Virtual unfolding of folded papyri

The historical importance of ancient manuscripts is unique since they provide information about the heritage of ancient cultures. Often texts are hidden in rolled or folded documents. Due to recent improvements in sensitivity and resolution, spectacular disclosures of rolled hidden texts were possible by X-ray tomography. However, revealing text on folded manuscripts is even more challenging. Manual unfolding is often too risky in view of the fragile condition of fragments, as it can lead to the total loss of the document. X-ray tomography allows for virtual unfolding and enables non-destructive access to hidden texts. We have recently demonstrated the procedure and tested unfolding algorithms on a mockup sample. Here, we present results on unfolding ancient papyrus packages from the papyrus collection of the Musée du Louvre, among them objects folded along approximately orthogonal folding lines. In one of the packages, the first identification of a word was achieved, the Coptic word for “Lord”

Susceptibility breakpoints and target values for therapeutic drug monitoring of voriconazole and Aspergillus fumigatus in an in vitro pharmacokinetic/pharmacodynamic model

Although voriconazole reached the bedside 10 years ago and became the standard care in the treatment of invasive aspergillosis, reliable clinical breakpoints are still in high demand. Moreover, this has increased due to the recent emergence of azole resistance. Four clinical wild-type and non-wild-type A. fumigatus isolates with voriconazole CLSI MICs in the range of 0.125-2 mg/L were tested in an in vitro pharmacokinetic (PK)/pharmacodynamic (PD) model. Mouse PK was simulated and in vitro data were compared with in vivo outcome. Human PK was simulated and susceptibility breakpoints and trough levels required for optimal treatment were determined for the CLSI and EUCAST methods after 48 h and the gradient concentration MIC test strip (MTS) method after 24 h using the in vitro PK/PD relationship and Monte Carlo simulation. The in vitro PK/PD target (95% CI) associated with 50% of the maximal antifungal activity (EC50) was 28.61 (16.18-50.61), close to the in vivo EC50 of 14.67 (9.31-21.58) fAUC(0-24)/CLSI MIC. When human PK was simulated, the EC50 was 24.7 (17.9-35.6) fAUC(0-12)/CLSI MIC and it was associated with 6 week survival in clinical studies of invasive pulmonary aspergillosis. Target attainment rates were a parts per thousand currency sign5% (0%-24%), 42% (16%-58%), 68% (54%-75%) and a parts per thousand yen79% (73%-86%) for isolates with CLSI MICs a parts per thousand yen2, 1, 0.5 and a parts per thousand currency sign0.25 mg/L, respectively. A trough/CLSI MIC ratio of 2 was required for optimal treatment. The susceptible/intermediate/resistant breakpoints were determined to be 0.25/0.5-1/2 mg/L for CLSI, 0.5/1-2/4 mg/L for EUCAST and 0.25/0.375-1/1.5 mg/L for MTS. These susceptibility breakpoints and target values for therapeutic drug monitoring could be used to optimize voriconazole therapy against A. fumigatus

Susceptibility breakpoints and target values for therapeutic drug monitoring of voriconazole and Aspergillus fumigatus in an in vitro pharmacokinetic/pharmacodynamic model

Background Although voriconazole reached the bedside 10 years ago and became the standard care in the treatment of invasive aspergillosis, reliable clinical breakpoints are still in high demand. Moreover, this has increased due to the recent emergence of azole resistance. Methods Four clinical wild-type and non-wild-type A. fumigatus isolates with voriconazole CLSI MICs in the range of 0.125-2 mg/L were tested in an in vitro pharmacokinetic (PK)/pharmacodynamic (PD) model. Mouse PK was simulated and in vitro data were compared with in vivo outcome. Human PK was simulated and susceptibility breakpoints and trough levels required for optimal treatment were determined for the CLSI and EUCAST methods after 48 h and the gradient concentration MIC test strip (MTS) method after 24 h using the in vitro PK/PD relationship and Monte Carlo simulation. Results The in vitro PK/PD target (95% CI) associated with 50% of the maximal antifungal activity (EC50) was 28.61 (16.18-50.61), close to the in vivo EC50 of 14.67 (9.31-21.58) fAUC0-24/CLSI MIC. When human PK was simulated, the EC50 was 24.7 (17.9-35.6) fAUC0-12/CLSI MIC and it was associated with 6 week survival in clinical studies of invasive pulmonary aspergillosis. Target attainment rates were ≤5% (0%-24%), 42% (16%-58%), 68% (54%-75%) and ≥79% (73%-86%) for isolates with CLSI MICs ≥2, 1, 0.5 and ≤0.25 mg/L, respectively. A trough/CLSI MIC ratio of 2 was required for optimal treatment. The susceptible/intermediate/resistant breakpoints were determined to be 0.25/0.5-1/2 mg/L for CLSI, 0.5/1-2/4 mg/L for EUCAST and 0.25/0.375-1/1.5 mg/L for MTS. Conclusions These susceptibility breakpoints and target values for therapeutic drug monitoring could be used to optimize voriconazole therapy against A. fumigatus. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved

