents a development that may potentially serve to enhance early detection for metastases.</p

Istraživanje mehanizma toksičnosti anilina u eritrocitima

Strategies for the use of bio-indicators in the prediction of environmental damage should include mechanistic research. This study involves the relationship between the chemical structure and hemotoxic markers of aniline and its halogenated analogs. Aniline-induced methemoglobinemia, loss of circulating blood cells, blood stability, glutathione depletion and membrane cytoskeletal changes were assessed following exposure to phenylhydroxylamine (PHA), para-fluoro-, para-bromo-, and para-iodo in male Sprague-Dawley rats. Methemoglobin was determined spectrophotometrically at 635 nm. Erythrocyte depletion was investigated by loss of radioactivity in chromium-labeled red blood cells in vivo. Membrane proteins were analyzed by SDS-PAGE using red blood ghost cells treated with various aniline analogs. Results showed dose- and time-dependent changes in the induction of methemoglobin of up to 78 % with para-bromo PHA and 75 % with para-iodo PHA compared to 3 % to 5 % in control. Treated animals lost up to three times more blood from circulation compared to control within 14 days after treatment. Erythrocytes were more stable in buffer solution than in para-iodo-treated cells. Depletion of reduced glutathione in PHA and para-iodo-PHA treated red cells was also observed. Analysis of red cell skeletal membrane treated with para-iodo-PHA showed that protein band 2.1 became broader and band 2.2 diminished completely in some treatments. Dose- and time-dependent changes suggested the use of hemotoxic endpoints as potential biomarkers for assessing chemical and drug safetyStrategije primjene biopokazatelja za predviđanje štete u okolišu trebaju u obzir uzeti istraživanja mehanizama djelovanja. Ovo istraživanje propituje odnos između kemijske strukture i hemotoksičnih pokazatelja djelovanja anilina i njegovh halogeniranih analoga. Nakon izlaganja mužjaka štakora soja Sprague-Dawley para-fluoro-, para-bromo- i para-jodofenilhidroksilaminu, utvrđena je methemoglobinemija uzrokovana anilinom te pad broja krvnih stanica u krvotoku i stabilnosti krvi, gubitak glutationa i promjene na membrani stanice. Methemoglobin je određivan spektrofotometrijski na 635 nm. Pad broja eritrocita mjeren je in vivo s pomoću eritrocita obilježenih radioaktivnim kromom. Membranske su bjelančevine analizirane s pomoću SDS-PAGE, rabeći eritrocite bez hemoglobina (engl. ghost cells) kojima su dodani različiti analozi anilina. Nalazi upućuju na promjene indukcije methemoglobina ovisno o dozi i vremenu djelovanja do 78 % s para-bromo-fenilhidroksilaminom te do 75 % s para-jodofenilhidroksilaminom u usporedbi s 3 % do 5 % u kontrolnih uzoraka. U razdoblju od 14 dana nakon tretiranja izložene životinje izgubile su tri puta više krvi iz krvotoka od kontrolnih. Eritrociti su bili stabilniji u puferskoj otopini negoli u stanicama kojima je dodan para-jodofenilhidroksilamin. Zamijećen je i pad glutationa u eritrocitima kojima je dodan fenilhidroksilamin odnosno para-jodofenilhidroksilamin. Analizom membrane eritrocita kojima je dodan para-jodofenilhidroksilamin zamijećeno je da se u pojedinih obrada raširila proteinska vrpca 2.1, a potpuno smanjila proteinska vrpca 2.2. Zamijećene promjene uvjetovane dozom i vremenom upućuju na primjenu hemotoksičnih parametara kao mogućih biopokazatelja u procjeni sigurnosti lijeka odnosno kemikalije

Comparison between experiment and molecular dynamic simulation of spallation by ultra-short laser shock driven on micrometric Tantalum targets

International audienc

two-dimensional investigation of laser shock induced spallation in sub-picosecond regime

International audienc

Two-dimensional investigation of laser shock induced spallation in sub-picosecond regime

Shock wave propagation and spallation within materials submitted to laser shock have been investigated for roughly two decades. The characteristic durations studied were mainly in the nanosecond range. However, with the latest laser technologies evolution, one can access shorter regimes in durations, going below the picosecond. In the continuity of the studies performed in nanosecond regime, experiments have shown the possibility to obtain reproducible spallation at the micrometric range (spall thicknesses below 10 μm). The spalls observed show a planar rupture surface. The results obtained by post-mortem observation show that the spall thickness is thinner if the target thickness is reduced. The study is orientated to the two-dimensional damage which is caused by edge effects. This phenomenon is due to the limited loaded surface and the laser space repartition. These effects are particularly visible through the spall diameter. Shots on aluminum targets of various thicknesses with different laser spot diameters show the thicker the target, the smaller the diameter. This reduction is caused by the edge effects development which alters the tension state space repartition responsible of spallation. These data combined with a two-dimensional simulation can inform about the material dynamic damage behaviour

Implications of Differential Age Distribution of Disease-Associated Meningococcal Lineages for Vaccine Development

New vaccines targeting meningococci expressing serogroup B polysaccharide have been developed, with some being licensed in Europe. Coverage depends on the distribution of disease-associated genotypes, which may vary by age. It is well established that a small number of hyperinvasive lineages account for most disease, and these lineages are associated with particular antigens, including vaccine candidates. A collection of 4,048 representative meningococcal disease isolates from 18 European countries, collected over a 3-year period, were characterized by multilocus sequence typing (MLST). Age data were available for 3,147 isolates. The proportions of hyperinvasive lineages, identified as particular clonal complexes (ccs) by MLST, differed among age groups. Subjects <1 year of age experienced lower risk of sequence type 11 (ST-11) cc, ST-32 cc, and ST-269 cc disease and higher risk of disease due to unassigned STs, 1- to 4-year-olds experienced lower risk of ST-11 cc and ST-32 cc disease, 5- to 14-year-olds were less likely to experience ST-11 cc and ST-269 cc disease, and ≥25-year-olds were more likely to experience disease due to less common ccs and unassigned STs. Younger and older subjects were vulnerable to a more diverse set of genotypes, indicating the more clonal nature of genotypes affecting adolescents and young adults. Knowledge of temporal and spatial diversity and the dynamics of meningococcal populations is essential for disease control by vaccines, as coverage is lineage specific. The nonrandom age distribution of hyperinvasive lineages has consequences for the design and implementation of vaccines, as different variants, or perhaps targets, may be required for different age groups