The IT framework of the European Archive of Historical Earthquake Data (AHEAD)

The European Archive of Historical EArthquake Data (AHEAD) has been developed in the frame of the EC project NERIES and maintained in the frame of the EC project SHARE.AHEAD makes available on the web the result of a networked historical earthquake data research, formalised in terms of studies (papers, reports, macroseismic data points, etc). It provides an updated wealth of data that are unique for many European events in the time-window 1000-1963.A series of IT solutions have been developed in order to support both the research and the networking activities carried out within the building process of AHEAD. The resulting framework is an equally balanced effort in both the back-end and front-end design and implementation, a key feature in a research approach very much human-centred, where the quantity of data is small if compared to terabytes of instrumental data.AHEAD is composed of five mutually dependent data-components: 1) the “Digital Library”, where all the historical earthquake studies are stored and described by bibliographical metadata, 2) the “Consensus Earthquake Inventory”, where the relevant macroseismic data (event date, epicentral area, number of macroseismic data-point, maximum observed intensity) are extrapolated, the best available information are selected and fake earthquakes are highlighted, 3) the “European Macroseismic Database”, where all the available macroseismic data-points (MDPs) are stored, 4) the “Parameters Laboratory”, where earthquakes parameterisation methods are applied to MDPs in order to obtain epicentral locations and magnitudes and 5) the “European Earthquake Catalogue”.The presentation will demonstrate the adopted IT solutions separately for the back-end and the front-end, both for the access-restricted website and the general-purpose implementation designed to be included in the “Earthquake Data Portal”, developed within the EC project NERIES, which targets a much broader scientific community

Clinical application of microsampling versus conventional sampling techniques in the quantitative bioanalysis of antibiotics: a systematic review

Conventional sampling techniques for clinical pharmacokinetic studies often require the removal of large blood volumes from patients. This can result in a physiological or emotional burden, particularly for neonates or pediatric patients. Antibiotic pharmacokinetic studies are typically performed on healthy adults or general ward patients. These may not account for alterations to a patient's pathophysiology and can lead to suboptimal treatment. Microsampling offers an important opportunity for clinical pharmacokinetic studies in vulnerable patient populations, where smaller sample volumes can be collected. This systematic review provides a description of currently available microsampling techniques and an overview of studies reporting the quantitation and validation of antibiotics using microsampling. A comparison of microsampling to conventional sampling in clinical studies is included

Analysis of capillary microsamples obtained from a skin-prick to measure vancomycin concentrations as a valid alternative to conventional sampling: a bridging study

A bridging study is presented to investigate the applicability of measuring vancomycin concentrations obtained by finger-prick. A total of 25 paired plasma samples, collected from finger prick as capillary microsampling and arterial plasma samples collected from an indwelling cannula as conventional sampling, were obtained from critically ill patients receiving vancomycin. The maximum concentration (C) and the minimum concentration (C) measured were 66.2 mg/L and 29.7 mg/L for capillary microsampling and 78.9 mg/L, 25.6 mg/L for conventional sampling, respectively. The area under the concentration-time curve from 0 to 6 h (AUC) ranged between 94.8 and 269 mg/L.h for capillary microsampling and from 106 and 303 mg/L.h for conventional sampling. The comparative study conducted was assessed using three different statistical approaches: Bland-Altman and Passing-Bablok regression analyses and the USFDA criterion for the incurred sample reanalysis. The results of this analysis revealed no significant bias and a strong correlation between both sampling methods, with 95% of the calculated concentrations from the paired plasma samples laying within 20% of difference of the mean. This bridging study verifies that capillary microsampling may serve as an alternative to conventional sampling techniques to support clinical applications for measuring vancomycin concentrations in plasma

A UHPLC–MS/MS method for the simultaneous determination of piperacillin and tazobactam in plasma (total and unbound), urine and renal replacement therapy effluent

Piperacillin-tazobactam is a beta-lactam/beta-lactamase combination antibiotic used in patients with moderate to severe infection. Dosing of piperacillin-tazobactam requires an understanding of this patient group to maximise the effectiveness of this antibiotic and limit a further emergence of resistant pathogens. This is the first method that measures piperacillin and tazobactam simultaneously, across this range of clinically-relevant biological matrices. The calibration line was linear across the concentration range of 0.5–500 μg/mL for piperacillin and 0.625–62.5 μg/mL for tazobactam. All validation testing for matrix effects, precision and accuracy, specificity and stability were within 15%. A calibration equivalence study was performed to investigate the suitability of applying calibration curves prepared in an alternative matrix, with a mean bias of −10.8% identified for the application of a calibration line prepared for tazobactam in plasma only. Bias for all other calibration lines prepared in alternate matrices was within the 5% acceptance criteria. The method was successfully applied to a pharmacokinetic study of a critically ill patient receiving renal replacement therapy, with the results included

A validated UHPLC-MS/MS method for the measurement of riluzole in plasma and myocardial tissue samples

Through blocking the cardiac persistent sodium current, riluzole has the potential to prevent myocardial damage post cardiac bypass surgery. A sensitive UHPLC–MS/MS method was developed and validated for quantitation of riluzole and 5-methoxypsoralen in human plasma and myocardial tissue homogenate using a liquid–liquid extraction with dichloromethane. The chromatographic separation was achieved using Shimadzu Shim-pack XR-ODS III, 2.0 × 50 mm, 1.6 μm column with a gradient mobile phase comprising methanol and ammonium acetate buffer pH 3.6 in purified water. The analyte and internal standard were separated within 3.5 min. Riluzole quantitation was achieved using the mass transitions of 235–138 for riluzole and 217–156 for 5-methoxypsoralen. The method was linear for riluzole plasma concentrations from 0.2 to 500 ng/mL and myocardial tissue homogenate concentrations from 0.2 to 100 ng/mL. The method developed was successfully applied to a clinical study for patients receiving riluzole while undergoing cardiac bypass surgery.J.A. Roberts is a recipient of an Australian National Health and MedicalResearch Council Fellowship (APP1048652). The authors acknowledgefunding from the Australian National Health and Medical ResearchCouncil for Project Grants (APP1044941, APP1062040) and Centreof Research Excellence (APP1099452

Pharmacodynamic evaluation of plasma and epithelial lining fluid exposures of amikacin against in a dynamic hollow-fibre infection model

Given that aminoglycosides, such as amikacin, may be used for multi-drug resistant infections, optimization of therapy is paramount for improved treatment outcomes. This study aims to investigate the pharmacodynamics of different simulated intravenous amikacin doses on susceptible to inform ventilator-associated pneumonia and sepsis treatment choices.A hollow-fibre infection model with two isolates (MIC 2 and 8 mg/L) with an initial inoculum ∼10 colony-forming unit/mL was used to test different amikacin dosing regimens. Three regimens (15, 25 and 50 mg/kg) simulating a blood exposure and a 30 mg/kg regimen simulating the epithelial lining fluid (ELF) for potential respiratory tract infection were tested. Data were described using a semi-mechanistic pharmacokinetic/pharmacodynamic (PK/PD) model. Whole genome sequencing was used to identify mutations associated with resistance emergence.While bacterial density was reduced by >6-logs within the first 12 h in simulated blood exposures, following this initial bacterial kill, there was amplification of a resistant sub-population with ribosomal mutations that were likely mediating amikacin resistance. No appreciable bacterial killing occurred with subsequent doses. There was less