Susceptibility breakpoints and target values for therapeutic drug monitoring of voriconazole and Aspergillus fumigatus in an in vitro pharmacokinetic/pharmacodynamic model--authors' response

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Emissions of organic pollutants from traffic and roads: Priority pollutants selection and substance flow analysis

A large number of organic pollutants (OPs) emitted from vehicles and traffic-related activities exhibit environmental persistence and a tendency to bioaccumulate, and may have detrimental long-term effects on aquatic life. The aim of the study was to establish a list of significant sources of OPs occurring in road runoff, identify the OPs emitted from these sources, select a number of priority pollutants (PP), and estimate the quantity of PPs emitted in a road environment case study using substance flow analysis (SFA). The priority pollutants included in the SFA were selected from a list of approximately 1100 compounds found after comprehensive screening, including literature and database searches, expert judgments, the Ranking and Identification of Chemical Hazards method, and chemical analysis of sediments. The results showed the following priority order: polycyclic aromatic hydrocarbons (PAHs)> alkanes C20-C40 > alkylphenols > phthalates > aldehydes > phenolic antioxidants > bisphenol A > oxygenated-PAHs > naphtha C5-C12 > amides > amines. Among these, PAHs were chosen for a SFA, which was performed for a highway case study area in Gothenburg (Sweden). The SFA showed that the main sources of PAHs emitted in the area were vehicle exhaust gases, followed by tyre wear, motor lubricant oils, road surface wear, and brake linings. Only 2-6% of the total 5.8-29kg annually emitted PAHs/ha ended up in the stormwater sewer system. The measured PAH loads were found in much smaller amounts than the calculated loads and the outflow to stormwater contained much more of the hazardous PAHs than the total loads emitted in the catchment area

Absorption edge sensitive radiography and tomography of Egyptian Papyri

International audienceIn the Egyptian Museum and Papyrus Collection, Berlin, a multitude of papyrus manuscripts are stored. Papyri found on Elephantine island are of special interest. No other settlement in Egypt has been so well documented through texts over four millennia. However, 80% of the Elephantine texts are yet to be documented and published. As part of the "Elephantine" project, funded by an ERC starting grant, we attempt to gain access to hidden text. Most of the fragments are very fragile, deformed, with some rolled or folded. Papyri from the Old and Middle Kingdom were typically written with carbon ink. Consequently, these fragments show no absorption sensitivity for hard X-rays. Also, other inks have been used in those times. If small traces of high-Z elements, like Fe or Pb, are found, absorption may be sensitive enough for radiography and tomography to distinguish between writing and base material. We sorted out suitable fragments and papyrus packages by X-ray fluorescence mapping. When promising high-Z elements were detected, absorption tomography was applied using micro-CT laboratory systems or synchrotron X-rays at the BAMline at BESSY II. The sensitivity can be enhanced by element-sensitive absorption edge imaging, where transmission data taken above and below the edge are compared. This technique was applied at the absorption edges of the elements known to be used as ink and pigment material-Iron, Antimony and Lead. These X-ray results were complemented by Fourier-transform infrared spectroscopy (FT-IR) measurements showing that the lead is found in the form of lead carboxylate. In the future, the presented methodology will be applied to folded or rolled papyri, allowing for analysis of the text without manually opening the fragments

Successful therapy of Candida pulcherrima fungemia in a premature newborn with liposomal amphotericin B and micafungin

New Candida species may cause bloodstream infections challenging current therapeutic approaches because of unpredictable susceptibility and virulence. In the present report, we describe a fungemia case due to Candida pulcherrima in a premature neonate. After full in vitro diagnostic workup, the neonate was successfully treated with liposomal amphotericin B and micafungin achieving rapid fungal eradication from blood. © 2016 The Author